SARS-CoV-2 mRNA Vaccine Induces Robust Specific and Cross-reactive IgG and Unequal Neutralizing Antibodies in Naïve and Previously Infected Recipients

Abstract

Understanding vaccine-mediated protection against SARS-CoV-2 is critical to overcoming the global COVID-19 pandemic. We investigate mRNA vaccine-induced antibody responses against the reference strain, seven variants, and seasonal coronaviruses in 168 healthy individuals at three-time points: before vaccination, after the first, and after the second doses. Following complete vaccination, both naïve and previously infected individuals developed comparably robust SARS-CoV-2 spike antibodies and variable levels of cross-reactive antibodies to seasonal coronaviruses. However, the strength and frequency of SARS-CoV-2 neutralizing antibodies in naïve individuals were lower than in previously infected individuals. After the first vaccine dose, 1/3 ^rd of previously infected individuals lacked neutralizing antibodies; this was improved to 1/5 ^th after the second dose. In all individuals, neutralizing antibody responses against the Alpha and Delta variants were weaker than against the reference strain. Our findings support future tailored vaccination strategies against emerging SARS-CoV-2 variants as mRNA-vaccine-induced neutralizing antibodies are highly variable among individuals.

Graphical Abstract

Abstract

Narowski et al. investigate mRNA vaccine-induced antibody responses in 168 healthy individuals with longitudinal specimens. After complete vaccination, both previously infected and naïve individuals develop comparably robust SARS-CoV-2 spike antibodies. However, neutralizing antibody response to vaccination is variable among these individuals, supporting future tailored vaccination strategies against emerging SARS-CoV-2 variants.