Durability and Cross-Reactivity of Immune Responses Induced by an AS03-Adjuvanted Plant-Based Recombinant Virus-Like Particle Vaccine for COVID-19

As the SARS-COV-2 pandemic evolves, what is expected of vaccines extends beyond efficacy to include consideration of both durability and variant cross-reactivity. This report expands on previously reported immunogenicity results from a Phase 1 trial of an AS03-adjuvanted, plant-based coronavirus-like particle (CoVLP) displaying the spike (S) glycoprotein of the ancestral SARS-CoV-2 virus in healthy adults 18-49 years of age ([NCT04450004][1]). When humoral and cellular responses against the ancestral strain were evaluated 6 months post-second dose (D201), 100% of vaccinated individuals retained binding antibodies, and ∼95% retained neutralizing antibodies; interferon gamma (IFN-γ) and interleukin 4 (IL-4) responses directed against the ancestral S protein were also still detectable in ∼94% and ∼92% of vaccinees respectively. Variant-specific, cross-reactive neutralizing antibody (NAb) levels were assessed at D42 and D201 using both live wild-type and pseudovirion assays (Alpha, Beta, Gamma) or the wild-type assay alone (Delta, Omicron). In the wild-type assay, broad cross-reactivity was detected against all variants at D42 (100% Alpha and Delta, 94% Beta and Gamma, 74% Omicron). At D201, cross-reactive antibodies were detectable in almost all participants against Alpha, Gamma and Delta variants (94%) and the Beta variant (83%) and in a smaller proportion against Omicron (44%). Results were similar in the pseudovirion assay (D42, 100% cross-reactivity to Alpha and Gamma variants, 95% to Beta variant, D201, 94% for Alpha, Beta and Gamma variants). These data suggest that two doses of 3.75 µg CoVLP+AS03 elicit a durable and cross-reactive response that persists for at least 6 months post-vaccination. ### Competing Interest Statement P. Gobeil, I. Boulay, N. Charland, A. Lorin, S. Pillet, B. Ward, M-A D′Aoust, and N. Landry are or were either employees of Medicago Inc. or received salary support from Medicago Inc. P. Boutet, F. Roman, R. Van Der Most, and M.A. Ceregido are or were employees of GlaxoSmithKline and hold restricted shares in the GSK group of companies. ### Clinical Trial NCT04450004 ### Funding Statement The study was sponsored by Medicago Inc. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approved was provided by the Advarra Institutional Review Board as well as the Health Products and Food Branch of Health Canada and the study was carried out in accordance with the Declaration of Helsinki and the principles of Good Clinical Practices. Participants were recruited from existing databases of volunteers, and written informed consent was obtained from all study participants before any study procedure. Participants were offered modest compensation for their participation in this study (that is, time off work and displacement costs). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Medicago Inc. is committed to providing access to anonymized data collected during the trial that underlie the results reported in this article, at the end of the clinical trial, which is currently scheduled to be 1 year after the last participant is enrolled, unless granted an extension. Medicago Inc. will collaborate with its partners (GlaxoSmithKline, Rixensart, Belgium) on such requests before disclosure. Proposals should be directed to wardb{at}medicago.com or daoustma{at}medicago.com. To gain access, data requestors will need to sign a data access agreement and access will be granted for non-commercial research purposes only. [1]: https://clinicaltrials.gov/ct2/show/NCT04450004