Blog

(***P <0.001, *P <0.05, ns is not significant, by pairedt-test). airways. By contrast, the monovalent Prototype vaccine no longer offered good protection, and breakthrough infections were observed in all animals and tissues. Thus, based on these study results, the protein-based XBB.1.5 vaccine is immunogenic and increased the breadth of protection against the Omicron EG.5.1 variant in the Syrian hamster model. == IMPORTANCE == As SARS-CoV-2 continues to evolve, there is a need to assess the immunogenicity and efficacy of updated vaccines against newly emerging variants in pre-clinical models such as mice and hamsters. Here, we compared the immunogenicity and efficacy URB602 between the updated XBB.1.5, the original Prototype Wuhan-1, and the bivalent Prototype + BA.5 vaccine against a challenge with the EG.5.1 Omicron variant of SARS-CoV-2 in hamsters. The XBB.1.5 and bivalent vaccine, but not the Prototype, induced serum-neutralizing antibodies against EG.5.1, albeit the titers were higher in the XBB.1.5 immunized hamsters. The presence of neutralizing antibodies was associated with complete protection against EG.5.1 infection in the lower airways and reduced virus titers in the upper airways. Compared with the bivalent vaccine, immunization with XBB.1.5 improved viral control in the nasal turbinates. Together, URB602 our data show that the updated vaccine is immunogenic and that it offers better protection against recent variants of SARS-CoV-2. KEYWORDS:COVID-19 vaccine, SARS-CoV-2 URB602 variants, hamsters (preclinical animal models), B and T cell analysis, vaccine efficacy, EG.5.1 variant == INTRODUCTION == Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused hundreds of millions of infections worldwide and over 7 million deaths. Vaccines targeting the SARS-CoV-2 Spike (S) protein were developed within 1 year of the start of the pandemic, and they were remarkably effective in protecting against severe coronavirus disease 2019 (COVID-19), with efficacy rates ranging from 75% to 95%, depending on the vaccine, the circulating strain, and age of the individual (13). In November 2021, the Omicron variant of SARS-CoV-2 emerged, quickly spreading globally, and replacing previous variants of concern (VOC) of SARS-CoV-2. Omicron variants harbor more than 30 amino acid substitutions in the S protein, which results in the evasion of humoral immune responses and escape from the Mouse monoclonal to Myostatin protection of the original vaccines (4). The Omicron URB602 lineage of SARS-CoV-2 has continued to evolve away from neutralizing antibodies generated by previous infection or vaccination with ancestral vaccines, a process referred to as antigenic drift. Because of this drift, in 2022, global regulatory agencies recommended updating the COVID-19 vaccine to include the BA.5 variant of SARS-CoV-2. In late 2022, XBB-lineage Omicron variants of SARS-CoV-2 emerged and became predominant (5). The XBB variants were resistant to antibodies induced by the BA.5 vaccine, prompting another update of the COVID-19 vaccine; the monovalent XBB.1.5 vaccine (6). Due to the continued evolution and drift of the SARS-CoV-2 virus, the ability of the updated vaccines to generate cross-protective immunity against future viral variants is crucial and must be evaluated in preclinical animal models. Novavax, Inc. developed a SARS-CoV-2 recombinant S protein nanoparticle vaccine comprising full-length prefusion S trimers co-formulated with a saponin-based adjuvant, Matrix-M (Prototype rS). In preclinical studies in mice and non-human primates, this vaccine was effective against a homologous challenge with SARS-CoV-2 (7,8). Similarly, in mice, a Beta (B.1.351 rS) version of this vaccine was effective against heterologous challenge with the Omicron BA.1 variant of SARS-CoV-2 (9). In Syrian hamsters, we showed that a boost with the BA.5 rS vaccine offered robust protection against a BA.5 virus challenge (10). In humans, immunization with the monovalent Prototype rS vaccine was effective against mild, moderate, or severe COVID-19 in clinical trials (1113). Several trials reported the vaccine efficacy against symptomatic infection of 96% for the ancestral strain of SARS-CoV-2 and 86% for the alpha (B.1.1.7) variant (13,14). Boosting with a third or fourth dose of Prototype rS vaccine reduced the antigenic distance between the ancestral and Omicron BA.4/5 variants of SARS-CoV-2 (15,16), suggesting that repeated exposure to a subunit vaccine containing ancestral S protein induces a cross-reactive and -neutralizing antibody response. Here, we evaluated the immunogenicity and efficacy of protein-based nanoparticle vaccines containing recombinant S.