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 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 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 | Jul 11, 2024 | Technology |
Seattle-based biotech Orlance announced in July 2024 that it has been awarded a Phase I Small Business Innovation Research (SBIR) grant from the US NIH to develop and optimise RNA vaccine formulations with its needle-free MACH-1 platform. The technology is intended to enhance the safety, stability, and efficacy of RNA vaccines for infectious diseases and cancer immunotherapy applications. MACH-1 is described as a “potentially significant advancement” in RNA vaccine delivery.
Meet MACH-1
MACH-1 is a needle-free vaccine platform that provides a “rapidly deployable, ambient stable, dose sparing, and easy to use product”. Orlance hopes it will increase immunisation in underserved regions by overcoming logistics or personnel difficulties and needlestick hesitancy. With pressurised gas, MACH-1 accelerates microparticles of DNA vaccines, RNA vaccines, or a combination. Vaccine microparticles penetrate the outer layer of skin to reach the epidermal layer, achieving intracellular delivery and transfection in local antigen presenting cells within the epidermis. This results in “robust” induction of systemic and mucosal antibody and cytotoxic T cell responses.
Compared to traditional lipid nanoparticle (LNP) RNA formulations, the MACH-1 platform uses dry, stable RNA-coated gold microparticles. It is needle-free and painless and ensures better stability at ambient temperatures with “significant supply chain advantages”.
Gene Gun project
The SBIR-funded project, “Gene Gun-delivered RNA vaccines”, is to be led by Orlance Principal Investigators Dr Hannah Frizzell and Dr Kenneth Bagley. They will aim to optimise RNA formulations for MACH-1 gene gun delivery to “maximise loading, maintain functional integrity, and ensure stability and immunogenicity”. The researchers will compare the effectiveness of MACH-1 delivered RNA vaccines against traditional LNP/RNA vaccines.
The 2-year grant provides $300,000 a year to enable Orlance to conduct preclinical studies, expected to “pave the way” for subsequent phases of development. Orlance has already received $13 million in SBIR funding, advancing MACH-1 towards readiness for initial regulatory filings in 2024. The company plans to initiate Phase I clinical trials for its lead infectious disease asset in 2025.
Kristyn Aalto, co-founder and CEO of Orlance, stated that the “breakthrough” of mRNA vaccines in recent years has “established the enormous potential of genetic (RNA and DNA vaccines”. However, there is still “significant work to do to improve utility and overall global health impact”.
“We are very grateful for NIH’s continued support and are rapidly accomplishing MACH-1 platform goals that could truly enhance the clinical research and impact of genetic vaccines.”
With a “well-developed” candidate portfolio and offerings across both DNA and RNA, Aalto hopes to “leverage the attributes of both platforms to provide ideal solutions tuned to the immunogenicity, protection, and durability profiles sought for specific indications”.
To hear the latest on innovative vaccine delivery approaches, why not join us in Barcelona for the Congress this October, or subscribe to our weekly newsletters here?
by Charlotte Kilpatrick | May 21, 2024 | Technology |
A study in npj vaccines in May 2024 presents a “promising” replicating RNA vaccine in a rhesus macaque model of Crimean-Congo haemorrhagic fever virus (CCHFV). The tick-borne febrile illness has expanded geographically, which places an “increasing number of people” at risk of CCHFV infection. As there are “no widely available vaccines” and a treatment with “unclear efficacy”, there is a clear unmet need. The authors present their model as an alternative to the established cynomolgus macaque model and find that their vaccine is “immunogenic and protective in non-human primates after prime-boost immunisation”.
CCHF
The authors state that Crimean-Congo haemorrhagic fever, caused by CCHFV, can cause “severe haemorrhagic disease in infected humans”, beginning as a non-specific fever, myalgia, nausea, diarrhoea, and general malaise. This can “rapidly progress” and in some regions, case fatality rates can be as high as 30-40%. The current, widely-used therapy is ribavirin, but efficacy in both human and animal models is “conflicting and suggestive of poor efficacy” when administered later in infection.
While there is an inactivated preparation of CCHFV grown in mouse brains used as a vaccine in Bulgaria, there are no approved vaccines for CCHF. Thus, prevention is limited to “control of exposure”.
Research to date
Previous research evaluated a replicating RNA (repRNA) vaccine for CCHFV in a lethal mouse challenge model. The vaccine is based on an alphavirus replicon system, in which the structural proteins of the Venezuelan equine encephalitis virus are replaced with a gene-of-interest, resulting in RNA that can self-amplify. This leads to dose sparing and mimics an authentic viral infection without the ability to spread from the initially transfected cell.
The paper states that delivery of the repRNA is achieved by complexing the RNA with a cationic nanocarrier called LION with several features:
- May induce less systemic inflammation than current lipid nanoparticles
- Has been manufactured under current good manufacturing practices
- Has demonstrated safety and immunogenicity in humans
- Is the basis for a product that achieved emergency use authorisation in India
Research has established a non-human primate (NHP) model of CCHF in cynomolgus macaques. The latest paper presents an alternative model; the passaged strain of CCHFV causes viraemia and mild disease “consistently” in rhesus macaques.
Supportive data
The data demonstrate the protective efficacy of a repRNA vaccine for CCHFV in RM, with this model providing a “viable alternative model”. In the study, CCHFV-specific antibodies “significantly and inversely” correlated with viral loads in multiple tissues, including key tissues like liver, kidney, heart, and lung tissue.
“All animals developed a CCHFV-specific response following vaccination, demonstrating that our repRNA platform is immunogenic in RM.”
In both current and previous research, nucleoprotein (NP)-specific antibodies “appear to be the major correlate of protection”. While the CM vaccinated with DNA-expressed NP alone were protected from CCHFV challenge, the repRNA vaccine “may provide quicker immunity” than that approach. Furthermore, CCHFV-specific humoral immunity was observed “after a single immunisation”, but boosting may “still be warranted to confer optimal immunity”.
“Cumulatively, our data support the continued development of this vaccine for CCHFV.”
For more on innovative approaches to infectious disease, why not subscribe to our weekly newsletters here?
by Charlotte Kilpatrick | May 15, 2024 | Technology |
At The World Vaccine Congress in Washington VaccineNation conducted a series of conversations with some of our experts. In this interview we meet BARDA’s Dr Kumiko Lippold, who joined us to share some very exciting news about Patch Forward Prize and what the team is looking for! Dr Lippold is a health scientist at BARDA, wearing “many different hats”! One such hat is Acting Branch Chief of the Alliance Office at DRIVe. Additionally, she is the programme manager for the prize that we discuss. It was great to speak to Dr Lippold; we hope that you enjoy the conversation and possibly get the encouragement to put yourself or your team forward!
The Patch Forward Prize
During the Congress Dr Lippold and team were sharing information about the newly launched “Patch Forward Prize“, with a prize purse of $50 million! We asked her to share a bit of insight into this initiative. She helpfully puts BARDA’s approach into context, with the mission of “advancing health security” and establish “really unique public private partnerships”. This means closely partnering with industry to “enhance our preparedness and response posture”.
“The Patch Forward Prize is one example of an innovative effort that we have within BARDA to help enhance our preparedness and response.”
It seeks to advance the development of a microneedle-based RNA vaccine.
“Ultimately our goal with this effort is to see a microneedle-based vaccine, either for COVID-19, seasonal flu, or pandemic influenza, which has become quite timely with the H5N1 emergence, and see that be formulated onto a microneedle patch that can ultimately be commercialised and reach the market where people can use it.”
This effort falls under Project NextGen to focus on “improving access to highly effective medical countermeasures”.
Meeting a need
As Dr Lippold mentions enhancing preparedness, we asked about the needs within this that the prize might be addressing. She identifies a “couple of different goals”. The first is the “promise” of microneedle patches as a “tool in our preparedness and response toolbox”.
“Microneedle patches are not necessarily the sole solution from that perspective, they are one component of a holistic, well-rounded response effort.”
Benefits from microneedle patches include increased thermostability and reduced reliance on cold-chain systems. Another goal is to “help support the development of both early-stage developers and advanced developers”. Companies are at “various stages of development”. Thus, the prize has been designed deliberately to ensure interests are balanced and the field is raised.
“In terms of the things that we’re trying to reach, and we’re trying to solicit as part of this, we’re trying to help facilitate the development of new impactful partnerships, the things that are at the heart of what BARDA aims to do…so that we can help mature these microneedle patches.”
Getting involved
We then asked Dr Lippold what a successful or ideal application might involve, to shed some light or provide some hints for anyone who is interested!
“The real strength of a prize challenge is that it allows us to put a really ambitious goal, and be a little agnostic to the solution.”
While BARDA has “typically” operated with contracts, the prize challenge is a new way of identifying and encouraging innovation.
“We are putting out the goal of ‘formulate an RNA vaccine onto a patch’ – how you get there, as long as you meet our eligibility criteria, we are agnostic to.”
Dr Lippold is looking for “as many different innovative approaches as we possibly can” with “technically sound” approaches that will be translated forward. However, the prize has a three-stage approach: a concept stage, a preclinical stage, and a Phase I clinical stage. Do head to the website to see where you might fit in here!
“We don’t want to define success because success might come in a package that we didn’t anticipate.”
Why WVC?
As usual, we conclude with a question about the event. Dr Lippold shares that the chance to connect with companies is a “really incredible opportunity”.
“BARDA is here to learn from companies, to meet you where you’re at…we always try to keep our door open.”
It was lovely to meet Dr Lippold at the Congress and to be able to get some insights into this fantastic opportunity; don’t forget to check out the website for more information.
For more conversations with our experts from the Congress in April do make sure you subscribe for weekly updates here!
by Charlotte Kilpatrick | May 1, 2024 | Technology |
A PNAS study shared by researchers at UC Riverside in April 2024 explores the benefits of a “one-and-done” approach to vaccinations for infectious diseases. The paper characterises a “unique live-attenuated RNA virus vaccine”, in which attenuation resulted from the elimination of the viral RNAi suppressor and enhanced the production of virus-targeting small-interfering RNAs. The researchers identify “potential for developing a distinct type of virus vaccine” to provide “rapid and effective protection” in “infants and other immune-compromised individuals”.
Investigating the vaccine
In the paper the authors present their investigations into the protective antiviral immunity induced in mice through immunisation with NoVΔB2. NoVΔB2 is a live-attenuated, VSR-disabled RNA virus vaccine. Previous studies have “extensively characterised” its RNA-based virus-specific antiviral responses. In this study, mice “produce highly abundant NoV (Nodamura virus)-specific vsiRNAs that are readily detectable”. These vsiRNAs have a role as the “specificity-determinants of the induced antiviral immunity”. Mice who had been immunised with NoVΔB2 also “specifically” suppressed the accumulation of a recombinant Sindbus virus carrying a NoV RNA sequence.
“Our findings from this work show that the protective antiviral immunity induced by a single shot with live NoVΔB2 is both virus-specific and long-lasting, which are the same as those virus vaccines that activate the adaptive immunity.”
However, the protective immunity induced in this study reveals “several distinct features”. After immunisation, neonatal BALB/c and Rag1−/− mice became “fully protected” against lethal NoV challenge and exhibited “no signs of diseases”. Furthermore, NoV accumulation was “undetectable in most or all” neonatal BALB/c and Rag1−/− mice following NoV inoculation. This reveals “efficient inhibition of the challenge infection” in newborn mice due to the induced antiviral responses”.
The results also indicate that the adaptive immunity mediated by B and T lymphocytes is “dispensable for the protective immunity activated by immunisation with the live-attenuated VSR-disabled NoVΔB2.”
“These distinct features of NoVΔB2-induced protection align with the earlier conclusion that enhanced production of the circulating and stably maintained virus-targeting vsiRNAs confers antiviral protection by the RNAi pathway in mice immunised with the live-attenuated VSR-disabled virus vaccine.”
Broad protection and other applications
A statement from UC Riverside considers the risks associated with predicting and targeting viral strains. This is exemplified in annual flu vaccine efforts.
“People line up to get their updated vaccine, hoping the researchers formulated the shot correctly.”
However, the latest evidence suggests that targeting a “common” part of the viral genome could “eliminate the need to create all these different shots”. Dr Rong Hai, one of the authors of the paper, emphasises that the strategy is “broad”.
“It is broadly applicable to any number of viruses, broadly effective against any variant of a virus, and safe for a broad spectrum of people. This could be the universal vaccine that we have been looking for.”
Distinguished professor of microbiology and lead paper author is Dr Shou-wei Ding, who is seeking to “weaken the virus” so that it “loses the battle to the host RNAi response”.
“A virus weakened in this way can be used as a vaccine for boosting our RNAi immune system.”
This research has particularly positive implications for infants, who would “no longer have to depend on their mothers’ antibodies” and could be used for “several well-known human pathogens” such as dengue and SARS.
“This should be applicable to these viruses in an easy transfer of knowledge.”
For the latest vaccine technology research and development, don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Mar 26, 2024 | Technology |
In March 2024 Altamira Therapeutics announced that it has entered a collaboration with Univercells to evaluate the use of its SemaPhore platform to deliver mRNA vaccines. The agreement ensures that Univercells will test a proprietary mRNA vaccine delivered with SemaPhore nanoparticle platform in vitro and in vivo. If these prove successful, the companies will discuss and negotiate a commercial agreement for the development and manufacturing of nanoparticle-based mRNA vaccines through Univercells’ production platform.
SemaPhore
Altamira’s SemaPhore platform is “versatile” and designed to “enable safe and effective delivery of mRNA into target cells” through systemic or local administration. It is based on a proprietary 21 amino acid peptide that can engage “any type” of RNA in rapid self-assembly into a polyplex, which has a size, charge, and other physical features. These allow it to escape hepatic clearance to reach target tissues other than the liver.
“SemaPhore protects the RNA payload from degradation in the circulation and allows for rapid and effective cell entrance. Efficient delivery and positive treatment outcomes have been demonstrated in multiple murine models of disease so far.”
Dr Covadonga Pañeda, Altamira’s Chief Operating Officer, is “thrilled to initiate this collaboration”.
“SemaPhore has shown to be an efficient delivery vehicle for therapeutic RNA in many different disease models. With this collaboration we will explore for the first time its potential utility in delivery mRNA vaccines.”
Dr Pañeda highlights that current delivery vehicles that are used in the field “suffer from significant rates of mRNA loss during cell entrance”. Furthermore, they can cause “local or systemic side effects”.
“SemaPhore reduces mRNA loss during cell entrance, which may allow for using lower doses. This feature, together with its favourable tolerability profile could make SemaPhore a compelling alternative to conventional delivery vehicles.”
Chief Technology Officer of Univercells is Dr José Castillo who is “delighted to be partnering with Altamira to explore better ways to deliver mRNA to patients”.
“mRNA vaccines, and mRNA in general, have proven to be a game-changer in how we prevent, treat, and cure diseases in a range of fields from oncology to infectious diseases. To unlock its full potential, however, we need constant innovation to make mRNA products more effective, efficient, and affordable. One key step is to develop platforms that use lower doses.”
For all things RNA and innovation, why not join us at the Congress in Washington this April to attend the RNA workshop and more, or subscribe to our newsletters here?
by Charlotte Kilpatrick | Mar 7, 2024 | Technology |
CEPI announced in March 2024 that it is providing up to $1 million funding to researchers at Amplitude Therapeutics in the US to support preclinical studies to assess the potential benefits of their trans-amplifying mRNA vaccine approach. This partnership comes under CEPI’s call for innovations to support the 100 Days Mission for pandemic preparedness.
A new approach
While “conventional” mRNA vaccines found fame during the COVID-19 pandemic as safe and effective ways to save lives, self-amplifying mRNA designs are also becoming “more prominent”. Self-amplifying mRNA vaccines are “more specialised”, containing genetic instructions for the antigen and replicase, an enzyme that “serves as a built-in photocopier” to teach the body to replicate mRNA. This design present “important advantages” over “conventional mRNA vaccines”, such as the possible reduction of a dose. However, there are limitations. As the additional genetic instructions make the vaccine sequence “at least three times longer” than standard mRNA vaccine sequences, manufacturing and delivery challenges can arise.
Trans-amplifying mRNA vaccines comprise two separate, shorter RNA fragments: one encodes the antigen, and one encodes the replicase. This separation could facilitate easier production and mean up to 100 times less antigen-encoded RNA required per dose. Furthermore, the replicase enzyme can be produced before an outbreak.
From one pandemic to another
Dr In-Kyu Yoon, Acting Executive Director of Vaccine R&D at CEPI identifies “many exciting technologies” coming out of the COVID-19 pandemic.
“We must investigate whether they fit the bill of developing vaccines against future viral threats within a 100-day timeline. We already know mRNA is fast and flexible, and now new techniques like trans-amplifying mRNA vaccine technologies may further enhance its offering by significantly extending antigen supply while also allowing for key components of the vaccine to be made ahead of time.”
Dr Cory Sago, CEO of Amplitude Therapeutics is “grateful” for CEPI’s support as the team works to “advance trans-amplifying RNA vaccines for pandemic preparedness”.
“Our data suggest that trans-amplifying RNA may have some distinct advantages over existing mRNA technologies, including improved expression and flexibility of manufacturing.”
To hear more on the revolutionary platforms and technologies the vaccine community is exploring to improve pandemic preparedness why not join us at the Congress in Washington this April by getting your tickets here? If you can’t make it, don’t forget to subscribe here.
by Charlotte Kilpatrick | Feb 14, 2024 | Technology |
In February 2024 Replicate Bioscience announced “positive” results from a Phase I trial of the comapny’s self-replicating RNA (srRNA)-based rabies vaccine, RBI-4000. The trial evaluated the safety and immunogenicity of the vaccine with participants receiving one or two low doses. Replicate reports that “at all assessed doses” (0.1 mcg, 1mcg, or 10 mcg), the vaccine achieved a “strong immune response” with protective virus-neutralising antibody titers above the WHO-defined immune surrogate level of protection against the virus. Furthermore, the RBI-4000 was “well tolerated” at all dose levels.
RBI-4000
“A next-generation rabies vaccine with improved immunogenicity and simpler manufacturing represents an opportunity to broaden access to rabies prevention worldwide.”
The first vaccine candidate from Replicate is RBI-4000, an srRNA vaccine developed to “stimulate virus-neutralising immune responses to rabies for prophylactic use”. The srRNA platform amplifies protein expression with self-limited replication unlocking “new opportunities” for more patients across a broad range of disease.
What do the data show?
Replicate states that the data indicate:
- The surrogate metric of protection was achieved in most subjects in the ultra-low 0.1 mcg cohort – the lowest dose of any RNA technology reported to achieve surrogate of protection in humans
- Single administration met the surrogate metric of protection for most subjects in multiple cohorts
- Favourable tolerability across all dose levels tested, with no severe adverse events
- Superior therapeutic index with clinical bioactivity and tolerability at all doses tested
Exceptional results
Dr Nathaniel Wang, CEO of Replicate, commented that the results “have exceeded our expectations” and show the “power and potential” of the technology, de-risking the platform, process, and pipeline.
“Achieving a broad therapeutic window is an important step-up from other existing mRNA and srRNA approaches, which allows us to expand applications of our self-replicating RNA to complex infectious diseases, off-the-shelf cancer vaccines, and as a platform for protein production.”
Dr Michael Ehlers, co-Founder and Board Chair of Replicate suggested that “when we founded Replicate, we envisioned a class of RNA therapeutics capable of treating many more diseases and reaching many more patients”.
“These data represent exciting progress towards realising that vision.”
We look forward to hearing more from Replicate at the Congress in Washington during our RNA workshop. Do join us by getting your tickets here and don’t forget to subscribe to our weekly newsletters!
by Charlotte Kilpatrick | Jan 26, 2024 | Technology |
In January 2024 CEPI announced that it is “teaming up with leading scientists” at the Houston Methodist Research Institute (HMRI) to develop a “promising” kind of technology that it hopes could “pave the way for new ‘circular RNA’ vaccines”, which would be “more stable, durable, and cost-effective”. CEPI is contributing funding of up to $3.8 million to the Houston Methodist vaccinology team in support of its ‘circRNA’ platform. This offers “significant potential beyond mRNA vaccines”. The project will focus on designing and evaluating candidates against chikungunya, one of CEPI’s priority pathogens, aiming to generate preclinical proof of concept for the platform.
RNA benefits and limitations
Although mRNA vaccines are “expected to play a crucial role” in disease prevention and control, they are limited. For example, the potential provocation of local reactions or short-term fever in people who take them could be a barrier to uptake.
“Relative to other types of vaccine, they are currently expensive to manufacture and require costly and complex cold-chain storage and transportation infrastructure.”
Enter circular RNA. This uses closed-loop RNA, which might enable candidates to be more stable and durable than linear-based mRNA vaccines. It could also deliver “improved efficacy in smaller doses”. Although HMRI’s circRNA platform is “still in the early stages of development”, CEPI has identified potential for effectiveness in single-dose regimens, which reduces the amount of RNA required for each dose and lowers the cost of RNA-based vaccines. This would contribute to greater accessibility.
“Molecular junk” to vaccine hero
Dr In-Kyu-Yoon, Acting Director of Vaccine R&D at CEPI explains that circular RNA was previously considered “molecular junk”. However, research research has indicated that it could be “harnessed” for RNA-based medicines.
“If effective, these circRNA vaccines could progress this new scientific era of mRNA vaccinology even further, leveraging not only the speed at which the technology can be designed and tested in response to infectious disease outbreaks but also the potential to create more durable and accessible mRNA vaccines for greater global protection when faced with a deadly disease threat.”
Dr H. Dirk Sostman, President and CEO of the Houston Methodist Academic Institute, is “excited to be working with CEPI” in this effort to “protect the world against emerging viral threats”.
“Houston Methodist is leading medicine by generating fundamental scientific insights that have transformational effects on human health.”
If you’re interested in participating in discussions on the contributions that RNA can make to global health, why not join us in Washington for the RNA workshop this April? If you can’t make that, do subscribe for regular vaccine insights!
