Indeed, next-generation vaccine strategies need to address efficient protection for the unvaccinated and naïve population, such as young children at risk against future circulating VOC 12. Thus, there is an urgent unmet need for optimized variant-proof COVID-19 vaccines to provide broad and durable protection against existing and future variants.īecause of the continuous fast replacement of BA.1 by other Omicron sub-lineages (BA.2, BA.2.12.1, BA.4, BA.5, BQ.1, BQ.1.1 …) showing similar to higher immune escape and transmission rates than BA.1 6, 7, 8, 9, the current vaccine strategies chasing each new variants need to be re-evaluated, for booster doses as well as for primary immunization 10, 11. It is now well established that SARS-CoV-2 is endemic, with unpredictable severity 5. Although multiple vaccines have been approved for use in a record time, all the authorized vaccines were originally designed to target the ancestral D614 strain 3, 4. SARS-CoV-2 evolution continues at a higher speed than previously anticipated and is now mainly driven by immune escape as demonstrated by the high incidence of Omicron symptomatic disease in vaccinated individuals 2. Several VOC have been identified (Alpha, Beta, Gamma, Delta, and Omicron BA.1), along with highly diverse subvariants of Omicron, some of which have been classified as new VOC by the European Centre for Disease Prevention and Control (BA.4 and BA.5) 1.

However, the relative genetic stability ended after the first year when variants of concern (VOC) displaying multiple mutations in the Spike antigen, successively displaced the preceding strain causing multiple waves of infections worldwide.

During the first six months of the pandemic, a variant with a single mutation in the Spike antigen (D614G), replaced the circulating ancestral Wuhan strain (D614). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease (COVID-19), emerged in late 2019. Our findings demonstrate the potential of a Beta-containing bivalent CoV2 preS dTM-AS03 formulation to provide broad and durable immunogenicity, as well as protection against VOC in naïve populations. In addition, the bivalent formulation confers protection against viral challenge with SARS-CoV-2 prototype D614G strain as well as Alpha and Beta variant strains in hamsters. We show that a primary immunization with the bivalent CoV2 preS dTM-AS03 elicits broader and durable (1 year) neutralizing antibody responses against VOC including Omicron BA.1 and BA.4/5, and SARS-CoV-1 as compared to the ancestral D614 or Beta variant monovalent vaccines in naïve non-human primates. We conducted immunogenicity and challenge studies in macaques and hamsters using a bivalent recombinant vaccine formulation containing the SARS-CoV-2 prefusion-stabilized Spike trimers of the ancestral D614 and the variant Beta strains with AS03 adjuvant (CoV2 preS dTM-AS03) in a primary immunization setting. Effective COVID-19 vaccine strategies are required to achieve broad protective immunity against current and future VOC. Since the beginning of the COVID-19 pandemic, several variants of concern (VOC) have emerged for which there is evidence of an increase in transmissibility, more severe disease, and/or reduced vaccine effectiveness.

Protein in vaccine