by Charlotte Kilpatrick | Sep 18, 2024 | Technology |
PharmaJet announced in September 2024 that it has entered a long-term license and supply agreement with Scancell Holdings to use PharmaJet’s Stratis Intramuscular (IM) Needle-free System for the delivery of its advanced melanoma DNA vaccine. Through the agreement, Scancell will use Stratis for the clinical development and commercialisation of ImmunoBody, the advanced melanoma DNA vaccine. PharmaJet will receive development and regulatory milestone payments and royalties on net sales upon commercialisation.
Stratis
PharmaJet’s Stratis technology is a needle-free system for 0.5 ml intramuscular and subcutaneous injections that enhances the performance of nucleic acid vaccines and therapeutics. Stratis delivery has demonstrated the ability to enable “effective uptake” of the Scancell DNA melanoma vaccine; 60 patients across 15 clinical trial sites have received a total of 171 doses of SCIB1/iSCIB1+ through Stratis. This approach offers the “convenience of an off-the-shelf therapeutic cancer vaccine with the speed and enhanced patient experience of needle-free delivery”.
ImmunoBody vaccines
Scancell’s ImmuoBody vaccines are designed to generate “potent” T cell responses that provide a broad anti-tumour effect. They are DNA vaccines that encode a protein in antibody form, with the elements of the antibody that would normally bind to the target protein replaced with cancer antigen epitopes. ImmunoBody vaccine design features include:
- Epitopes that bind to MHC class I and MHC class II
- Retention of the Fc region of the protein, which targets activated dendritic cells via its specific receptor
However, Scancell highlights the “most important aspect” of the technology as the ability to initiate both direct and cross-presentation of epitopes to T cells. The “highest avidity T cell responses” are generated if different pathways are used to present the same epitope. In ImmunoBody, the DNA form is taken up and processed directly by dendritic cells and the protein form binds to the high affinity Fc receptor on dendritic cells, leading to cross-presentation.
Advancing innovation
Professor Lindy Durrant, Chief Executive Officer of Scancell, is pleased that PharmaJet delivery “works effectively” with the SCIB1/iSCIB1+ vaccines and offers a “well-received immunisation for patients”.
“Securing long term supply for the PharmaJet Stratis Needle-free Injection System is important to allow clinical and commercial development of iSCIB1+…Our ultimate goal for Scancell has been to deliver an off-the-shelf, safe, tolerable, effective therapy that can provide potent and durable anti-tumour responses for unresectable stage IV melanoma, which currently has a 5-year survival of 35%.”
PharmaJet’s Chief Scientific Officer, Nathalie Landry, looks forward to working with Scancell to “advance their innovation further in clinical development and commercialisation” with benefits for melanoma patients.
“The Scancell strategic partnership further solidifies PharmaJet’s commercial delivery platform as a leader in the delivery of nucleic acid vaccines and immunotherapies.”
For more on PharmaJet’s needle-free delivery technology, join us at the Congress in Barcelona next month. Don’t forget to subscribe to our weekly newsletters for regular vaccine updates.
by Charlotte Kilpatrick | Sep 18, 2024 | Technology |
MinervaX and Wacker Biotech announced a collaboration to manufacture active protein ingredients for MinervaX’s Group B Streptococcus (GBS) vaccine in September 2024. The vaccine candidate is a novel protein-only vaccine, based on fusions of “highly immunogenic and proactive protein domains” from selected GBS surface proteins. Wacker Biotech is to manufacture the active ingredients and perform technology transfer, process validation, and process characterisation activities for commercial manufacturing. The organisation will also perform key functions to ensure “stable commercial supply” at its Amsterdam site.
GBS
Group B Streptococcus (GBS) is a “leading cause” of neonatal and infant sepsis and meningitis. The highest incidence is in neonates and young infants up to 3 months old. Between 15% and 25% of the population are “spontaneously colonised” with GBS, but during pregnancy this carries the risk of transmitting the bacteria to the child in the womb, during birth, and/or during the first months of life. WHO emphasises the need for an effective maternal GBS vaccine to protect neonates and infants before they can elicit and effective immune response.
MinervaX identifies an “unmet medical need” as there is no “general implemented and fully protective preventative treatment” for GBS. Furthermore, older adults and adults with some co-morbidities are at increased risk of severe GBS infections. This population would also benefit from a prophylactic vaccine.
A protein approach
MinervaX has developed a novel protein-only vaccine based on fusions of “highly immunogenic and protective protein domains” from the Alpha-like protein family (AlpN). This approach is intended to deliver a vaccine with “broad coverage and protection”. The lead candidate, AlpN GBS, comprises two fusion proteins, each containing two AlpN-terminal domains: GBS-NN (containing RibN and AlpCn) and GBS-NN2 (containing Alp1N and Alp2/3N).
Two Phase II clinical trials of the maternal vaccine have been successfully completed, and MinervaX is preparing for Phase III trials in this indication. Data are “very positive”, with an “acceptable” safety profile in pregnant participants and their infants, and “high immunogenicity”.
Joining forces
Dr Per Fischer, CEO of MinervaX, commented that GBS “can be life-threatening for newborn babies” and is associated with “over half a million preterm births annually”. However, after €54 million financing last year, the team is advancing the development of their novel prophylactic vaccine “for the benefit of all populations at risk, worldwide”.
“Wacker Biotech is a robust manufacturing partner with a strong track record in late clinical and commercial supply and we look forward to collaborating with the team ahead of commencing Phase III studies.”
Managing Director of Wacker Biotech B.V in Amsterdam, Ronald Eulenberger, looks forward to bringing Wacker Biotech’s strengths to the collaboration.
“With our strong background in E. coli processes, process characterisation, and process validation experiences, we at Wacker Biotech are perfectly suited to support MinervaX with its ongoing programme for the prevention of invasive GBS disease.”
We look forward to hearing from MinervaX’s CSO, Dr Bengt Johansson Lindbom, on a panel exploring the role of vaccines and mAbs in neonatal sepsis prevention at the Congress in Barcelona next month. Get your tickets to join us there and don’t forget to subscribe to our weekly newsletters for the latest vaccine news.
by Charlotte Kilpatrick | Sep 17, 2024 | Technology |
Albert Einstein College of Medicine announced receipt of a five-year grant worth $14 million a year from the National Institute of Allergy and Infectious Diseases (NIAID). The grant is part of NIAID’s ReVAMPP (Research and Development of Vaccines and Monoclonal Antibodies for Pandemic Preparedness) Network. The funding will enable participation in a national effort to develop “plug-and-play” vaccines and antibody-based therapies against various emerging viruses. Albert Einstein College of Medicine will lead a consortium, called PROVIDENT (Prepositioning Optimised Strategies for Vaccines and Immunotherapies Against Diverse Emerging Infectious Threats).
PROVIDENT
The PROVIDENT consortium links 13 teams from academia, government, and industry on four projects to:
- Discover and analyse virus-host interactions and the molecular mechanisms involved in viral disease
- Design proteins to elicit antiviral immune responses and then evaluate and optimise those responses
- Create “road maps” for quick development of RNA vaccines against microbes with pandemic potential
- Map the antibody response observed in people infected with viruses for use in vaccine and therapeutic design
The project builds on NIAID’s 2021 Pandemic Preparedness Plan, which “leverages its broad research portfolio, long-standing expertise in product development, capacity to engage both domestic and international partners, and flexible infrastructure”. The plan addresses both “priority pathogens” and “prototype pathogens”.
Prototype pathogens will be PROVIDENT’s focus; these are “representative viruses” in families with potential to cause “significant human disease”. The research will concentrate on three virus families:
- Nairoviruses – transmitted by ticks
- Hantaviruses – borne by rodents and other small mammals
- Paramyxoviruses – borne by bats and other mammals
A sprint strategy
Dr Kartik Chandran, principal investigator on the grant, professor of microbiology and immunology, Gertrude and David Feinson Chair in Medicine, and Harold and Muriel Block Faculty Scholar in Virology, reflected on the importance of pandemic preparedness as revealed during COVID-19.
“One of the key lessons from the COVID pandemic is that having existing research on a viral family allows scientists to develop vaccines and therapeutics for a particular virus much more quickly. In our project, we plan to create a base of critical knowledge about a group of similar viruses and then – should a related ‘virus X’ pose a health threat – develop specific countermeasures as quickly as possible to save as many lives as possible.”
Dr Chandran explained that the researchers will select and study one or two prototype viruses from each family, developing countermeasures that will work against “as many viruses within that family as possible”.
“That strategy of quickly responding to an emerging virus with an approach and tools that have already been developed is what we mean by ‘plug and play’. A part of PROVIDENT’s strategy will be to carry out ‘sprints’ in which countermeasures that are developed for the prototype pathogens will be tested against other viruses in the same family to see how well they work and to improve them.”
The approach enabled faster development during the COVID-19 pandemic, and Dr Chandran emphasised the importance of coordinating efforts to “increase our odds of mounting a timely and effective response”. Dr Eva Mittler, research assistant professor and leader of a PROVIDENT component, warned that “we don’t know what virus will cause the next pandemic”.
“Recent outbreaks of mpox, Nipah virus, and Eastern equine encephalitis, among other viral infections, underscore the need for an even broader preparedness programme.”
To join your colleagues at the Congress in Barcelona next month and share perspectives on pandemic preparedness and innovative vaccine development, get your tickets now. Don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Sep 13, 2024 | Technology |
In September 2024, WHO announced that the MVA-BN vaccine, manufactured by Bavarian Nordic, is the first vaccine against mpox to be put on the prequalification list. This approval is “expected to facilitate timely and increased access” to the vaccine in “communities with urgent need” amid the outbreak of mpox. The prequalification is based on information submitted by Bavarian Nordic and reviewed by the European Medicines Agency.
Recommended for use
WHO’s Strategic Advisory Group of Experts (SAGE) on Immunisation recommended the use of MVA-BN in an mpox outbreak context for persons at high risk of exposure. It can be administered in over-18s in two doses 4 weeks apart. After initial cold storage it can be kept between 2°C and 8°C for up to 8 weeks.
Although it is not currently licensed for persons under 18 years of age, the vaccine can be used “off-label” in infants, children, and adolescents, and in pregnant and immunocompromised people. This allows use in an outbreak after consideration of the potential risks in relation to the benefits of vaccination.
Data available to WHO reveal that a single-dose MVA-BN vaccine, administered before exposure, has an estimated 76% effectiveness in protecting against mpox; the two-dose schedule achieves an estimated 82% effectiveness. Post-exposure vaccination is less effective. Clinical studies have demonstrated a good safety profile and vaccine performance, which have been confirmed in real-world use during the global outbreak since 2022. However, WHO emphasises the need to collect “as much data as possible on vaccine safety and effectiveness in different contexts”.
An important step
Dr Tedros Adhanom Ghebreyesus, WHO Director-General, described this first prequalification as an “important step in our fight against the disease” with implications for current outbreaks and the future.
“We now need urgent scale up in procurement, donations, and rollout to ensure equitable access to vaccines where they are needed most, alongside other public health tools, to prevent infections, stop transmission, and save lives.”
WHO Assistant Director-General for Access to Medicines and Health Products, Dr Yukiko Nakatani, suggested that the prequalification will “help accelerate ongoing procurement” to help communities “on the frontlines of the ongoing emergency in Africa and beyond”.
“The decision can also help national regulatory authorities to fast-track approvals, ultimately increasing access to quality-assured mpox vaccine products.”
Dr Rogerio Gaspar, WHO Director for Regulation and Prequalification, commented that the findings of the product and programmatic suitability assessments are “particularly relevant in the context of the declaration of a public health emergency of international concern (PHEIC)”.
“We are progressing with prequalification and emergency use listing procedures with manufacturers of two other mpox vaccines: LC-16 and ACAM2000. We have also received 6 expressions of interest for mpox diagnostic products for emergency use listing so far.”
To explore the steps before, during, and after these approval processes in emergency contexts, join us at the Congress in Barcelona this October. Don’t forget to subscribe to our weekly newsletters here for regular updates.
by Charlotte Kilpatrick | Sep 10, 2024 | Technology |
A paper from Vaccines Europe in September 2024 reveals “key vulnerabilities” in the vaccine supply chain and offers strategies to strengthen resilience. The paper addresses the “main causes” of vulnerabilities, how manufacturers are addressing the issues disrupting resilience, and how regulators and policymakers can “enhance” these measures to ensure resilience.
“The underlying principle of vaccine supply chain resilience is that the design of supply chain systems should ensure their capacity to recover critical functions when significant disruptions occur. This resilience is based on robust and agile global supply chains.”
Disruptions can include conflict, health threats, or “catastrophes caused by climate change”, and addressing these events demands a “thorough understanding of key vulnerabilities” in the supply chain and the ability to “respond with flexibility and agility”.
Vaccine vulnerabilities
The authors acknowledge the various stages of vaccine development and delivery from manufacturing and testing to regulatory requirements. Vaccines are “often highly technical, complex biological products”. Although the COVID-19 vaccines had a shorter production lead time, the general production lead time is over a year. Additionally, the “complexities and strict requirements of daily performance” affect the vaccine supply chain.
The time required for designing, building, validating, securing regulatory approvals, and starting commercial manufacturing and distribution of a vaccine ranges between 5 and 10 years. Specific manufacturing processes and facilities hinder the expansion of manufacturing capacity when demand increases.
Another limiting factor is the need for different languages on vaccine packs and leaflets; multi-lingual packs are “limited to a maximum of three languages”. This means that “at least 14” different packs are needed for a single presentation of a centrally approved vaccine for coverage across all EU/EEA countries. Manufacturers must “cluster production”.
The COVID-19 pandemic highlighted that “lack of transparency” at any stage in the supply chain can increase the risk of supply shortages. The combination of “unpredictable” demand and a lack of dialogue between manufacturers and health authorities contribute to supply shortages. While some countries conduct “horizon scanning”, other countries do not have these mechanisms in place.
Other factors contribute to supply shortages:
- Environmental factors
- Geopolitical factors
- Economic factors
- Technological factors
- Regulatory factors
- Tender practices
Addressing issues: manufacturers
“Manufacturers are committed to maintaining the supply of vaccines to the community and are therefore implementing a series of measures to reduce potential supply disruptions, where possible and appropriate.”
To deal with threats, vaccine manufacturers have “multiple mitigation plans”:
- Quality systems – good manufacturing practices, staff training, employing qualified personnel, validation of new equipment and facilities
- Proactive risk management (multi-sourcing) – multiple sources for raw materials
- Supply continuity plans – strategies to ensure product delivery is maintained during disruptions
- Fit-for-purpose shortage prevention plans – a risk management process focusing on manufacturing capabilities, sourcing of raw materials, market trends, marketing activities, and product supply
- Updated business contingency plans – plans to resume normal business operations after unintended interruptions like natural disasters, data loss, or demand shifts.
- Diversity of geographical locations of key suppliers – prevents reliance on supplies from the same country/region if disruptions occur
- Inventory management – systems designed to monitor stock levels and order demands
Addressing issues: regulators and policymakers
“Regulators and policymakers can help enable strategies already being employed by vaccine manufacturers and ensure any future policy solutions are proportionate to the risk, carefully considering unintended effects and backed by strong evidence on the nature of shortages.”
Strategies to achieve this include:
- Improving demand forecast transparency: manufacturers must be able to access information on needs and employ a coordinated mechanism for vaccine allocation. The EU and Member States should ensure regulatory expertise and resources and enhance transparency in the decision-making process regarding vaccine assessment. Constant communication with suppliers ensures transparency and successful planning on policy and programme implementation. Data sharing also allows understanding of demand.
- Implement successful strategies from the COVID-19 pandemic during non-pandemic times: policies should support manufacturing capacities, free trade of raw materials and vaccines, and the freedom to select suppliers. Removing export restrictions, opening borders, and ensuring diversified supply chains are “key”. Supply chains can also be strengthened with improved distribution channels to “alleviate bottlenecks”. During the pandemic, “official green lanes (or corridors)” were established to facilitate customs clearance at border crossings. Additional “dialogue on open supply chains with like-minded countries” are “critical in driving sustainable and globally aligned approaches”. Harmonised regulatory standards also provide “system-wide benefits”; the pandemic showed that rolling submissions, potential for electronic or hybrid inspections, conditional marketing authorisations, and acceptance of the EU common pack and electronic Patient Information Leaflet accelerated access. Here, again, information and data sharing are “essential for improved understanding of vaccine demand forecast”.
- Encouraging stakeholder collaboration to create synergies for strengthened resilience: “essential synergies” ensure understanding of the vaccine production process, avoid delays and duplication of work, and shape future activities. Stakeholders must be effectively engaged, and “diverse modes of collaboration” will allow vaccine development within tight timeframes. Communication between national, EU, international health agencies, authorities, and manufacturers is “critical”. Key partnerships during the COVID-19 pandemic “bolstered manufacturing capacity”, enabled technology and knowledge transfer, accelerated research and development, and encouraged “unprecedented” manufacturing scale-up.
- Reducing packaging complexities: the authors encourage the adoption of a common EU packaging accepted by Member States and replacing the paper patient information leaflet with an electronic version (ePIL). Regulatory flexibilities would allow redeployment of inventory between countries.
- Ensuring a highly skilled vaccine manufacturing and supply chain workforce: policy priorities include “upskilling” the EU vaccine workforce and providing support to Member States for improved research, development, and manufacturing capabilities; varied infrastructure and workforce capabilities demand investment.
Collaboration
“Addressing these root causes is largely beyond the control of manufacturers alone and will require mutually feasible and sustainable solutions in collaboration between competent authorities, governments, and industry.”
Vaccines Europe concludes that a complete understand of the end-to-end vaccine production and batch release processes is critical to preventing delays. Optimising collaboration, minimising duplicate efforts, and increasing resilience and agility for the future will “ultimately improve vaccine availability and contribute to better public health”.
We look forward to welcoming Vaccines Europe to the Congress in Barcelona this October for sessions on vaccine development and policy. Get your tickets to join us there, and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Sep 6, 2024 | Technology |
A paper in Cell in September 2024 presents a promising mRNA vaccine candidate against mpox disease. The mRNA-lipid nanoparticle (LNP) vaccine expresses MPXV surface proteins and was compared with modified vaccinia Ankara (MVA) vaccine, proving to confer protection against challenge and mitigate symptoms and disease duration. Furthermore, it provided “enhanced viral control and disease attenuation” compared to MVA, which highlights the potential of mRNA vaccines against future pandemic threats.
A new modality
Despite the availability of an effective vaccine against mpox, the authors note “issues in supply, unfavourable reactogenicity, incomplete immunity, and uncertainty of cross-protection”. These factors provide “critical motivation” for the pursuit of a new vaccine modality for “improved vaccines to cover these gaps”. mRNA vaccines offer “unprecedented flexibility, speed, and immunogenicity”. However, it was unclear whether an mRNA vaccine could provide “comparable immune protection” to a whole attenuated poxviral vaccine vector.
The study
The authors used a stringent clade I MPXV Zaire 1979 (Z79) MPXV nonhuman primate (NHP) model to assess the protective efficacy of mRNA-1769, an mRNA-lipid nanoparticle (LNP) vaccine. It expresses optimised versions of four antigens of interest (A29, A35, B6, and M1). This vaccine was compared with mRNA; both vaccines were administered in “clinically relevant doses”.
Both vaccines conferred “complete protection” after lethal MPXV challenge. However, mRNA-immunised animals experienced 10-fold fewer lesions, reduced disease duration, and “substantial” mitigation of circulating and mucosal viraemia. Furthermore, deep immunological profiling of the humoral response revealed more robust MPXV neutralising responses, broadly reactive heterologous neutralising titres, and greater functional humoral immune responses against the four antigens in the mRNA-immunised animals.
Immune correlates analyses highlighted the “critical coordination” between neutralising and Fc-effector functions against both EV and MV targets, EV-Fc target-specific functions and neutralisation as key correlates of antiviral control, and EV target-antigen-specific opsonophagocytic activity and neutrophil/natural killer cell-targeted functions to the MV as “key determinants” of lesional control. These results suggest that the mRNA-LNP vaccine induced a robust functional humoral response that provided protection against a lethal MPXV challenge. This is like MVA immunisation but with the benefit of “superior protection against disease”.
“These data provide critical insights into mRNA-vaccine-induced correlates of immunity against MPXV, which can support licensure, provide mechanistic insights on vaccine performance, support optimised vaccine usage in vulnerable populations, and inspire redesign should novel Orthopoxviral threats emerge requiring antigen addition or alteration.”
Rapid responses
The authors reflect on the “lack of vaccine deployment and access to medical countermeasures”, which has “fuelled the spread” of mpox from “traditionally endemic rural areas” to larger metropolitan centres. They suggest that lack of routine immunisation with contemporary VACV-based vaccines has provided “fertile ground” for low-level spread of the virus and opportunities for mutation.
“Thus, additional safe and highly efficacious vaccine platforms that are rapidly adaptable upon viral mutation are urgently needed.”
Nucleic-acid vaccines, like mRNA-LNP vaccine technologies, facilitate rapid responses to emerging viral threats. Sequences against key genes can be synthesised and converted into a potential vaccine quickly, and production can take place at regions of interest through worldwide manufacturing centres.
Join us at the Congress in Barcelona to participate in discussions about the potential of mRNA vaccines against various diseases and don’t forget to subscribe to our weekly newsletters for regular vaccine updates.
by Charlotte Kilpatrick | Sep 4, 2024 | Technology |
3PBIOVIAN announced in September 2024 that it has been selected by Rokote Laboratories Finland Ltd. as CDMO partner for GMP manufacturing of adenovirus type 5 (Ad5) vector-based candidate expressing a modified SARS-CoV-2 spike protein. The partnership aims to bring Rokote Laboratories’ intranasal FINCoVac 2.1 vaccine to Phase I clinical studies with 3PBIOVIAN providing Drug Substance and Drug Product. FINCoVac 2.1 is intended to elicit a strong mucosal immune response in the nasopharyngeal cells, potentially preventing infection and transmission.
Ad5 vector
The agreement covers GMP manufacturing of the Ad5 vector using 3PBIOVIAN’s standard process at facilities in Turku, Finland. With “extensive experience” in adenovirus GMP manufacturing solutions, 3PBIOVIAN pursues “successful scalability and GMP compliance”. To meet Rokote Laboratories’ “urgent” needs, the programme has advanced “exceptionally fast”.
FINCoVac 2.1
Rokote Laboratories seeks to “consolidate” the use of new vaccine technology in Finland, focusing on a second-generation coronavirus vaccine, FINCoVac 2.1. It is designed to “meet the challenge of the rapidly mutating variants” with applications as an “easy-to-dose booster”. The vaccine consists of an adenoviral vector, to which the SARS-CoV-2 viral spike protein gene has been transferred. FINCoVac is administered intranasally, so it is expected to offer a “wider immune response” than vaccines that are administered intramuscularly.
Dr Erkko Ylösmäki, CEO of Rokote Laboratories, is pleased with the partnership with 3PBIOVIAN to manufacture the vaccine.
“The ability to use 3PBIOVIAN’s standard process for rapid GMP batch production, along with their extensive experience with adenovirus-based processes, made 3PBIOVIAN the ideal CDMO partner.”
Dr Ylösmäki is excited to start the collaboration and hopes that “together we can further advance Finnish vaccine development”. Deputy CEO at 3PBIOVIAN, Antti Nieminen, commented that the company has “about two-decade-long history” in viral vector development processes and GMP-manufacturing of adenoviruses.
“We are happy to have a role in the journey of this novel second-generation coronavirus vaccine to clinical trials.”
For the latest vaccine manufacturing insights and updates at the Congress in Barcelona this October, get your tickets here, and make sure you’ve subscribed to get our weekly newsletters.
by Charlotte Kilpatrick | Sep 3, 2024 | Technology |
Vaxcyte announced in September 2024 that its Phase I/II study of VAX-31, the 31-valent pneumococcal conjugate vaccine (PCV), has produced positive topline results. The study evaluates the safety, tolerability, and immunogenicity of the vaccine in healthy adults aged 50 and older. With strong results from the study, the company will take VAX-31 forward to an adult Phase III programme.
VAX-31 in trial
VAX-31 is Vaxcyte’s 31-valent PCV candidate for the prevention of invasive pneumococcal disease (IPD). IPD is “especially serious” in infants, young children, older adults, and people with immune deficiencies or some chronic health conditions. The vaccine candidate is the “broadest-spectrum PCV in the clinic” and offers the potential to protect against serotypes in circulation and historically prevalent serotypes.
The Phase I/II study was a randomised, observer-blind, active-controlled, dose-finding clinical study to evaluate the safety, tolerability, and immunogenicity of a single injection of VAX-31 at three dose levels and compared to PCV20 in 1,015 healthy adults aged 50 and older.
Making progress
The following results were released:
- Full six-month safety data show that VAX-31 was well tolerated and demonstrated a similar safety profile to PCV20 at all doses studied.
- Frequently reported local and systemic reactions were “generally mild-to-moderate” and no serious adverse events were linked to study vaccines.
- The vaccine candidate showed “robust” opsonophagocytic activity (OPA) immune responses for all 31 serotypes at all doses studied.
- At high and middle doses, VAX-31 met or exceeded regulatory immunogenicity criteria for all 31 serotypes. At the low dose it met or exceeded regulatory immunogenicity criteria for 29 of the 31 serotypes.
- For the 20 serotypes shared with PCV20:
- At high dose all 20 met the OPA response non-inferiority criteria, 18 out of 20 had a geometric mean ratio (GMR) greater than 1.0, and seven serotypes achieved statistically higher immune responses.
- At middle dose all 20 met the OPA response non-inferiority criteria, 13 of 20 had a GMR greater than 1.0, and five serotypes achieved statistically higher immune responses.
- At low dose, 18 of 20 met the OPA response non-inferiority criteria, 8 of 20 had a GMR greater than 1.0, and three serotypes achieved statistically higher immune responses.
- For the 11 serotypes exclusive to VAX-31 all three doses met superiority criteria.
Potential as best-in-class
CEO and Co-Founder of Vaxcyte, Grant Pickering, believes the positive results “affirm the potential” of the “site-specific, carrier-sparing platform to deliver the broadest-spectrum PCVs”.
“Based on the strength and clarity of these data, we have selected VAX-31 for the adult indication and plan to initiate the pivotal, non-inferiority Phase III study by mid-2025 and announce topline data in 2026.”
Mr Pickering shared that the company intends to initiate the remaining VAX-31 Phase III studies in 2025 and 2026 and submit a Biologics License Application (BLA) “subject to the results of these studies”. Vaxcyte’s Executive Vice President and Chief Operating Officer Jim Wassil is “exceptionally proud to share these results”, which “validate VAX-31’s potential as a best-in-class pneumococcal vaccine”. VAX-31 is capable of “raising the bar for immunogenicity standards”.
“The public health community continues to highlight the need for broader-protection vaccines to prevent IPD, which is associated with high case-fatality rates, antibiotic resistance, and meningitis. To address this need, VAX-31 was designed to increase coverage to more than 95% of IPD circulating in adults 50 and older in the US.”
Mr Wassil suggested that VAX-31 has “potential to provide significantly greater coverage relative to today’s standard-of-care adult PCVs”. He extended “sincere gratitude to everyone involved in the programme”, particularly participants, trial investigators and sites, and the team at Vaxcyte.
To hear the latest vaccine development updates at the Congress in Barcelona this October get your tickets to join us here, and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Sep 3, 2024 | Technology |
In September 2024, Valneva and Pfizer announced positive immunogenicity and safety data from the VLA15-221 Phase II study investigating a second booster vaccination of their Lyme disease vaccine candidate. The vaccine, VLA15, is administered one year after receipt of the first booster dose. The immune response and safety profile one month after the VLA15 booster dose were similar to those reported after the first booster dose, which shows “compatibility with the anticipated benefit” of a booster vaccination before each Lyme season.
VLA15
VLA15 is the most advanced Lyme disease vaccine candidate; there are no approved human vaccines for the disease. It is an investigational multivalent protein subunit vaccine that uses an established mechanism of action for a Lyme disease vaccine to target the outer surface protein A (OspA) of Borrelia burgdorferi, the Lyme disease-causing bacteria. OspA is expressed by the bacteria when present in a tick, so blocking it inhibits the bacterium’s ability to leave the tick and cause infection in humans.
The vaccine targets the six most prevalent OspA serotypes expressed by the Borrelia burgdorferi sensu lato species in North America and Europe. It is tested as an alum-adjuvanted formulation and administered intramuscularly.
Phase II study
VLA15-221 is a randomised, observer-blind, placebo-controlled Phase II study, the first clinical study of VLA15 to enrol a paediatric population (5-17 years). 560 healthy participants received either VLA15 in two immunisation schedules or placebo. The study is being conducted at US sites in areas where Lyme disease is endemic.
The most recent results “demonstrated a significant anamnestic antibody response” for all six serotypes in paediatric, adolescent, and adult participants. This was measured one month after administration of the second booster. Many participants seroconverted after the second booster dose, yielding seroconversion rates (SCRs) above 90% for all OspA serotypes in all age groups. Geometric Mean Titres were “comparably high” at one month post first and second booster.
Encouraging data
Dr Juan Carlos Jaramillo, Valneva’s Chief Medical Officer, is “encouraged” by the data, which “support the potential benefit of booster doses across all examined age groups”.
“As Lyme disease continues to spread, it represents a significant unmet medical need, affecting numerous individuals throughout the Northen Hemisphere. Each new set of positive data brings us one step closer to potentially bringing this vaccine to both adults and children living in areas where Lyme disease is endemic.”
Dr Annaliesa Anderson, Senior Vice President and Head of Vaccine Research and Development at Pfizer, reflected that the “only recommended strategies” for protection against Lyme disease are “personal preventive behaviours”.
“These data from the VLA15-221 study are an important step towards a potential vaccine that could help prevent the disease and ease the burden of acute, severe, and sometimes persistent consequences. Together with our partner Valneva, we look forward to progressing our vaccine candidate in the ongoing Phase III clinical trials.”
The ongoing Phase III clinical study, Vaccine Against Lyme for Outdoor Recreationists (VALOR) was initiated in August 2022 to investigate the efficacy, safety, and immunogenicity of VLA15 in participants aged 5 years and older in highly endemic regions in the US and Europe. There is also a second ongoing Phase III study (VLA15-1012) to provide further evidence on the safety profile of VLA15 in the paediatric population. Pfizer intends to submit a Biologics License Application (BLA) to the US FDA and Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) in 2026, subject to positive Phase III data.
For vaccine development insights at the Congress in Barcelona, get your tickets to join us here, and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Aug 30, 2024 | Technology |
In August 2024, Emergent BioSolutions announced that the US FDA has approved the supplemental Biologics License Application (sBLA) for the expansion of the indication for ACAM2000 to include prevention of mpox disease in individuals determined to be at high risk for mpox infection. The approval draws on previous human safety data and animal data, where ACAM2000 was shown to be effective in protecting against mpox virus exposure. ACAM2000 is a single-dose vaccine administered percutaneously through a bifurcated needle.
ACAM2000
ACAM2000 is the primary smallpox vaccine designated for use in a bioterrorism emergency; it is indicated in the US for active immunisation for the prevention of smallpox and mpox disease in individuals determined to be at high risk for smallpox and mpox infection. It was first approved by the FDA in 2007 for active immunisation for the prevention of smallpox disease in individuals determined to be at high risk for smallpox infection. The FDA approval follows the announcement that Emergent has filed an Expression of Interest (EOI) with WHO for consideration for Emergency Use Listing.
Emergent’s president and CEO Joe Papa commented that the FDA approval “further strengthens and broadens” Emergent’s “industry-leading smallpox portfolio”.
“This expanded indication for ACAM2000 comes at a critical time as the global health community comes together to ensure an effective and cohesive response to the recent upsurge in mpox cases. We believe Emergent is poised to support the global response needed by actively engaging with world health leaders, as well as deploying product currently available in inventory based on the needs, as well as the ability to increase supply.”
Dr Amesh A. Adalja, FIDSA FACP FACEP, health security and emerging infectious diseases expert, Johns Hopkins Centre for Health Security, described the “enormous need to use all effective tools to extinguish” the “uncontrolled epidemic” of mpox.
“ACAM2000, a direct descendent of the Jenner vaccine (humanity’s first) which was used to eradicate smallpox, and now with the broadened indication, will be an invaluable tool in this endeavour.”
For more on the vaccine community’s efforts to address the growing threat of mpox, join us at the Congress in Barcelona this October. Don’t forget to subscribe to our weekly newsletters for vaccine updates here.
by Charlotte Kilpatrick | Aug 29, 2024 | Technology |
Researchers from the University of Oxford shared their work in npj vaccines in August 2024, addressing the threat of “substandard and falsified vaccines” through a matrix-assisted laser desorption/ionisation-mass spectrometry (MALDI-MS) workflow. Their study validates this method, showing that multivariate data modelling and diagnostic mass spectra can be used to identify authentic or falsified vaccines. The team is “thrilled” that their work has potential for real-world vaccine authenticity screening.
The threat of SF medicines
The authors state that an increase in substandard or falsified (SF) medicines “threatens public health on a global scale”. Indeed, WHO has identified SF medicines as an urgent health challenge for the coming decade. SF vaccine products have become more prolific, including rabies, cholera, and COVID-19 vaccines. In the first 15 months of the global COVID-19 vaccination programme there were “over 184 reports” of diverted and SF COVID-19 vaccines, involving “millions of doses”.
“A range of adulteration and falsification incidents have been identified, including replacement of vaccines with saline or other adjuvants such as sugar solutions and antibiotics, and errors in manufacture have led to substandard production.”
Substandard vaccines come from “inadvertent” manufacturing errors and/or supply chain degradation. By contrast, falsified vaccines arise from “criminal, fraudulent activities”. Although the “origins and solutions” to these are different, both are a “major health risk” with the potential to cause increased morbidity and mortality and “undermine the reputation of vaccines as safe medical products”.
“With a rise in vaccine use globally, it is becoming increasingly clear that a lack of risk analysis, monitoring, and intervention within supply chains is allowing the problem of vaccine falsification, in particular, to develop.”
The paper highlights a “significant vulnerability” in the lack of testing and monitoring, and the authors demand new methods for “risk-based post-market surveillance”. However, they recognise the need for a range of techniques, devices, and methods to effectively monitor supply chains, which are “complex”. Furthermore, many countries are not equipped to check the quality of different vaccines, so testing methods are needed in central facilities to “rapidly give detailed information to facilitate decisions”.
MALDI-MS and vaccine applications
To address the “growing need” for vaccine authenticity testing and “current lack of suitable methods”, the researchers explored matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS). Mass spectrometry is an “important platform for molecular-level profiling” with high sensitivity and selectivity. Machine learning and statistical approaches can also be used to classify samples and identify biomarkers. MALDI-MS has “low sample volume requirements” and the analysis has a “high-throughput nature”, offering “significant benefits”.
“The heterogeneity of different vaccines, both in terms of diversity in active constituents, physiochemical properties and concentrations, makes samples challenging to characterise from an analytical perspective.”
The “inherent sensitivity and molecular selectivity” of MALDI-MS, combined with existing worldwide availability of instrumentation, encouraged the authors to explore its potential as a vaccine authentication device. They focused on the capabilities of MALDI-MS “biotyping” systems for vaccine analysis by developing a method and validating it for the analysis of authentic vaccine samples, falsified vaccines, and their categorisation with machine learning approaches.
The study
The researchers used four different authentic, commercially available vaccines: Nimenrix, Engerix B, Flucelvax Tetra, and Ixiaro. They also used eight falsified surrogates previously reported in falsified vaccine products. Two different MALDI systems were chosen; these are distributed globally, which provides potential as a resource for global supply chain monitoring. The two instruments produced “very similar performance” in combination with data modelling, but “slightly different” mass spectral profiles when visually compared.
After establishing proof-of-principle that the MALDI-MS systems could measure mass spectral peaks to distinguish genuine comparator vaccines from falsified vaccine surrogates, the team developed and validated a method and workflow for data processing and analysis. This was applied to analyse and compare authentic and falsified vaccine constituents using both platforms in parallel.
To overcome potential variability in mass spectral peak intensities, the authors tested analytical, experimental, and vaccine vial reproducibility to reveal that post-acquisition data processing was “effective” against these effects. Partial least squares-discriminant analysis (PLS-DA) demonstrated that a machine learning approach can model MALDI-mass spectral peaks and their intensities for discriminating authentic and falsified vaccines.
“This research demonstrates that a MALDI-MS method has the potential to be deployed in an international supply chain setting given that the instrumentation used is currently globally distributed for healthcare applications.”
Next, the authors recommend developing and testing a “comprehensive online database” for automated vaccine testing. Furthermore, they suggest the possibility of evaluating the utility of MALDI-MS to detect a wider range of substandard vaccines. Professor James McCullagh, study co-lead and Professor of Biological Chemistry in the Department of Chemistry is “thrilled” to see the method’s effectiveness and potential for “deployment into real-world vaccine authenticity screening”.
“This is an important milestone for The Vaccine Identity Evaluation (VIE) consortium, which focuses on the development and evaluation of innovative devices for detecting falsified and substandard vaccines, supported by multiple research partners.”
Co-author Professor Nicole Zitzmann of the Department of Biochemistry hopes the research will “bring the world community one step closer” to differentiating between falsified vaccines and the “real thing”.
“It has been a tremendous collaborative effort, with everyone having this same important goal in mind.”
Co-author Professor Paul Newton of the Centre for Tropical Medicine and Global Health is also pleased with the results.
“This innovative research provides compelling evidence that MALDI mass spectrometry techniques could be used in accessible systems for screening vaccine falsification globally, especially in centres with hospital microbiology laboratories, enhancing public health and confidence in vaccines.”
For more on efforts to ensure vaccine safety and quality at every stage of development and deployment, why not join us at the Congress in Barcelona this October? Get your tickets now and don’t forget to subscribe for weekly vaccine updates.
by Charlotte Kilpatrick | Aug 28, 2024 | Technology |
Bharat Biotech announced the launch of HILLCHOL in August 2024, describing the novel single-strain oral cholera vaccine (OCV) as a “significant advancement in global health”. With only one manufacturer supplying OCVs globally, there is a yearly deficit of ~40 million doses. Thus, Bharat Biotech has established manufacturing facilities in Hyderabad and Bhubaneswar with the capacity to produce “up to 200 million doses” of the vaccine. HILLCHOL is administered orally on Day 0 and Day 14 to individuals older than one year.
HILLCHOL
Hilleman Laboratories compares HILLCHOL with existing cholera vaccines, which contain more than one strain; HILLCHOL uses a single, genetically engineered, inactivated ‘Hikojima’ strain, which reduces production costs and will expand access amid increasing outbreaks. HILLCHOL is presented in a mono-multidose format and should be stored at temperatures between 2°C and 8°C. It is intended to contribute “substantially” to the Global Task Force on Cholera Control (GTCC) effort of reducing cholera-related deaths by 90% for 2030. The vaccine is the result of “extensive” international collaboration.
Dr Krishna Ella, Executive Chair of Bharat Biotech, states that it is an “excellent success story of partnership leading to public health solutions”.
“Vaccines provide the best intervention to prevent, limit, and control cholera outbreaks.”
With new large-scale cGMP production facilities, Dr Ella is confident that Bharat Biotech’s production and supply capabilities are “significantly” enhanced. Hilleman Laboratories’ CEO, Dr Raman Rao, commented that “from day one our mission has been to develop affordable vaccines and biologics” for “countries with the most severe unmet medical needs”.
“This new vaccine delivers on that pledge and provides an innovative template for the internationalisation of future vaccine and biologics development from Singapore, that can positively impact global health.”
Dr Rao highlighted the pride that Hilleman Laboratories takes in the “joint effort” and ongoing “dedication to advancing global health equity through affordable, high-impact, and sustainable solutions for those who are most susceptible”.
For more on powerful vaccine partnerships driving global health innovation, get your tickets to the Congress in Barcelona this October, and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Aug 27, 2024 | Technology |
Immorna Biotherapeutics announced in August 2024 that it has received a grant, worth $3,800,000, from the Bill & Melinda Gates Foundation in support of the clinical development of JCXH-108. JCXH-108 is a Respiratory Syncytial Virus (RSV) vaccine based on Immorna’s proprietary mRNA and ‘ready-to-use’ lipid nanoparticle (RTU-LNP) technologies. The grant will provide staged financial support to expedite clinical trials in the US, the process and clinical development of multi-dose vial vaccine (MDV), a marketing application in the US, and WHO Pre-Qualification (PQ). If the vaccine is approved for marketing, Immorna has committed to supplying it to LMICs at a pre-negotiated price.
JCXH-108
JCXH-108 is a monovalent RSV vaccine that uses Immorna’s mRNA and RTU-LNP technologies, which have “gained successful clinical proof-of-concept” in other infectious disease vaccines. This vaccine encodes an engineered RSV Fusion protein with stabilised pre-fusion configuration (pre-F). The pre-F antigen demonstrated “high” in vitro and in vivo expression from the mRNA in preclinical studies, and low doses of JCXH-108 elicited high titres of neutralising antibodies against both RSV A and RSV B strains.
The vaccine “features a mild storage and transportation condition” with a shelf life of around 18 months at between 2°C and 8°C. Enhanced stability should “significantly reduce the logistics complexity” associated with mRNA vaccine storage, transportation, and distribution.
Reducing the burden of RSV
Dr Zihao Wang, Co-Founder and CEO of Immorna, appreciates the “trust and support” shown by the foundation as the company strives to introduce a “safe and effective” RSV vaccine to reduce RSV related hospitalisations and deaths.
“We look forward to working closely with the foundation to expedite the clinical development and marketing of JCXH-108. As a biotech company developing mRNA-based vaccines and therapeutic drugs, Immorna closely follows the global needs for prevention of infectious diseases and strives to help provide more treatment options to patients.”
Dr Wang emphasises the focus on contributing to the creation of a “disease-free, better future”.
“I believe that, if successfully approved for marketing, JCXH-108 may help protect millions of susceptible individuals and their families from the deadly diseases associated with RSV infection, which is particularly meaningful in the LMICs where RSV infection is prevalent.”
Immorna is “on track” to enrol the first subject in a clinical trial by the end of August 2024.
To hear from experts on different approaches to RSV prevention and mitigation, why not get your tickets to join us in Barcelona for the Congress this October? Don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Aug 27, 2024 | Technology |
Tonix Pharmaceuticals announced in August 2024 that it is collaborating with Bilthoven Biologics (BBio) to advance TNX-801. TNX-801 is Tonix’s mpox vaccine candidate, a live replicating, attenuated virus vaccine based on horsepox. It has demonstrated better tolerability than 20th century vaccinia viruses in animal models, and preclinical studies have shown “positive” efficacy data.
TNX-801
Tonix’s TNX-801 is in preclinical development for the prevention of mpox and smallpox. In preclinical studies, Tonix found that TNX-801 vaccination protected non-human primates against lethal challenge, prevented clinical disease and lesions, and decreased shedding in the mouth and lungs. It is delivered percutaneously as a single dose, which could enable “higher rates of community protection”.
“TNX-801 has the potential to make a global impact on mpox and the risk of smallpox because of its durable T-cell immune response, the potential to manufacture at scale, and the use of a lower dose than non-replicating vaccines.”
Bolstering preparedness and response
Jurgen Kwik, Chief Executive Officer at Bilthoven Biologicals, believes that the current mpox outbreak “exemplifies precisely why we built the pandemic preparedness facility at BBio”.
“The establishment of the ‘ever-warm’ facility for pandemic preparedness underscores the critical importance of readiness in the face of global health emergencies, such as mpox. This collaboration encapsulates the essential role of the facility in bolstering pandemic preparedness and response capabilities.”
Dr Seth Lederman, Chief Executive Officer of Tonix Pharmaceuticals, looks forward to collaborating with BBio and “accelerating the development of our vaccine candidate to prevent mpox”. Dr Lederman believes that the single dose administration will “improve acceptance and eliminate partial vaccination” when compared to the current two-dose regimens.
“We believe TNX-801 can be rapidly scaled up for manufacturing and can be distributed and stored without a costly and cumbersome ultra-cold supply chain.”
Dr Lederman highlighted that the “worldwide availability of an affordable, safe, and effective single dose” vaccine against mpox is “essential given the pandemic potential of the disease”. Furthermore, successful development of TNX-801 would “establish the foundation” for potential expansion of the viral vector platform.
We look forward to learning more about this vaccine at the Congress in Barcelona this October; get your tickets to join us there and don’t forget to subscribe for more vaccine updates here.
by Charlotte Kilpatrick | Aug 27, 2024 | Technology |
CEPI announced in August 2024 that it is providing US$2.05 million to researchers at Afrigen Biologics to support their work on synthetic DNA. The scientists are exploring if it can act as an alternative to the “traditional” plasmid DNA required for mRNA vaccines, thus accelerating the initial phase of vaccine development. The partnership supports CEPI’s 100 Days Mission by seeking to make vaccine development “up to three time faster”.
Optimised synthetic DNA
Plasmid DNA (pDNA) is traditionally used in mRNA vaccines as the “start material” containing genetic instructions to produce a specific viral protein. pDNA is produced through bacterial fermentation, which can take over 30 days.
“This process is time-consuming and expensive, and timelines can be further compounded by insufficient manufacturing capacity and supply chain issues.”
A potential alternative is optimised synthetic DNA (oDNA), manufactured by Syngoi. It is produced by enzymes in a cell-free process that demands a smaller manufacturing footprint, can be rapidly produced in just 10 days, and is less costly. The proof-of concept project between CEPI and Afrigen will explore this technology by using pDNA and oDNA to develop and mRNA vaccine for Rift Valley Fever.
“If successful, the oDNA technology could accelerate the production of clinical trial material required to test new mRNA vaccines in human clinical trials and ultimately make vaccines available more swiftly to those most in need.”
Prioritising equity
Ingrid Kromann, Acting Executive Director, Manufacturing and Supply Chain, CEPI, commented that mRNA vaccine manufacturing processes are “fast and flexible”.
“Innovative technologies like optimised synthetic DNA can make them even faster. CEPI’s partnership with Afrigen could reduce the vaccine development timelines by addressing the challenges associated with plasmid-DNA supply, helping get vaccines to people faster in the face of an outbreak and reduce inequity.”
As the WHO/Medicines Patent Pool Hub for mRNA Technology Transfer Programme, Afrigen acts as a centre of excellence and training for the initiative, seeking to build mRNA vaccine production capacity in low- and middle-income countries. This new partnership could enable local manufacturing of vaccines in Africa, supporting CEPI’s strategy to “geo-diversify” global manufacturing capabilities. Professor Petro Terblanche, Afrigen CEO, described the partnership as a “strategic milestone” that demonstrates the “important contribution that biotechnology start-up companies can make to innovation”.
“We are enthusiastic about the contribution this joint project can make to the speed and cost of mRNA vaccine manufacturing.”
We look forward to hearing more on regional capacity for equitable vaccine distribution from Professor Terblanche at the Congress in Barcelona this October; get your tickets to join us here and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Aug 22, 2024 | Technology |
The Pandemic Institute announced in August 2024 that it has signed a Memorandum of Understanding (MoU) with Pharma Latch after attending the Congress in Washington this April. The collaboration will pursue several projects focused on optimising technology for safe, effective, and acceptable vaccines. Pharma Latch’s “unique” technology allows simple and efficient intradermal vaccine delivery and a “near pain free solution”. This has been identified by The Pandemic Institute as a promising avenue to encourage vaccine uptake.
Pharma Latch devices
Pharma Latch states that intradermal delivery can “enhance the efficacy” of various vaccine platforms. The technology “eliminates” user-dependency and variability associated with traditional intradermal injection techniques. The “Latch” platform uses opposing arrays of hypodermic needles of fixed length and angles. They work in pairs when deployed to establish a “slight stretching” of the skin, enabling full penetration of the needles to a predetermined depth.
Benefits include:
- Improved immune response
- Dose sparing
- Improved patient compliance and experience
- Complete dose delivery
- Simple to use devices
- High payload capability
- Low-cost, highly scalable device
Prevent and respond
The Pandemic Institute has five major research themes: Predict, Prepare, Prevent, Respond, and Recover. Central to these efforts is the development of new vaccines and community engagement to understand how to increase their acceptability. Some of the projects the collaboration will progress include:
- Patient acceptability of intradermal injection technology
- Assess the immune response when using the new technology in pre-clinical trials
- Assess how the technology works in delivering vaccines in a clinical trial
Professor Cathy Montgomery, Professor of Psychopharmacology and Health Inequalities at Liverpool John Moores University is “excited to be working with Pharma Latch to explore this new device” and uncovering the “benefits it could bring” to increasing uptake.
“Vaccine hesitancy is a rising concern in controlling infectious diseases, and anxiety around perceived pain and blood injection injury phobia (needle phobia) can be strong factors to hesitancy.”
Professor Tom Solomon CBE, University of Liverpool’s Infection, Veterinary, and Ecological Sciences Institute and Director of The Pandemic Institute is also “excited to be working with Pharma Latch going forward”.
“This new collaboration showcases what The Pandemic Institute does best – bringing together key people from across our partnership with external partners to ensure that we are putting things in place now for when the next pandemic emerges.”
Pharma Latch’s CEO, Ronan Byrne, is “delighted” with the partnership.
“We are impressed with both the breadth of ability and resources available and excited about the planned projects we will be looking to progress together.”
VaccineNation is thrilled to see the Washington Congress mentioned by The Pandemic Institute, particularly as Pharma Latch joined us in the start-up zone this year, and we look forward to following the progress made by this collaboration. For your chance to meet potential partners at the Congress in Europe this October get your tickets here, and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Aug 22, 2024 | Technology |
Amid a rise in cases of antibiotic-resistant gonorrhoea, authors of a paper in Nature Communications present their research into the immune response gonorrhoea in the hope that it will enable the development of effective vaccines. They conducted a trial of 4CMenB in adults in coastal Kenya who have high exposure to Neisseria gonorrhoea (Ng), concluding that cross-protection provided by the vaccine against gonorrhoea could be explained by cross-reaction against a “diverse selection” of antigens derived from the outer membrane vesicles (OMV) component. The research was the result of a collaboration between scientists at the University of Manchester and Oxford and the KEMRI/Wellcome Trust Unity in Kenya.
Gonorrhoea vaccine challenges
Neisseria gonorrhoea (Ng) is the Gram-negative diplococcus that causes the sexually transmitted infection gonorrhoea. Approximately 82.4 million people were newly infected with Ng in 2020, which makes it the second most prevalent STI worldwide after Chlamydia trachomatis (CT). Gonorrhoea affects reproductive health and newborn well-being and is a “strong” co-factor in HIV transmission. Resistance to frontline antibiotics is “high and increasing”, so the development of an effective vaccine is an increasingly pressing need.
Vaccine development is complicated by the fact that infection with Ng does not usually induce protective immunity. Clinical trials of gonococcal vaccine candidates have “not been encouraging”. However, recent data suggest that an effective vaccine is “feasible”. A vaccine (MeNZB) derived from the related bacterium Neisseria meningitidis (Nm) had “most” efficacy but was linked to a reduction in gonorrhoea diagnoses. It is inferred that antigens within the Nm outer membrane vesicle (OMV) vaccine-elicited antibodies cross-reacted with gonococcal antigens.
4CMenB
GSK’s 4CMenB (Bexsero) combines an OMV preparation from the same Nm strain as MeNZB with five recombinant antigens; three of these are responsible for enhancing protection against Nm infection. The vaccine has demonstrated cross-protection against gonorrhoea and studies have identified a range of Ng OMV-derived proteins that “could play a protective role as target antigens” for antibodies induced through vaccination with 4CMenB.
The study
In the study the authors combine antigen microarrays with statistical and machine-learning methods to obtain a “comprehensive view” of how antigen reactivity profiles are linked to vaccination with 4CMenB and infection in a highly exposed human population. They selected a coastal Kenyan population that is at “high risk of infection”. 62 participants were screened to receive the vaccine 50 (37 men and 13 women) were enrolled and received their first vaccination. 47 participants (36 men and 11 women) received a second vaccination.
The researchers at University of Manchester identified the antibody response patterns and compared vaccine recipients with individuals infected with gonorrhoea. This has “important ramifications” for Ng vaccine design. For example, the “limited” protective effect of 4CMenB against gonorrhoea implies that cross-protection induced through meningococcal antigens, combined with OMV’s adjuvant properties, “could be responsible”. Of the four recombinant antigens examined, only NHBA is surface-exposed and “not likely to be solely responsible for protection”. Furthermore, the more durable responses to the OMV antigens indicate an environmental “adjuvant-like effect” that could lead to longer-lasting responses.
The authors note that antibody responses to certain antigens correlate, which suggests that a vaccine would not only demand the selection of component antigens and adjuvants, but a “consideration of how the whole formulation is able to induce long-lasting, protective immunity”. The University of Oxford’s Professor Chris Tang, project lead, describes the work as an “important step along the road to developing Ng vaccines”.
“We have a better idea of which responses are generated by partially protective vaccination compared with infection.”
Professor Jeremy Derrick from the University of Manchester identifies “wide implications” for “revisiting vaccine design for other bacterial pathogens using these new methods”. This is particularly important for those where antimicrobial resistance is a “problem”.
“We hope that the application of these technologies will enable progress towards vaccines against other pathogens.”
Join us at the Congress in Barcelona this October to hear more updates from vaccine experts on their progress against gonorrhoea, and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Aug 21, 2024 | Technology |
In August 2024 Touchlight announced that it is supplying its proprietary dbDNA to the University of Nottingham in support of the research and development of a next-generation DNA vaccine targeting Zika virus. The scientists at University of Nottingham are working on a Zika virus DNA vaccine that could be manufactured “within weeks” and deployed globally in future epidemics. While many DNA vaccines in development require devices to deliver the vaccine through the skin, the Nottingham researchers have identified a solution. Their proprietary DNA formulation can be given by a simple injection and uses synthetic manufacture instead of bacterial fermentation, shortening development time from 6 months to 6 weeks.
Rapid, efficient, scalable
Touchlight states that its enzymatic dbDNA technology represents a “breakthrough” in DNA production, offering a “rapid, efficient, and scalable” method for vaccine development. The dbDNA has the potential to reduce dose, eliminate antibiotic resistance, and provide a solution for low cost, stable vaccines for the developing world. Named after its schematic structure, doggybone DNA (dbDNA) is a “minimal, linear, double stranded, and covalently closed DNA construct”. It can encode long, complex, or unstable DNA sequences and has a “strong” expression profile.
DNA vaccines
DNA vaccines can be produced “rapidly and cheaply” and don’t require the same cold-chain storage as mRNA vaccines. Therefore, DNA vaccines are “ideal” for outbreak responses, particularly in “less economically developed regions”. The project has been funded by the UK Department of Health and Social Care, within the UK Vaccine Network, which aims to develop vaccines for disease with epidemic potential in low- and middle-income countries.
University of Nottingham’s Dr James Dixon commented that the Touchlight technology “has enabled us to make rapid progress” and will allow the team to “produce large quantities of the DNA vaccine at speed”. This is “vital in pandemic prevention and our response to the deployment of vaccines in the developing world and globally”.
“It will be hugely exciting to complete the pre-clinical trials and take us into the final stages with clinical trials and seeing real-world impact.”
Touchlight Chief Operating Officer Dr Tommy Duncan is “thrilled” to support the team at Nottingham with “innovative dbDNA technology”.
“We are committed to enabling developers of DNA vaccines by providing rapid, high purity DNA for vaccines against emerging pathogens.”
We look forward to welcoming Touchlight to the Congress in Barcelona this October; get your tickets to join us there and don’t forget to subscribe to our weekly newsletters for vaccine updates.
by Charlotte Kilpatrick | Aug 20, 2024 | Technology |
Emergent BioSolutions announced in August 2024 that it is “proactively” working with WHO and the US government in response to the outbreak of mpox in Africa and has pledged to donate 50,000 doses of ACAM2000. The donation will be delivered with Direct Relief, a humanitarian relief organisation that has a “long history” of providing medical interventions to the Democratic Republic of the Congo (DRC) and other affected countries.
ACAM2000
ACAM2000 (Smallpox (Vaccinia) Vaccine, Live) is the primary smallpox vaccine designated for use in a “bioterrorism emergency”. Doses have been supplied to the US Strategic National Stockpile. It is indicated for active immunisation against smallpox disease for persons determined to be at high risk for infection. It is a single-dose vaccine administered via a bifurcated needle.
Emergent filed a supplemental Biologics License Application (sBLA) to the US FDA in 2023 to seek an expanded indication for ACAM2000 vaccine to include immunisation against mpox virus. This application includes human safety data and animal study data showing that ACAM2000 was effective in protecting against mpox virus exposure. Emergent has also responded to WHO’s invitation for an Expression of Interest for Emergency Use Listing.
Meeting demand
Dr Raina McIntyre, Professor of Global Biosecurity, NHMRC L3 Research Fellow, Head Biosecurity Programme, Kirby Institute, University of New South Wales Sydney, believes it will be “unlikely” that there will be enough supply of 3rd generation vaccines to control the epidemic in Africa, “given the demand in other countries”.
President and CEO, Emergent BioSolutions, emphasised that Emergent is “ready to scale up response efforts and partner with US and global public health leaders”. He reflected that “for years” the company has supplied ACAM2000 to the US and allied governments in “support of preparedness and stockpiling initiatives”.
“Currently, we have additional product already in inventory, with the ability to increase supply by approximately 40 million doses, if and potentially when needed. In the meantime, 50,000 doses of ACAM2000 vaccine will be donated to help control the outbreak across the African continent.”
Mr Papa concluded that increasing outbreaks of mpox around the world “should raise concerns and spur ongoing efforts” to produce and stockpile vaccines and other interventions to address all orthopoxviruses.
For the latest vaccine updates, don’t forget to get your tickets to the Congress in Barcelona this October, and subscribe to our weekly newsletters here!
by Guest Editor | Aug 20, 2024 | Technology |
This is a guest post, kindly authored by Giulia Balconi of Adjuvant Capital.
Earlier this month, Valneva (NASDAQ: VALN) and LimmaTech Biologics announced a strategic partnership to accelerate the development of a quadrivalent vaccine against Shigella, known as Shigella4V (S4V). Under this collaboration, LimmaTech will complete a Phase II Controlled Human Infection Model and a Phase II pediatric study in low- and middle-income countries, while Valneva will take over future clinical development, as well as CMC, regulatory approval, and commercialization. Thanks to this collaboration, S4V is poised to enter Phase III studies later in 2027.
Shigella is the second-leading cause of diarrheal mortality globally, with an estimated 80-165 million cases and up to 600,000 fatalities every year. Despite the high incidence, there is currently no approved vaccine widely available for Shigella, and current treatment remains symptomatic and mainly relies on oral replacement of fluids and salts, as well as administration of antibiotics. Over the past few years, an increase in antibiotic resistant infections has raised the attention of the global health community. Shigella was identified by the World Health Organization as one of the top priority pathogens for the development of a new vaccine and was also included in the most recent Gavi Vaccine Investment Strategy.
With a vaccine for Shigella potentially on the horizon, a step back in time might help illuminate how this vaccine—once considered a long-shot—has advanced to late-stage development. In 2015, GSK acquired GlycoVaxyn, a Swiss biotech focused on bioconjugation technology with a promising vaccine candidate targeting Shigella, which generated positive Phase I data in 2010. Following the acquisition, GlycoVaxyn’s operational research business spun-out into LimmaTech Biologics, a new entity designed to collaborate with GSK on future bacterial vaccine development.
In partnership with GSK, and with support from the Wellcome Trust, LimmaTech continued development, refining a 4-valent construct (S4V) targeting the most prevalent serotypes, which entered a Phase I/II clinical trial in Kenya in 2019, and secured non-dilutive funding from the Bill & Melinda Gates Foundation in December 2022.
With the Phase I/II study in Kenya ongoing, LimmaTech announced an in-licensing agreement with GSK last year to further develop and commercialize S4V for the target pediatric population as well as for travelers and military personnel in endemic regions. Shortly thereafter, LimmaTech closed a Series A financing led by renowned global health impact funds to support S4V development in addition to the company’s earlier stage pipeline, which aims to address the growing threat of antimicrobial resistance. In a matter of just over a year, a flurry of dealmaking has brought S4V into the spotlight.
Although there is much work left to do, the story of S4V reflects the difficulties and opportunities in developing vaccines for global health. Consequently, the recent activity surrounding the program highlights the need for closer collaboration among big pharma, biotech, global health funders, and institutional investors to ultimately drive the development of much needed vaccines for diseases that disproportionately burden low- and middle-income countries. Almost 15 years after the initial Phase I study, there appears to be a path forward for a Shigella vaccine that could have a tremendous global impact and bring hope for millions of patients in underserved markets.
Giulia Balconi, M.P.H., supports research efforts at Adjuvant Capital, an impact investment firm supporting life sciences technology companies focused on historically neglected diseases and maternal/child health. Note, Adjuvant Capital has provided funding to LimmaTech Biologics.
We’re grateful to Giulia for these insights into vaccine development! To join discussions about vaccine progress and collaborative efforts to improve global health, don’t forget to get your tickets to the Congress in Barcelona this October, and subscribe to our weekly newsletters for more expert insights.
