ABSTRACT
The SARS-CoV-2 Omicron variant evades vaccine-induced immunity. While a booster dose of ancestral mRNA vaccines effectively elicits neutralizing antibodies against variants, its efficacy against Omicron in older adults, who are at the greatest risk of severe disease, is not fully elucidated. Here, we evaluated multiple longitudinal immunization regimens of mRNA BNT162b2 to assess the effects of a booster dose provided >8 months after the primary immunization series across the murine lifespan, including in extremely aged 21-month-old mice. Boosting dramatically enhanced humoral and cell-mediated responses with evidence of Omicron cross-recognition. Furthermore, while younger mice were protected without a booster dose, boosting provided sterilizing immunity against Omicron-induced lung infection in extremely aged mice. Correlational analyses revealed that neutralizing activity against Omicron was strongly associated with protection. Overall, our findings indicate age dependent vaccine efficacy and demonstrate the potential benefit of mRNA booster immunization to protect vulnerable older populations against SARS-CoV-2 variants.
ABSTRACT
The U.S. Centers for Disease Control and Prevention (CDC) and other health agencies have recently recommended a booster dose of COVID-19 vaccines for specific vulnerable groups including adults 65 years and older. There is limited evidence whether vaccine effectiveness in older adults decreases over time, especially against severe COVID-19. We performed a rapid review of published studies available through 04 November 2021 that provide effectiveness data on mRNA vaccines approved/licensed in the United States and identified eight eligible studies which evaluated vaccine effectiveness in older adults. There is evidence of a decline in vaccine effectiveness against both SARS-CoV-2 infection and severe COVID-19 in older adults among studies which analyzed data up to July-October 2021. Our findings suggest that vaccine effectiveness diminishes in older adults, which supports the current recommendation for a booster dose in this population.
Subject(s)
COVID-19ABSTRACT
Development of affordable and effective vaccines that can also protect vulnerable populations such as the elderly from COVID-19-related morbidity and mortality is a public health priority. Here we took a systematic and iterative approach by testing several SARS-CoV-2 protein antigens and adjuvants to identify a combination that elicits neutralizing antibodies and protection in young and aged mice. In particular, SARS-CoV-2 receptorbinding domain (RBD) displayed as a protein nanoparticle (RBD-NP) was a highly effective antigen, and when formulated with an oil-in-water emulsion containing Carbohydrate fatty acid MonoSulphate derivative (CMS) induced the highest levels of cross-neutralizing antibodies compared to other oil-in-water emulsions or AS01B. Mechanistically, CMS induced antigen retention in the draining lymph node (dLN) and expression of cytokines, chemokines and type I interferon-stimulated genes at both injection site and dLN. Overall, CMS:RBD-NP is effective across multiple age groups and is an exemplar of a SARS-CoV-2 subunit vaccine tailored to the elderly.