DUBLIN – Bavarian Nordic A/S, Europe’s largest independent vaccine developer, is placing a bet on virus-like particle (VLP) technology as a potentially useful contribution to the desperate global effort to push back against SARS-CoV-2. The Copenhagen, Denmark-based firm is entering an agreement with fellow Danish firm, Hørsholm-based Adaptvac ApS, to take forward the latter’s VLP-based SARS-CoV-2 subunit vaccine. The partners hope to move into clinical trials later this year and to deliver preliminary data early in 2021.
The companies plan to finalize a formal license agreement in the coming months, but Bavarian Nordic’s disclosure on May 6 sends a significant message to the market, given the relatively low profile of Adaptvac until now. “Obviously we’ve been looking at and thinking about what we should do,” Bavarian Nordic CEO Paul Chaplin told BioWorld. “We’re almost obligated to get involved.”
Bavarian Nordic is best known for its development of a smallpox vaccine, Jynneos (smallpox and monkeypox vaccine, live, non-replicating), which gained FDA approval last September, having previously secured approvals in Europe and Canada. It employs Bavarian’s modified vaccinia Ankara (MVA) strain, an attenuated, non-replicating orthopoxvirus. The same construct can be genetically modified with the addition of recombinant viral antigens to elicit immune responses against non-poxviruses.
A heterologous prime-boost vaccine against Ebola virus, which Johnson & Johnson, of New Brunswick, N.J., has developed in collaboration with Bavarian, is one such example. Its comprises Ad26.ZEBOV, which is based on J&J’s Advac adenovirus vector and Per.C6 protein expression system, and Bavarian’s MVA-BN-Filo, which expresses Ebola glycoproteins, as well as proteins from other filoviruses. It is currently under regulatory review in Europe and approval is currently expected around mid-2020.
For COVID-19, however, Bavarian has taken the view that MVA is not suitable, based on criteria published by the World Health Organization, chief among them being the need for a single-shot vaccine capable of eliciting a protective immune response in two weeks. VLP may offer a better bet. “I believe it can meet the criterion of a one-shot vaccine,” Chaplin said. Its manufacturing requirements are also favorable – it can be produced in highly scalable E. coli expression system. MVA, in contrast, relies on a more cumbersome egg-based production process. “All in all, we think this has a really good chance of meeting the criteria,” he said.
Not all of those vaccines currently in development will. “A lot of the technologies going into the clinic we know don’t work in the elderly,” Chaplin said. “Adenovirus can’t always do it on its own,” he added. “Adenoviruses are very immunogenic but don’t induce a long-lived immune response.” J&J is staying loyal to its Advac vector and Per.C6 platforms – which it gained through its acquisition of Crucell in 2011 – and has enlisted the help of Emergent Biosolutions Inc., of Gaithersburg, Md., to support its goal of producing a billion doses. Development of a recombinant adenovirus-based vaccine is also underway in China.
RNA-based vaccines have been quick out of the block – and first into clinical trials – but the technology is still unproven, Chaplin said, adding that clinical data from other settings “doesn’t look that compelling.” Clinical data from the many COVID-19 vaccine trials that are either planned or already underway will, of course, be the ultimate arbiter of success. “I’m sure there’ll be multiple vaccines for COVID-19 – and there will need to be,” Chaplin said.
The basic VLP concept is decades old. Its most successful application is in Merck & Co. Inc.’s human papillomavirus (HPV) vaccine Gardasil (human papillomavirus quadrivalent (types 6, 11, 16 and 18) vaccine, recombinant) and its successor product, Gardasil 9 (human papillomavirus 9-valent vaccine, recombinant), which employ VLPs assembled from the L1 major capsid protein of four and nine different HPV serotypes, respectively.
The technology that Bavarian Nordic is backing is still preclinical. Adaptvac was formed in 2017 as a joint venture between Expres2ion Biotech Holding AB, which has developed an insect-cell-based protein expression system, and Nextgen Vaccines ApS, a University of Copenhagen spin-out and VLP technology developer. Its lead program is in cancer rather than infectious disease – it consists of a VLP-based therapeutic vaccine directed against HER2/Neu cancers. The construct is based on a capsid protein produced by bacteriophage AP205, which ordinarily infects enteric Acinetobacter bacteria. Adaptvac’s AP205-based VLP can be readily programmed in a plug-and-play fashion to carry any recombinant antigen of interest, as the latter proteins are not embedded in the VLP structure but are attached to it using the Spytag/Spycatcher protein conjugation system.
Adaptvac and Expres2ion are both members of a European Commission-funded consortium that has already begun work on the VLP-based SARS-CoV2 vaccine, in collaboration with academic researchers from the Leiden University Medical Center, in the Netherlands, the Institute for Tropical Medicine at the University of Tübingen, Germany, the Department of Immunology and Microbiology at the University of Copenhagen, and the Laboratory of Virology at Wageningen University in the Netherlands. That group includes scientists with preclinical and clinical experience of working with other coronaviruses, including SARS and MERS. The €2.7 million (US$2.9 million) grant it received will fund initial development efforts, but Bavarian Nordic will need to raise additional resources for large-scale trials. Positive progress at eliciting neutralizing antibodies against SARS-CoV-2 would readily elicit more funding.
Several other VLP-based COVID-19 vaccine development programs are underway at Medicago, a subsidiary of Osaka-based Mitsubishi Tanabe Pharma, at Bristol, U.K.-based Imophoron Ltd., and at New-York-based Ibio Inc.
Shares in Bavarian Nordic (Copenhagen:BAVA) closed May 6 at DKK166.40 (US$24.11), a gain of 2.5%. Shares in Expres2ion (Stockholm:EXPRS2) gained 6.6% to close at SEK18.50 (US$1.88).