by Charlotte Kilpatrick | Oct 14, 2024 | Technology |
SK bioscience announced in October 2024 that it has signed an agreement to acquire a stake in Fina Biosolutions (FinaBio) with a $3 million investment. SK bioscience becomes FinaBio’s first and sole strategic investor with a goal of improving the immunogenicity and productivity of conjugate vaccines. This announcement is another example of SK bioscience’s investment in global companies to “create synergies in business” after recently completing the acquisition of a controlling stake in IDT Biologika. The company states that it is securing its “competitiveness” through strategic investments in “promising companies with exceptional technology” and M&As to “lay the foundation for a great leap forward into a leading global company”.
FinaBio’s technology
Founded in 2006, FinaBio seeks to “help emerging market vaccine manufacturers learn to make affordable protein polysaccharide conjugates for vaccines”. It is now a “premier provider” of laboratory and consulting services, specialising in the research and development of conjugate vaccines for pneumoniae, meningococcal, typhoid, and other diseases. One of FinaBio’s key assets is FinaXpress, a proprietary E. coli expression system, that can produce proteins not previously made in the bacteria, like the carrier protein CRM197. FinaBio has expanded access to this protein, marketed as EcoCRM.
FinaBio is also developing a next-generation conjugation technology that is site-specific and targets the desired location for antigen binding. This is intended to boost immunogenicity and productivity. Supplying conjugation technology and carrier proteins to various global biotech companies and institutions, FinaBio continues to expand its business units.
A conjugate collaboration
SK bioscience will use FinaBio’s CRM197 technology in its efforts to “secure the high effectiveness of diverse conjugate vaccines while increasing profitability through high-yield processes”. CEO and President of SK bioscience Jaeyong Ahn is “delighted to continue developing partnerships with global firms that have next-generation vaccine technology”.
“Through our mid- to long-term collaboration with FinaBio, we will advance the vaccines we are developing to the next level and strengthen our competitiveness for global market expansion.”
Dr Andrew Lees, Founder and CEO of FinaBio, apprecitaes SK’s “confidence” in the organisation and support of accelerated global commercialisation of EcoCRM.
“Combined with our efficient conjugation technology, this will enable the development of the next generation conjugate vaccines. It will also allow us to continue our mission of promoting affordable vaccines.”
We look forward to welcoming FinaBio back to the exhibition floor at the Congress in Barcelona later this month; get your tickets to connect with their team there and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Oct 11, 2024 | Technology |
Orlance, Inc., announced in October 2024 that it has been awarded a National Institutions of Health (NIH) Fast Track Small Business Innovation Research (SBIR) grant to develop an Enhanced Seasonal Influenza Vaccine that provides “better protection against disease” even in years when there is a mismatch between predicted and actual circulating strains. The award includes $300,000 for Phase I; the total funding for the Phase I and II combined programme amounts to $3.3 million. The grant enables Orlance to leverage its innovative MACH-1 powdered vaccine and immunotherapy platform to address both seasonally changing and highly conserved influenza immunogens.
MACH-1 for influenza
MACH-1 is a high-performance microparticle ‘gene gun’ technology that “efficiently and uniquely” delivers DNA or RNA vaccine-coated microparticles into cells in the epidermis, which is “rich in immune stimulating cells”. An advantage of this technology in comparison with currently licensed mRNA vaccines is that MACH-1-delivered vaccines are stable at room temperature and are painless and needle-free. These vaccines also offer protective levels of immunity with the “smallest doses yet achieved within the field”.
The grant will enable a project to address the limitations of current flu vaccines by broadening the number of influenza strains targeted in one vaccine. This means vaccine production can occur closer to influenza season and achieve a better match between predicted and actual circulating strains. It will also stimulate “more diverse types of immune responses” in systemic and localised cells. The programme builds on Orlance’s universal influenza vaccine, adding seasonally changing influenza antigens to maximise protection.
Excelling in the field
Orlance’s Head of Research and Development and Principal Investigator Dr Kenneth Bagley commented on the importance of the MACH-1 technology.
“The unique properties of MACH-1 delivery into the highly immune competent epidermis that generates potent systemic and local respiratory mucosal antibody- and T cell-mediate immunity, coupled with the large payload capacity of DNA vaccines, may allow for Orlance’s universal influenza vaccine to excel where other universal vaccines have failed.”
Kristyn Aalto, CEO of Orlance, recognised the “continued funding support” from NIH.
“[The] support of the MACH-1 platform including this enhanced seasonal influenza vaccine reinforces the potential impact and significant step forward MACH-1 can bring to vaccine technology.”
We welcome Kristyn to the Congress in Barcelona this month for the Mucosal and Alternative Delivery workshop; get your tickets to join us for this here, and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Oct 9, 2024 | Technology |
In October 2024, CEPI announced that it is awarding funding of up to £3.7 million to support researchers at the University of Sheffield as they seek proof-of-concept for RNAbox. RNAbox is a specialised process designed to scale up the production of mRNA vaccines at regional vaccine sites. It is “easily adaptable and automated”, with the potential to improve global pandemic readiness by enabling increased equitable access to various mRNA vaccines, as and when needed. It also could help speed up responses to future emerging outbreaks.
Addressing mRNA challenges
mRNA vaccines be “more rapidly tailored” to specific diseases or variants, and the technology “holds promise” for different illnesses, including emerging infectious diseases. However, mRNA vaccines are “expensive to manufacture at a high product quality” and require complex cold-chain storage and transportation infrastructure. This makes them “extremely difficult to deliver to remote areas or low-resource settings”.
The RNAbox presents a potential solution to these challenges through its bespoke manufacturing process, designed to overcome the need to deliver the vaccine by facilitating local manufacture at small production sites. The process will run continuously to create between seven and ten times more mRNA at a time and enable more efficient use of raw materials. RNAbox uses digital-twin technology, in which a virtual replica of the vaccine manufacturing process is modelled on a computer in real-time with smart sensors collecting data on the physical product.
CEPI’s interest
CEPI states that the “fast, optimised vaccine production is critical to the 100 Days Mission”. The investment will explore applying the technology to vaccine development for CEPI priority pathogens, including the viruses that cause deadly diseases like Ebola, Lassa fever, MERS, and Nipah. Ingrid Kromann, Acting Executive Director of Manufacturing and Supply Chain at CEPI suggested that the University’s “versatile” technology “builds on the ‘vaccine revolution’ experienced during the COVID-19 pandemic”.
“It aims to overcome a number of scientific hurdles which resulted in poorer countries facing devastating vaccine inequity by helping to make high-quality, low-cost vaccines quickly and easily close to the source of an outbreak.”
Dr Zoltán Kis, School of Chemical, Materials, and Biological Engineering at the University of Sheffield, reflected on the “importance of being prepared” with the “necessary tools”.
“We need to tackle outbreaks equitably around the world, as diseases can spread across country borders.”
The RNAbox will “accelerate the development of new vaccines” and “mass-manufacturing against a wide range of diseases”.
“This transformative technology can also be used to develop much-needed vaccines against a range of unmet needs during non-epidemic/pandemic times. In case of a new epidemic/pandemic, the RNAbox can be quickly adapted to produce vaccines to tackle outbreaks. This will enable vaccine development and manufacturing capacity locally in countries around the world to serve local needs.”
The researchers will work with vaccine manufacturers in low- and middle-income countries to ensure the technology is fit-for-purpose in lower-resource settings.
At the Congress in Barcelona this month we will hear from experts who are revolutionising mRNA vaccine production to ensure products are accessible. Join us there to learn more, and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Sep 25, 2024 | Technology |
MSD Animal Health announced in September 2024 that it is expanding the newly USDA-approved NOBIVAC NXT vaccine platform to include a best-in-class solution to protect cats against a common feline infectious disease, feline leukaemia virus (FeLV). Describing this technology as a “breakthrough scientific achievement”, MSD Animal Health indicated that the vaccine is expected to be available at veterinary clinics and hospitals in the autumn.
NOBIVAC NXT
The NOBIVAC platform is behind a portfolio of products with an “extensive range of vaccines” to protect companion animals against various diseases. NOBIVAC NXT FeLV is the first and only feline leukaemia virus vaccine built using the RNA-particle technology platform. It is designed to deliver “optimised protection”. It is a nonadjuvanted, low volume 0.5 mL dose vaccine that “harnesses the natural ability of the immune system” to generate a robust response.
NOBIVAC NXT FeLV is labelled effective against persistent viraemia and is indicated for the vaccination of cats aged 8 weeks or older. The American Association of Feline Practitioners (AAFP) recommends administration in two doses, 3 to 4 weeks apart. It follows the AAFP’s recommendations for extended duration protection with a proven 2-year duration of immunity (DOI).
Feline leukaemia virus
Feline leukaemia virus can be spread in a “multitude of ways”, including mutual grooming, fighting behaviour, or shared food. It poses “serious” health risks, but cats often show no symptoms when they are first infected. However, as it persists, the virus can lead to cancer, severe blood disorders, or other infections associated with a compromised immune system. Routine vaccination can help protect from potential illness.
Meg Conlon, DVM, executive director, veterinary professional services, MSD Animal Health, suggested that “nearly 4% of cats” in North America are affected by the disease. This is a “notable percentage when there have been guidelines for prevention in place for decades”.
“That’s why education and awareness of the importance of vaccinating against this disease is so important.”
Ian Tarpey, vice president, research and development, MSD Animal Health, is proud to extend the RNA-particle technology with a vaccine that “protects against one of the most persistent threats to our feline patients”.
“MSD Animal Health and our NOBIVAC brand have a rich history in vaccine innovation, and we’re continuing to prove our dedication to ensuring there are safe and effective treatment options for veterinary professionals with the latest development of NOBIVAC NXT FeLV.”
For the latest on veterinary vaccines at the Congress in Barcelona next month, get your tickets to join us here and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Sep 23, 2024 | Technology |
Evaxion Biotech announced the launch of an enhanced version of its clinically validated AI-Immunology platform in September 2024, with an update to the EDEN AI prediction model. Improvements to the model include toxin antigen prediction, which enables the development of improved bacterial vaccines. AI-Immunology allows Evaxion to simulate the immune system and create predictive models to identify and develop personalised and other next-generation immunotherapies. It uses advanced AI and machine learning technologies to design and develop vaccine candidates in response to significant unmet needs.
EDEN upgraded
The AI-Immunology platform can deliver a new target within 24 hours, with “robustly validated” predictive capabilities. The EDEN prediction model is one of five models within the AI-Immunology platform. It rapidly identifies antigens that will trigger a robust protective immune response against “almost any” bacterial infectious disease. The model is fully AI-driven and designed to identify vaccine candidates “faster and at a lower cost than current state-of-the-art methods”. EDEN enables a novel approach to vaccine development that supports efforts against the “rising global issue of antibiotic resistance”.
The latest version 5.0 features several updates:
- Novel bacterial toxin antigen predictor – Evaxion has trained new machine learning models to improve the accuracy and reliability of toxin antigen prediction.
- Expanded training dataset – The process for curating additional training data from published sources has been streamlined with retrieval-augmented generation with large language models, followed by manual domain expert curation.
- Advanced protein feature prediction – The team has developed a new building block for protein feature prediction using protein language models, enhancing the model’s architecture and capability to predict various protein characteristics.
CEO of Evaxion, Christian Kanstrup, described the launch of the model as an “important milestone” that strengthens the AI-Immunology platform.
“As one of the few truly AI-first TechBio companies, our AI-Immunology platform is at the forefront of innovation. We wil continue to invest in its development and refinement to further improve our ability to discover novel targets and develop advanced vaccines.”
We look forward to learning more about the AI-Immunology platform 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 more vaccine technology updates.
by Charlotte Kilpatrick | Sep 19, 2024 | Technology |
An article in Scientific Reports in September 2024 uses Digital Shadows to facilitate a comparison of recombinant DNA and in vitro (IVT) mRNA vaccine manufacturing technologies. The authors offer an assessment of which manufacturing platform is better suited for two types of vaccines. They suggest that recombinant DNA technology exhibits a higher Profitability Index, but mRNA offers faster high potency in short product development cycles.
Technical and economic benefits
Limitations in “traditional vaccines” have “speared” the development of novel technologies for antigens and monoclonal antibodies, including the recent use of recombinant DNA and RNA technologies in the COVID-19 pandemic. Recombinant DNA technology requires the insertion of a gene encoding the relevant pathogen or immunoglobulin sequence into a cell factory organism, which produces the antigen or antibody. RNA technology uses stoichiometric biochemical reactions to produce mRNA (messenger RNA) encoding the antigen or antibody, which is translated in vivo by the recipient’s cells.
Both mRNA and DNA technologies have “established proof of therapeutic effectiveness”. However, they differ in approach to obtaining the therapeutic protein of choice, which leads to different manufacturing processes. For recombinant DNA, the process is “time-consuming and expensive, requiring specialised laboratory facilities and trained personnel”. By contrast, IVT mRNA is understood to be “fast, flexible, and inexpensive”. This is offset by the need for cold transportation and storage to cater to the “instability and sensitivity” of the RNA molecule. Furthermore, IVT mRNA-based vaccine manufacturing has not been standardised.
Both technologies have “captured the global scientific interest” and present opportunities in the treatment of cancer and autoimmune diseases among others. However, the authors state that that there is no comparison of the two technologies on technical and economic levels.
The study
Digital Shadows are “enabling tools suitable to model a system in a fiat cyber-physical environment, delivering data flow abstractions of processing performance”. They are also used in the study to simulate and analyse the “technical merits and production costs” of each technology at given operating conditions. This allows the researchers to investigate root cause deviations and evaluate the cost-effectiveness scenarios of each proposed solution.
The authors constructed Digital Shadows to compare recombinant manufacturing of monoclonal antibodies and antigens with IVT mRNA production processes. They developed algorithmic threads to explore strengths and weaknesses, offering “enabling tools of strategic decision planning”.
The research suggests that recombinant production methods create “highly stable and therefore advantageous products”, with a proven track record of clinical safety and efficacy, and a low risk of unknown side effects, carrier-related allergic reactions, and withdrawals. The vaccines require “minimal maintenance” to preserve stability and functionality, which “ameliorates any respective logistical challenges and minimises the risks related to post-production regulatory withdrawals”. The components needed for production are “accessible” for the pharmaceutical industry but may come under pressure in case of pandemic outbreaks.
A drawback of the recombinant DNA vaccine production platform is its “complicated and therefore difficult-to-automate sub-processes”. The technology requires additional personnel for “process supervision and control purposes”. The platform is therefore “less appropriate for encountering pandemic bursts” or tracking mutations.
Another concern is the high risk of material contamination in cellular protein production, particularly in upstream processing. If contamination occurs, the cell line and its products are discarded, which causes delays and financial losses. Alongside this risk, recombinant DNA and protein production methods feature “low production yield”, which means that raw and side materials are purchased at high quantities and handled by expert personnel to reach the necessary production capacity.
IVT mRNA manufacturing protocols have “strong competitive advantages” in some characteristics. Although the vaccine is “highly sensitive to environmental conditions”, the production process is “easier to standardise, automate, adapt, and operate in continuous mode” thanks to the synthetic chemical nature of its sub-processes. The biochemical section of related processes can offer a “less complex, more effective” alternative with minimal requirements. This reduces the risks of cross contamination and quality-related batch rejections, producing higher yields and limiting product losses; it also lowers raw material processing resources and reduces development time.
Conclusions
For monoclonal antibody products, the study showed that recombinant DNA technology had a higher Profitability Index than IVT mRNA manufacturing. While the recombinant DNA monoclonal antibodies require a significantly higher dose due to an inferior potency profile, this is not reflected analogously in the final production cost. IVT mRNA manufacturing also had “higher dependencies” on raw materials.
When considering antigenic vaccines, the authors found that recombinant DNA technology demonstrated “higher economic performance”, demanding reduced capital resources. It also encompasses “proven, well-grounded protocols” for process development. Recombinant manufacturing “appears advantageous” by meeting technical and financial expectations. However, IVT mRNA “significantly” shortens the timeline from development to clinical application and benchtop to scale manufacturing. It also offers “unparalleled advantages” in synthetic processes and reduced requirements for installing large-scale production equipment.
The paper concludes that clinical trials and field practice will reveal if mRNA technologies can offer non-inferior therapeutic results compared to their DNA recombinant established alternatives. If you have worked with either of these technologies, what are your impressions or predictions? Why not join us at the Congress in Barcelona next month to share your insights into various platform technologies, and don’t forget to subscribe to our weekly newsletters for the latest vaccine news.
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 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 | Jul 29, 2024 | Technology |
In July 2024, WHO announced that Argentine manufacturer Sinergium Biotech is to lead a new project that aims to accelerate the development and accessibility of human avian influenza (H5N1) mRNA vaccine candidates for manufacturers in low- and middle-income countries (LMICs). The project will leverage the WHO and Medicines Patent Pool (MPP) mRNA Technology Transfer Programme, which was launched in July 2021 to build capacity in LMICs for the development and production of mRNA-based vaccines. Sinergium is a partner in the Programme and has developed candidate H5N1 vaccines. If it establishes preclinical proof-of-concept the technology, materials, and expertise will be shared with partners, “aiding the acceleration” of the development of these candidates and “bolstering pandemic preparedness efforts”.
The mRNA Technology Transfer Programme
Since its inception, the mRNA Technology Transfer Programme has already developed and implemented a platform that has been used to establish the immunogencity, efficacy, and safety of a COVID-19 vaccine candidate in preclinical models. The platform was created and validated at Afrigen and is now being shared with partners for applications against “other critical disease targets”.
WHO Director General Dr Tedros Adhanom Ghebreyesus, states that the initiative “exemplifies” why WHO established the Programme to “foster great research, development, and production”.
“When the next pandemic arrives, the world will be better prepared to mount a more effective and more equitable response.”
Charles Gore, MPP’s Executive Director, reflected that the goal of the Programme is to “enable low- and middle-income countries to lead development efforts, foster collaboration, share resources, and disseminate knowledge”.
“This project embodies our vision and demonstrates a strong commitment to future pandemic preparedness and response.”
Rising to the avian influenza challenge
WHO states that avian influenza viruses are a “significant public health risk” due to “widespread circulation in animals” and “potential to cause a future pandemic”. Thus, the latest project complements work to improve and strengthen the sharing of influenza viruses with human pandemic potential and increase LMIC access to vaccines. Dr Jarbas Barbosa, Director of the Pan American Health Organisation (PAHO), is pleased with the news.
“This announcement underscores the importance of not only geographically diversifying the innovation and production of health technologies including and recognising the capacities in Latin America and the Caribbean, but also the importance of early planning for access and the sharing of knowledge and technologies during the research and development processes.”
Chief Executive Officer at Sinergium is “excited to tackle this public health challenge” in collaboration with partners.
“Sinergium’s enhanced capacity and readiness to apply our expertise to H5N1 will play a vital role in this effort towards global pandemic preparedness. I would also like to thank PAHO who have also been instrumental through the strong support it offers to regional manufacturers in the Americas.”
The importance of technology transfers in building regional capacity and facilitating equitable vaccine distribution will be discussed in a panel 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 | Jun 5, 2024 | Technology |
In June 2024 a team from Monash University shared that a collaboration with the Yong Loo Lin School of Medicine at the National University of Singapore (NUS Medicine) has produced a COVID-19 vaccine that has induced “very long-lasting, protective immunity” against SARS-CoV-2 virus in pre-clinical models. Their paper in Molecular Therapy presents a novel vaccine platform that fuses the receptor-binding domain (RBD) from the SARS-CoV-2 virus spike protein to the Clec9A antibody, which targets a specific subset of dendritic cells. A single shot immunisation resulted in “increased protection over time”.
The need for new vaccines
The authors suggest that safe and effective vaccines are “imperative” to protect “not only against death, but also against long term, debilitating conditions associated with SARS-CoV-2 infection”. Although more than 13 billion doses of COVID-19 vaccines have been administered globally, they face “several challenges”. For example, repeated booster doses are required as SARS-CoV-2 reactive antibodies and T cells “waned over time”.
“New-generation vaccines that can overcome at least some of these limitations are needed to provide broad and durable protection against rapidly evolving SARS-CoV-2 variants.”
Previous research has explored the potential of dendritic cell (DC)-based vaccines, including antigen-pulsed autologous DC and DC-targeting strategies. Targeting antigen vaccine candidates to Clec9A expressed on the type 1 conventional DC (cDC1) subset has “proven promising” in pre-clinical studies. Clec9A is a C-type lectin-like receptor that acts as a damage recognition receptor, identifying filamentous actin exposed when the cell membrane is damaged and facilitates the cross-presentation of dead cell-associated antigens.
Clec9A targeting was found to be “more potent” than targeting of other DC receptors. In the study, the authors engineered a Clec9A-RBD antibody construct by genetically fusing a single copy of ancestral SARS-CoV-2 receptor binding domain (RBD) to each heavy chain of a rat IgG2a mAb specific to mouse Clec9A.
Study findings
In their study, the authors demonstrate that targeting SARS-CoV-2 RBD to Clec9A-expressing DCs (cDC1) resulted in “potent and exceptionally sustained immune responses” after single dose immunisation.
“Importantly, we provided evidence of affinity maturation over time, which led to improved potency and breadth of the humoral immune response against a broad representation of the sarbecovirus family.”
Associate Professor Sylvie Alonso, Principal Investigator of the study, described the results as “very promising”, with the expectation that the work in pre-clinical models is “highly translatable to humans”.
“Our teams in NUS Medicine and Monash University foresee that the exceptional durability of the immune responses induced by the Clec9A targeting technology, when used as a booster vaccine strategy, may address the shortcoming of current mRNA vaccines, chief of which is the rapid waning of immune responses.”
Associate Professor Alonso stated that the next step is to evaluate the vaccine candidate as a booster vaccine in mRNA-vaccinated pre-clinical models.
“We hope to demonstrate that this booster approach will induce long-term protective immunity and avoid the need of multiple (annual) booster shots. Beyond COVID-19, this versatile, rapidly deployable vaccine platform shows promising potential to be part of the pandemic response against diseases caused by unknown pathogens in the future.”
Associate Professor Mireille Lahoud emphasised the “strength of our platform targeting specialised immune cells for vaccine improvement”.
“There remain many diseases where effective vaccines have proven difficult to generate. Validation of this platform provides strong proof-of-concept for application to such challenges.”
For more on vaccine technology and innovation, why not join us at the Congress in Washington this October or subscribe to our weekly newsletters here?
by Charlotte Kilpatrick | Jun 3, 2024 | Technology |
Moderna announced in May 2024 that the US FDA has approved mRESVIA (mRNA-1345), its mRNA respiratory syncytial virus (RSV) vaccine, for the protection of adults aged 60 years and older from lower respiratory tract disease caused by RSV infection. This approval was granted under a breakthrough therapy designation and is the second mRNA product from Moderna to be approved. It is based on positive data from a Phase III clinical trial, ConquerRSV.
RSV is a “highly contagious” seasonal respiratory virus, a “leading cause” of lower respiratory tract infections and pneumonia that causes a “particularly large burden of disease” in infants and adults. Every year between 60,000-160,000 older adults are hospitalised and 6,000-10,000 die due to RSV infection. Moderna hopes to have the vaccine available for eligible populations in the US by the 2024/2025 respiratory virus season.
mRESVIA
The vaccine comprises an mRNA sequence encoding a stabilised prefusion F glycoprotein, which is expressed on the surface of the virus and is required for infection by helping the virus to host cells. Moderna states that the prefusion conformation of the F protein is a “significant target of potent neutralising antibodies” and is “highly conserved” across both RSV-A and RSV-B subtypes. The vaccine uses lipid nanoparticles (LNPs) like the Moderna COVID-19 vaccines.
The FDA’s approval of mRESVIA is based on data from the ConquerRSV study, which enrolled around 37,000 adults aged 60 or older across 22 countries. The primary analysis with 3.7 months of median follow-up found a vaccine efficacy against RSV lower respiratory tract disease (LRTD) of 83.7%. During the FDA review a follow-up analysis of the primary endpoint took place, with “consistent” results. Further longer-term analysis showed “continued protection” against RSV LRTD over 8.6 months median follow-up.
“No serious safety concerns were identified in the Phase III trial.”
Strength and versatility
Moderna’s CEO, Stéphane Bancel, commented that the FDA approval “builds on the strength and versatility” of the mRNA platform.
“mRESVIA protects older adults from the severe outcomes of RSV infection, and it is only RSV vaccine available in a pre-filled syringe designed to maximise ease of administration, saving vaccinators’ time and reducing the risk of administrative errors.”
Bancel stated that the approval is the first time an mRNA vaccine has been approved for a disease other than COVID-19.
“With mRESVIA, we continue to deliver for patients by addressing global public health threats related to infectious diseases.”
To participate in discussions about managing RSV through vaccination, why not join us in Barcelona for The World Vaccine Congress this October? Don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | May 31, 2024 | Technology |
Next from our series of conversations with experts at The World Vaccine Congress in Washington is an interview with Dr Antu Dey from Icosovax, part of the AstraZeneca group. Dr Dey joined us in the Emerging and Re-Emerging Diseases track to present “A novel VLP platform technology for development of vaccines against emerging and re-emerging diseases”. Dr Dey heads preclinical research for the AstraZeneca Early Vaccines & Immune Therapies team, leading discovery and research of vaccine candidates.
A novel VLP platform
We begin with a question about Dr Dey’s session, and he kindly emphasises that it covered “truly a novel VLP platform technology“, which came out of a collaboration between the Gates Foundation and David Baker and Neil King’s lab at UW.
“What seemed to be really a fascinating protein-based nanoparticle technology has revolutionised how we can present antigens from various pathogens, be it viral, bacterial, or others.”
It has already demonstrated an ability to generate a “really strong vaccine immune response”. This is what is “at the very backbone” of the bivalent vaccine that AstraZeneca is taking forward and other targets for other indications.
Challenges with disease targets
We then asked Dr Dey about any challenges that are associated with tackling emerging and re-emerging diseases, which he suggests is an “important and timely” consideration. He reflects that, when a pathogen emerges in humans, it demands a lot of discovery efforts to design, develop, and evaluate an effective vaccine candidate against the pathogen in pre-clinical settings. However, as the pathogen interacts with the host and environment it goes through mutations, which “pose challenges to the vaccines that we develop at the beginning”.
“Therefore, we need to adapt.”
In response to this need to adapt, Dr Dey and team look at changes within the pathogen, “particularly in those proteins that mediate entry into host cells” to ensure that the vaccine antigen is updated.
More on rising to the challenge
Our penultimate question considers how the team at AstraZeneca is tackling these challenges and updating the vaccine in case of re-emergence of these pathogens, which Dr Dey suggests demands a more “technical” answer!
“What we do is look at the evolution of the pathogen, at the same time we now drill down into the impact of these evolutions…and then go into the changes.”
While those changes are “necessary” for vaccine updating, the team explores “what elements” need to be kept in consideration.
“We go into what are called conserved epitopes, or regions, within the antigen, that need to be maintained.”
The vaccine antigen must then be presented in a way that the immune system can respond effectively. While this is happening, antigens can become “more and more difficult to make” from an expression or stability standpoint.
“My team spends an incredible amount of time in understanding those changes and how those changes not only impact the pockets, or the epitopes that have altered, but also how those changes now impact expression difficulties and conformational stability difficulties, and then we try to bring in protein changes, or protein engineering changes, into those antigens, stabilise them, and then update our vaccine accordingly.”
Why WVC?
Finally, we invited Dr Dey to share his intentions or expectations for the event. He suggests that it’s “two way”. To start with, he joined us to share the “journey” of their technology and the “potential beyond what we have done today”. The second part was to learn from colleagues and take lessons from others in the emerging disease space.
“That should help us, either to collaborate or to have those learnings into our vaccine design to take things forward.”
It was great to speak to Dr Dey and we hope that you enjoy the conversation!
For more conversations with our experts from the Congress in April do make sure you subscribe for weekly updates here!
by Charlotte Kilpatrick | May 30, 2024 | Technology |
Researchers from University of California, Berkeley, shared research in Nature that demonstrates the complete biosynthesis of QS-21 in engineered yeast strains. QS-21, the only saponin-based adjuvant that has been clinically approved for use in humans, has “limited” availability. Through their work, the team hope to “enable the rational design of potent vaccine adjuvants”.
QS-21
The authors suggest that alum has been the “most widely used, clinically approved” vaccine adjuvant since its discovery in the 1920s. However, QS-21 has also been shown to “exhibit potent immunoactivity”. It has been used in GSK’s Mosquirix and Shingrix as well as Novavax’s COVID-19 vaccines and has been tested in “more than 120 clinical trials”.
“Despite major commercial interest, the availability of QS-21 remains limited, owing mainly to its structural complexity.”
It comprises four distinct structural domains:
- A lipophilic triterpenoid core, quillaic acid
- A branched trisaccharide moiety on the C3 position
- A linear tetrasaccharide chain on the C28 position
- An unusual pseudodimeric acyl chain capped by an arabinofuranose
QS-21 is “traditionally” extracted from the tree bark of the soapbark tree, Quillaja saponaria, native to Chile. Isolation is “complicated” due to the “multitude” of different strcuturally related Quillaja saponins; the purification process is “highly laborious and low yielding”.
“Developing alternative production processes that are more sustainable and scalable would help to meet the ever-increasing demand for potent vaccine adjuvants, and to address existing or emerging medical needs.”
In the paper, the researchers present the complete biosynthesis of QS-21-Api and QS-21-Xyl, alongside structural derivatives in Saccharomyces cerevisiae, from simple sugars. This was achieved by upregulating the yeast native mevalonate pathway to provide a high carbon flux towards 2,3-oxidosqualene, which was then cyclised by heterologous β-amyrin synthase and site-selectively oxidised by plant cytochrome P450s to yield the aglycone of QS-21, QA.
The introduction of plant nucleotide sugar synthetic pathways made seven non-native uridine diphosphate sugars (UDP-sugars), which are used to add sugars onto the C3 hydroxy and C28 carboxy functional groups of QA through co-expression of QS-21 pathway glycosyltransferases (GTs). An engineered type I polyketide synthase (PKS), two type III PKSs, and two stand-alone ketoreductases (KRs) were expressed in yeast to create the dimeric acyl unit that “constitutes the last step” before the terminal arabinofuranose addition to yield QS-21. In the engineered yeast, pathway enzymes and their functional homologues were expressed.
The authors state that this combinatorial approach enabled selection of activities that function optimally together in a yeast cell, which enabled the production of QS-21.
The result
The final strain contains 38 heterologous enzymes from six species across several enzyme families, and to achieve the complete biosynthesis of QS-21 the team mimicked the subcellular compartmentalisation of plants from the ER membrane to the cytosol.
“QS-21-Xyl and QS-21-Api – two isomers of QS-21 with high structural similarity – can therefore be produced in separate yeast strains, and this enables them to be purified, and their immunogenicity to be characterised, in an independent manner.”
The authors argue that the platform provides “vast opportunities” to produce structural variants of QS-21. Furthermore, as the traditional method of extraction and purification destroys the bark of the tree, it has provoked “increased governmental regulations around its deforestation”. Thus, the method “highlights the possibility of replacing the plantation-based supply of saponins” with “industrial fermentation at scale”.
Addressing a need
Professor of chemical and biomolecular engineering, Jay Keasling, commented that during the pandemic, public health experts were “really worried” about the availability of QS-21 “because that only comes from one tree”.
“From a world health perspective, there’s a lot of need for an alternative source of this adjuvant.”
He is “gratified” that synthetic biology has “come so far” that “we can now build a pathway to produce a molecule like QS-21″.
“It’s a testament to how far the field has progress in the last two decades.”
Postdoctoral fellow Yuzhong Liu, first author, shared that this research “highlights the power of synthetic biology to address both major environmental, as well as human, health challenges”.
For more insights into vaccine technology and development, why not subscribe to our weekly newsletters here?
by Charlotte Kilpatrick | May 28, 2024 | Technology |
In May 2024, the University of Pennsylvania announced that its researchers have published research in Nature Communications that suggests potential in an experimental mRNA vaccine against avian influenza virus H5N1. The team believes that mRNA lipid nanoparticle (LNP) vaccines could be useful in the event of an influenza virus pandemic as they can be “rapidly” produced and “do not require the generation of egg-adapted vaccine seed stocks”. They therefore show that a monovalent mNRA-LNP vaccine that expresses 2.3.4.4b H5 is “immunogenic and protective in pre-clinical animal models”.
An increasing need
The authors state that highly pathogenic avian influenza (HPAI) H5 viruses of the A/goose/Guangdong/1996 (Gs/Gd) lineage “emerged in southeast Asia in 1996” and have “since spread geographically and diversified into several genetically distinct haemagglutinin (HA) clades”. Thanks to the long-distance migration of wild birds, these HPAI viruses have demonstrated “rapid transcontinental spread”. However, since 2020, Gs/GD lineage H5 viruses of clade 2.3.4.4b have “circulated at historically high levels” in both wild and domestic populations with “occasional human infections” and “increasing incidences” of spillover into mammals.
The study presents a monovalent mRNA-LNP encoding HA from a 2.3.4.4b virus, tested in mice and ferrets, to reveal that it is immunogenic and protective in these models. The team found that the vaccine “elicits robust antibody and CD8+ T cell responses in mice” and detected “high levels” of H5 antibodies 1 year after single vaccination. The vaccine also elicited neutralising antibodies and broadly binding HA stalk antibodies in both mice and ferrets. In challenge experiments the vaccinated ferrets cleared the virus “more rapidly” than unvaccinated controls, lost less weight, and displayed fewer clinical symptoms. All vaccinated animals survived, while the unvaccinated animals died after H5N1 challenge.
The researchers emphasise the importance of comparing the vaccine to other vaccine platforms. However, they highlight the “many potential benefits of mRNA-LNP based vaccines compared to inactivated vaccines” and reflect that the capacity to make mRNA-LNPs has “expanded widely” since the start of the COVID-19 pandemic.
“Notably, mRNA-LNP vaccines can be rapidly produced without first isolating and adapting viral strains that grow efficiently in fertilised chicken eggs or cell culture. It is now possible to start creating novel mRNA-LNP vaccines within hours of sequencing a new pandemic viral strain.”
More agility
Dr Scott Hensley, professor of Microbiology at the Perelman School of Medicine, worked with Dr Drew Weissman, Roberts Family professor in Vaccine Research and Director of Vaccine Research at Penn Medicine. Dr Hensley considered “previous influenza pandemics” such as the 2009 H1N1 pandemic, suggesting that “vaccines were difficult to manufacture and did not become available until after the initial pandemic waves subsided”.
“The mRNA technology allows us to be much more agile in developing vaccines; we can start creating an mRNA vaccine within hours of sequencing a new viral strain with pandemic potential.”
Dr Weissman commented that “before 2020, experts thought the influenza virus posed the greatest risk of causing a pandemic”. However, we had “limited options for creating a vaccine if that had happened”.
“COVID-19 showed us the power of mRNA-based vaccines as tools to protect humans from emerging viruses quickly, and we are better prepared now to respond to a variety of viruses with pandemic potential, including influenza.”
To be part of essential discussions about managing avian influenza at The World Vaccine Congress in October, get your tickets here, and don’t forget to subscribe for more vaccine insights here.
by Charlotte Kilpatrick | May 28, 2024 | Technology |
Our next interview guest from The World Vaccine Congress in Washington is Dr Micha Roumiantzeff, CEO and President at MICHADVICES. In January 2023 he created a small, non-profit company MICHADVICES to offer his services as well as his address book to all companies developing human and veterinary vaccines. With MICHADVICES he hopes to do “something usfeul”. Dr Roumiantzeff has more than 60 years of experience in vaccinology, for animal and human vaccines and biological products. From 1962 to 1995, he worked with the Mérieux Group, for animal vaccines and biological products then human vaccines and biological products. He has been involved in R&D, production, and distribution. After working with the Mérieux Group, he became a vaccine expert with WHO and the European Commission.
Addressing challenges
We begin by considering the challenges that Dr Roumiantzeff addresses with MICHADVICES. He explains that he has “four platforms”. The 1st provides advice: “how to make a vaccine”.
“It’s a long process. People sometimes have very nice, very beautiful ideas, and they believe that it is very easy to reach. But in fact, it’s a very, very difficult barrier.”
Dr Roumiantzeff explores the many “hurdles” to jump, such as identifying a “source” or finding the right antigen. Other steps include purification, formulation, and production. He reflects that “many vaccines” are fragile and demand specific temperatures. However, he refers to ApiJect, who have “solved the problem”! Check out our interview with Dr Kelley here to learn more.
The 2nd platform came from his “history” as an expert with WHO and the European Commission.
“I knew a lot of people! So, I have more than 4,000 addresses…I open the door.”
This platform does not provide funding, but connection to organisations such as CEPI, the Bill and Melinda Gates Foundation, and IVI. The 3rd platform is “how to obtain money”.
“Sometimes this is a problem. It’s very expensive to develop a product.”
Here, again, Dr Roumiantzeff is able to connect his clients to support. The 4th platform is “devoted to mRNA vaccines”. He recalls discovering the name Katalin Karikó at the start of the pandemic, and following her story from early beginnings to Nobel Prize acclaim, and is fortunate to have established excellent relationships with Katalin. His account (linked at the bottom of this article), concludes that the “prince” of this tale was the Nobel Prize!
Why WVC?
As always, we conclude our interviews with a question about the event, and the reasons that our experts have joined us. For Dr Roumiantzeff, who attends many events each year, these are the best!
“The ones from Terrapinn are the best for documentation, contact, follow up…they open the door.”
A last word: ApiJect
Dr Roumiantzeff concludes his interview with a shout-out to ApiJect, ApiLabs, who he met at the Congress in Santa Clara in 2023.
“All my life, I wanted to bring the vaccines to remote rural areas, in Africa, Asia, Central and South America. It was almost impossible.”
However, ApiJect have a “very simple” system to remedy this: the Prefilled ApiJect Injector system.
“I am absolutely fond of them!”
It was lovely to speak to Dr Roumiantzeff, and we hope that you enjoy the interview!
For more conversations with our experts from the Congress in April do make sure you subscribe for weekly updates here!
Dr Roumiantzeff’s “Fairytale”:
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by Charlotte Kilpatrick | May 24, 2024 | Technology |
In May 2024 SpyBiotech announced a sponsored research agreement with the University of Oxford for the development of a vaccine against Epstein-Barr virus (EBV). The project is to combine Oxford’s “groundbreaking” academic research capabilities with SpyBiotech’s proprietary SPYVLP platform technology to advance three vaccine candidates to Phase I clinical trial. EBV is a “commonly spread virus” that can cause “several serious health conditions”, such as infectious mononucleosis, and is linked to various cancers and multiple sclerosis.
EBV
Epstein-Barr virus (EBV) is one of the most commonly spread human viruses, transmitted through saliva. While many people recover within a few weeks, for some individuals it can lead to “a number of health conditions”. Indeed, research has linked people with multiple sclerosis and some lymphomas to infection with the virus.
SPYVLP
SpyBiotech’s technology addresses current complications with virus-like particle approaches to vaccine development. It can split a protein from the common bacterium Streptococcus pyogenes into two parts:
- The SpyTag peptide can be bound to antigens and its partner protein SpyCatcher
- SpyCatcher binds to the VLP
The two components bind together in a “spontaneous conjugation forming an unbreakable covalent bond”. The process is “rapid, efficient, irreversible, and extremely versatile”. Under the terms of the agreement, SpyBiotech will provide access to this platform to Oxford researchers.
An important step
Mark Leuchtenberger, CEO at SpyBiotech, believes the collaboration is an “important step forward on a commonly spread virus” that has “no currently available vaccines or therapeutics for its prevention or spread”.
“We see a great need for a vaccine against EBV.”
President and CSO of SpyBiotech, Dr Sumi Biswas, is “keen to progress these vaccine candidates” with Professor Sandy Douglas and his team at the Jenner Insitute, after the generation of “promising” pre-clinical data.
For the latest on innovative technology and vaccine partnerships don’t forget to get your tickets to The World Vaccine Congress in Barcelona this October or subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | May 24, 2024 | Technology |
CEPI announced in May 2024 that it is supporting researchers from the University of Oxford on a project called ‘PREpare using Simulated Trial Optimisation (PRESTO)’. The scientists will use computer simulations to “generate important insights” on how vaccine clinical trials can be used to stop the spread of an emerging outbreak. CEPI is contributing $2.4 million to the Pandemic Sciences Institute; the diseases tested in this project are on CEPI’s priority list and WHO’s R&D Blueprint: Nipah, Chikungunya, Lassa, Rift Valley fever, Ebola and related viruses, Coronaviruses, and ‘Disease X’.
Getting a head start
Dr Richard Hatchett, CEO of CEPI, commented that as an outbreak occurs, we will not have time to “get all the information we need to tell us how best to conduct pivotal clinical trials”.
“Mathematical modelling can give us a head start by forecasting how a worrisome virus might spread and what we need to do to respond.”
The project’s optimal study designs will “allow health officials to make quick, informed decisions on the best steps” towards “more efficient vaccine testing and rapid evidence generation”. This will improve and accelerate the outbreak response.
Data generated in existing CEPI-funded research will be fed into a computer model with evidence from previous outbreaks to create hypothetical scenarios that investigate a selected virus. The findings from these scenarios will be used in analysis sheets that “rank the suitability of different clinical trial options”. CEPI offers the example of recommending a randomised controlled trial or a vaccination trial.
The project will span three years and begins with models of Nipah. Should an outbreak of Disease X occur, the team will direct their efforts to the emerging pathogen, making clinical trial data “rapidly available” to enable faster public health response efforts. The computer software will also be shared on an open-source platform and developed in a “modular manner” to allow external researchers to run tests and update the tool with new data.
100 Days Mission
This project aligns with CEPI’s 100 Days Mission by preparing clinical trial frameworks before an outbreak occurs. Professor Christophe Fraser, Professor of Infectious Disease Epidemiology at the Pandemic Sciences Institute, emphasised that “ensuring vaccines can be robustly tested at speed is critical” in efforts to “better respond” to future pandemic threats.
“With every day of delay potentially costing many lives, and with the recent experience from COVID-19, we now have an opportunity to develop improved vaccine clinical trial designs so we can hit the ground running in a disease outbreak.”
Professor Fraser states that the PRESTO project will bring together mathematical modellers, ethicists, regulators, vaccine manufacturers, and field teams to “study what works with different pathogens in different settings”.
“Our aim isn’t to find the theoretical abstract best solution, but to develop models that allow decision-makers to explore the impact of the inevitable trade-offs that they will have to make in different settings.”
For more on technology to facilitate better pandemic preparedness, why not subscribe to our weekly newsletters here?
by Charlotte Kilpatrick | May 23, 2024 | Technology |
A study in npj systems biology and applications in April 2024 presents an approach for “identifying and prioritising vaccine antigens” using a machine learning-based reverse vaccinology strategy to predict potential new malaria vaccine candidate antigens. The team behind the paper comprises computational biologists at the University of Maryland, College Park, and researchers at the University of Maryland School of Medicine in Baltimore. Not only did they identify new potential targets but were able to rank them based on performance.
A malaria need
The authors recognise “substantial reductions in the malaria burden in many endemic areas” thanks to artemisinin-based combination therapies and other tools.
“However, progress toward malaria elimination has stalled as malaria incidence has plateaued and gains have been threatened by the emergence of resistance to interventions in the parasite and vector.”
The role of malaria vaccines in elimination efforts will be “critical”. Transmission of Plasmodium parasites occurs after infective mosquitoes take a blood meal and inject sporozoites, which then develop and multiply in the liver. Vaccines are “meant to block infection” against this pre-erythrocytic stage. Once the Plasmodium merozoites emerge from the liver they “invade and replicate inside red blood cells”. This stage of the life cycle causes malaria disease and death, which blood-stage vaccines are intended to “limit”. Vaccines that block transmission would “inhibit parasite sexual reproduction and development in the mosquito”.
“Design of a broadly protective malaria vaccine has been hampered by several factors, including multiple parasite life stages that express different antigens, extensive genetic diversity within individual antigens targeted by vaccines, partial natural immunity that is short-lived and non-sterilising, and incomplete knowledge of immune correlates of protection.”
Malaria parasites, haploid in humans and “briefly” diploid in mosquitoes, have extensive genetic variation “generated through mutation during mitotic reproduction in humans and by sexual recombination in the mosquito”. Although the first P. falciparum genome was shared in 2002, most vaccine development efforts have focused on a “small number of highly diverse vaccine candidates”. These have been identified through “traditional” vaccinology approaches, in contrast to a “more comprehensive, genome-level approach”.
Reverse vaccinology
A strategy first proposed by Dr Rino Rappuoli is reverse vaccinology, which uses bioinformatics approaches to identify pathogen antigens or epitopes that can serve as vaccine candidates. It has been used in the identification of several vaccine antigens for bacterial and viral pathogens.
“The wealth of systems data available for P. falciparum lends itself to the use of reverse vaccinology to identify new malaria vaccine antigens, which may allow identification of less immunodominant but more conserved antigens that have been misused using traditional vaccinology approaches.”
This, the authors suggest, is where machine learning will be useful; it doesn’t require a priori assumptions about the importance of specific criteria, but “learns” protein properties most associated with vaccine potential. Positive-unlabelled (PU) learning identifies potential positives among unlabelled entities “based on the properties of the positives”. It has been used to identify genes associated with human disease but not, as far as the authors are concerned, to identify candidate antigens.
In their study, the authors modify canonical positive-unlabelled random forest (PURF) to distinguish proteins with vaccine potential (antigens) from non-antigens, ranking candidates with probability scores.
What does the study find?
The authors chose random forest because of its “high predictive accuracy, high interpretability, and insensitivity to outliers, and predictive variable scales”. The approach identified “previously unknown vaccine candidate antigens” within a “flexible framework” that allows prioritisation. Candidate antigens were filtered based on gene essentiality, where mutations could affect parasite viability and help reduce parasite escape from vaccine-induced immune responses. Many of the candidate antigens were “predominantly” expressed in a single life stage, and those that were expressed in multiple life stages may be “attractive” because they would target multiple life stages. A summary report of the candidate antigens can be viewed here.
The approach is not limited malaria; the authors believe that the methodology can be “tailored and applied to other disease pathogens” and could inspire other scientific research areas. Professor Michael Cummings, one of the co-authors, commented that “these findings offer a flexible framework for future vaccine research”.
“We can adjust our criteria and even apply this approach to other diseases beyond malaria. It’s a big step forward in the quest for better vaccines.”
For the latest vaccine technology updates and insights into infectious disease management, why not join us at the Congress in Barcelona or subscribe to our newsletters here?
by Charlotte Kilpatrick | May 22, 2024 | Technology |
In May 2024, the University of North Carolina at Chapel Hill announced that it is leading a partnership with National Institute of Allergy and Infectious Diseases funding. The collaboration also involves Vaxcyte and the University of Chicago. The grant, worth $9.3 million, will enable scientists to “build on past vaccinology accomplishments to develop a viable vaccine candidate for early human clinical trials”.
Chlamydia
Chlamydia is a common and treatable sexually transmitted infection that affects “many millions of people around the world”. However, as many people do not experience symptoms or get tested, they may not know that they have the disease. Unfortunately, if left untreated, it can “seriously harm” the female reproductive system, making it “impossible or difficult to get pregnant” or leading to a “potentially fatal ectopic pregnancy”. The bacterium can also be transmitted to babies and cause eye infections and pneumonia.
A vaccine candidate
Dr Toni Darville, Distinguished Professor of Paediatrics and Microbiology & Immunology, division chief of paediatric infectious diseases, and scientific director of the Children’s Research Institute at the UNC School of Medicine, identifies a “clear unmet need” for a vaccine.
“Our previous studies of infected women and mice identified Chlamydial Protease Activation Factor (CPAF) as a strong vaccine candidate.”
A vaccine candidate would need “potent adjuvants” to modulate the immune response due to the nature of the female genital tract and “lack of secondary lymphoid tissue”. Chlamydia might also require mucosal vaccination to “ensure resident memory T cells are generated” against the bacterium before infection.
“Our earlier work showed that our new covalent CPAF-adjuvant conjugation approach enhanced cell activation, reduced toxicity, and improved immune response, leading to superior efficacy as well as reduced cost.”
Dr Jeff Fairman, vice president of research and co-founder of Vaxcyte, is “excited to explore our ability to successfully develop a Chlamydia vaccine candidate” to be advanced to early-phase human clinical trials.
“This grant will allow us to incorporate a tiered approach to determine if refinements using an innovative generation of molecules delivered via mucosal routes will enhance disease protection in animal models.”
For more updates on vaccine partnerships and investments, why not subscribe to our weekly newsletters here?
by Charlotte Kilpatrick | May 16, 2024 | Technology |
Our next interview from the Congress in Washington is a conversation with Vernal Biosciences‘ Dr Grant Henderson, who joined us at the event to discuss “accelerating mRNA and LNP manufacturing with platform analytical and process technologies”. The Vernal team also shared two posters in our poster zone; links to these can be found below. Dr Henderson is Vernal’s Senior Director of Commercial and Technical Operations and has recently shifted into this role to help researchers accelerate their journey from lead identification through candidate selection, and on to IND and commercial supply.
Accelerating manufacturing
We asked Dr Henderson for an insight into the content his session on accelerating mRNA and LNP manufacturing, and he emphasises that the team has “gone out of our way” to develop a seamless mRNA platform that reaches as far back as the research stage of an asset.
“Customers can come to us, we’ll give them research grade material, and from there it just develops all the way through; we can support them through their clinical manufacture and commercial.”
Talking technology
Our next question considers the technology or strategy that Vernal is using in its goal of “making mRNA readily available“.
“The technology is versatile, so it’s a platform that takes us all the way through from the strain development up to the LNP formulation.”
This can be done across a broad range of manufacturing scales with two different quality standards: the first offer for research grade (RUO) uses “open processing type equipment with reusable parts” , while the CGMP offering uses “fully single use” equipment, operating in a CGMP space.
Unmet need or fierce competition?
We next asked Dr Henderson about the company’s profile; is it meeting an unmet need or distinguishing itself from many competitors? He suggests that it’s “yes to both”!
“We look at it more of as an unmet need.”
Dr Henderson explains that his team helps early-stage companies solve hard problems around mRNA and LNP supply, including scale, and process and analytical development. With more mature companies, Vernal is able to accept all or the most robust aspects of their process and analytical technology and make improvements around the edges. They don’t expect customers to compromise on quality, regardless of their stage of research and development.
Dr Henderson identifies a lack of options to “get your product all the way through to commercial” or Phase I clinical manufacturing without partnering with a larger company. Vernal works with companies with “really exciting technology”, designed to accelerate the path to life-changing medicines, who need a purpose-built CDMO to deliver high purity, research grade and CGMP, drug substance, drug product, and intermediates.
Why WVC?
Finally, we cover the reasons for Vernal’s presence at the Congress. Dr Henderson comments on the “diverse set of exhibitors”, comprising both potential customers and competitors.
“Really it’s the entire cross-section of the market that Vernal is in.”
Vernal’s posters at WVC
Vernal also presented two posters during the Congress – click the links below to learn more!
Novel plasmid DNA-encoded poly(A) tails for mRNA synthesis: this study evaluates the stability of variant poly(A) regions, which are essential for the translation and stability of mRNA, and evaluates the biological activity of the mRNA containing the variant poly(A) tails.
mRNA capping technologies – effects on quality attributes, biological effects, and innate immune stimulation: this study compares two important mRNA capping technologies by evaluating mRNA integrity, percent Cap1 content, dsRNA content, in vivo expression, and innate immune activation in mice.
It was great to meet Dr Henderson and we hope that you enjoy the conversation.
For more conversations with our experts from the Congress in April do make sure you subscribe for weekly updates here!
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