Vicebio and its molecular clamp vaccine raise big to tackle respiratory viruses

Today, Vicebio, a UK-based vaccine company completed a $100 million series B round led by TCGX with investments from Goldman Sachs Alternatives, Avoro Ventures, venBio, and participation from UniQuest and founding investor Medicxi. With its molecular clamp technology and its lead multivalent vaccine candidate targeting both respiratory syncytial virus (RSV) and human metapneumovirus (hMPV), Vicebio aims to solve unmet medical needs in some of the most vulnerable populations.

The COVID-19 episode raised awareness about respiratory viruses and the global focus has shifted to developing vaccines that can protect against multiple respiratory pathogens, especially for at-risk groups like the elderly and immunocompromised. Multivalent vaccines, which protect against more than one pathogen, are becoming a promising solution to this challenge.

Recent years have seen a significant increase in investment in respiratory virus vaccine development, with multivalent approaches taking center stage. The global market for respiratory vaccines is projected to reach nearly $70 billion in 2024, driven by the rising prevalence of respiratory diseases, increased public health initiatives, and technological advancements in vaccine platforms.

What is the particularity of Vicebio’s molecular clamp technology and how does it compare to the broader respiratory virus landscape?

How does the molecular clamp technology work?

Molecular clamp technology is a vaccine platform designed to stabilize viral surface proteins in their prefusion state, which is the form they take before they infect cells. Emmanuel Hannon, chief executive officer (CEO) of Vicebio explained how the technology works.

“Vicebio’s journey began with a key observation – it is possible to stabilize a highly important antigenic target for pathogenic viruses. The technology stabilizes viral glycoproteins in their highly immunogenic ‘prefusion’ conformation, which is crucial for eliciting strong protective immune responses. This approach enables the production of highly effective candidate vaccines that are easy to manufacture and can be distributed in ready-to-use prefilled syringes. The molecular clamp technology is applicable to a wide range of viruses, including RSV, hMPV, parainfluenza and influenza viruses, and coronaviruses”

This prefusion form triggers a stronger immune response than the postfusion state. The core of the technology involves attaching a molecular “clamp” to viral glycoproteins, preventing them from shifting into their postfusion form. This innovation stems from research at the University of Queensland, where scientists developed a method to ensure that these viral proteins retain the structure that the immune system is best able to recognize and fight​.

Molecular clamp technology differs from other vaccine platforms like mRNA or viral vector vaccines in how it delivers antigens. While mRNA vaccines instruct the body’s cells to produce viral proteins, molecular clamp vaccines directly present stabilized viral proteins to the immune system, allowing for a more controlled and direct immune response. This is particularly useful for viruses like RSV and hMPV, which have complex surface proteins that require stabilization to maintain their immunogenicity.

For instance, mRNA vaccines depend on the body’s ability to produce proteins based on genetic instructions, which introduces variability in how individuals respond to the vaccine. By contrast, molecular clamp vaccines bypass this step by delivering proteins in their most immunogenic form, making them potentially more consistent across populations​.

Respiratory viruses like RSV and hMPV are notoriously difficult to develop vaccines for, in part because their surface proteins change shape when transitioning between the prefusion and postfusion forms. These structural shifts can make it harder for vaccines to induce a strong immune response. The prefusion state is particularly effective at stimulating the production of neutralizing antibodies, which are key to long-lasting immunity.

Vicebio’s path: Lesson learned from past failures of the molecular clamp?

Vicebio is not the first company to use molecular clamp technology, and there has been a notable setback with its previous use. This occurred during the early stages of the COVID-19 pandemic when the University of Queensland (UQ), in collaboration with CSL, developed a COVID-19 vaccine candidate using this technology. The vaccine showed promising results in terms of safety and immune response, but it was abandoned after participants in early trials produced false-positive human immunodeficiency virus (HIV) test results.

“The first-generation molecular clamp technology has already been applied to generate vaccine candidates against several life-threatening respiratory viruses including SARSCoV-2. The first-generation molecular clamp was based on a subdomain of gp41 from HIV, which led to an unintended consequence in human vaccine trials: some individuals developed antibodies that cross-reacted with HIV, causing false-positive results in HIV diagnostic tests. This posed a significant challenge for its use in human vaccines,” explained Hannon.

The decision to discontinue the UQ vaccine was based on the fear that these false-positive HIV tests could undermine public confidence in the vaccine, despite the fact that there was no actual risk of HIV infection. UQ’s scientists highlighted that while the vaccine could have been re-engineered to avoid this issue, the process would have caused significant delays. At the time, with the urgent need for a COVID-19 vaccine, the decision was made to abandon the candidate​.

“In response, Vicebio developed a second-generation molecular clamp sequence that addresses this issue. This new version eliminates any false reactivity signals in HIV tests, thereby avoiding the false seroconversion problems perceived with the first-generation sequence. The new version of the SARS-CoV-2 vaccine based on the second generation was shown to be highly competitive versus the Novavax vaccine in the booster human clinical trial last year,” said Hanon.

“Vicebio has now made significant progress on the development of three vaccine antigens: RSV, hMPV, and PIV3 viral antigens using the second-generation molecular clamp and Vicebio is now proceeding with a first-in-human clinical trial with a bivalent candidate vaccine targeting RSV and hMPV,” added the company’s CEO.

While molecular clamp as a concept isn’t widespread in current vaccine platforms, the idea of stabilizing viral proteins in their prefusion state has gained traction in other contexts. GSK and Pfizer, for instance, have used prefusion protein structures in their RSV vaccines, although they didn’t rely on the specific molecular clamp approach. These companies stabilized the F protein in RSV, which is critical for generating a strong immune response​.

Vicebio is now the only company still advancing this molecular clamp approach, and the next steps for the company are clear. “We expect interim analysis by mid-2025. If positive, these results will constitute a proof of concept in terms of safety and immunogenicity that the molecular clamp technology can be successfully applied beyond SARS-CoV2. We have already decided to progress at risk on the development of a trivalent vaccine for which the clinical trial will start a few months after the availability of the results of the first trial,” said Hanon.

The growing trend of multivalent vaccines

According to Hanon, there is still a long road ahead for respiratory virus treatment. “There is no broad use of therapeutic approach to address the medical need due to these respiratory viral infections and diseases. It has been shown that the most effective way to address these medical needs has been so far by prevention.”

However, Vicebio’s CEO notes that the landscape for vaccine development, particularly for respiratory viruses, is rapidly changing. “We’re already seeing a shift towards combining vaccines, as demonstrated by the development of influenza and SARS-CoV-2 combination vaccines, which are being rolled out in joint vaccination campaigns to improve coverage. However, RSV presents a unique challenge. Unlike flu and COVID-19, RSV vaccines are unlikely to drive annual revaccination, which makes their combination with influenza vaccines less probable.”

Multivalent vaccines are designed to protect against multiple pathogens or strains in a single dose. This approach is gaining momentum, particularly for respiratory viruses like RSV and hMPV, because of the growing need to cover multiple respiratory threats simultaneously. These viruses, along with others like parainfluenza and Influenza, place a significant burden on healthcare systems, particularly in vulnerable populations like the elderly and immunocompromised.

“The high unmet medical need drove the decision to develop a bivalent candidate vaccine for RSV-hMPV and to develop a trivalent candidate vaccine for RSV-hMPV-PIV3. RSV, hMPV, and PIV3 are linked to a significant burden of disease in susceptible populations composed of young children, older adults, elderly, and immunocompromised individuals. in these susceptible populations, it can lead not only to hospitalizations for severe acute low respiratory tract diseases (LRTD), but also might require mechanical ventilation and might lead to death,” said Hanon.

So, in the case of Vicebio, the decision to pursue a bivalent (VXB-241) and a trivalent (VXB-251) vaccine that targets both RSV and hMPV (and parainfluenza virus 3 in the case of VXB-251) reflects a strategic move to address two high-impact respiratory viruses in one shot. RSV and hMPV share similar transmission patterns and disproportionately affect the same vulnerable populations, making a combined vaccine particularly valuable for public health​.

Indeed, according to Hannon, when it comes to respiratory viruses, multivalency has an edge over monovalent vaccines. “Monovalent RSV vaccines face additional hurdles. They are not cost-effective enough to support broad recommendations, and they also pose practical challenges. They are not easy to use due to their multi-vial presentations, and their manufacturing process is more complicated, often requiring lyophilization. These factors point to a clear need for multivalent combination vaccines that are easier to use, manufacturable at large scale, and cost-effective.”

“Increasing the coverage of such vaccines by including additional viruses responsible for a significant burden of disease will have a highly favorable impact on the overall cost-effectiveness of such vaccines. This could lead to much more favorable recommendations and even to preferential ones,” Hanon added.

Multivalency in vaccines is not new but is becoming more sophisticated with recent technological advancements. Traditional multivalent vaccines, like the MMR (Measles, Mumps, Rubella) vaccine, have been a cornerstone of public health for decades. However, the recent push for multivalent respiratory vaccines is largely driven by the need to combat multiple respiratory viruses at once, which has been further emphasized by the COVID-19 pandemic​. For example, Moderna and GSK are also pursuing multivalent vaccines that target multiple respiratory pathogens, including combinations of RSV, flu, and COVID-19​.

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