Search

The article discusses the additional challenges for the next phase of SARS-CoV-2 vaccines, including optimizing the immunological rationale for boosting and the best approaches for building a future-proofed immune repertoire to protect against oncoming viral variants. Some people favor frequent boosting with the first-generation, ancestral spike vaccines, while others propose frequent readjustment using current variant sequences, polyvalent vaccines, or pan-coronavirus strategies.

In efforts to synthesize a clear understanding of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) protective immunity, antibody analysis has been paralleled by T cell studies across asymptomatic, mild, and severe COVID-19 (coronavirus disease 2019). Defining CD4 and CD8 effector functions in protection is important, considering that antibody responses appear short-lived and T cell memory is potentially more durable. To fully understand population-level immunity, screening for both antibody and T cell immunity using standardized testing methods would be beneficial. [ABSTRACT FROM AUTHOR]

The article presents the discussion on vaccines preventing disease primarily by eliciting neutralizing antibodies and preventing the ability of SARSCoV-2 for infecting cells. Topics include reducing vaccine-induced immune protection for emerging variants showing mutations in the spike protein; and people developing diverse neutralizing antibody titers after vaccination.

The impact of the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infecting strain on downstream immunity to heterologous variants of concern (VOCs) is unknown. Studying a longitudinal healthcare worker cohort, we found that after three antigen exposures (infection plus two vaccine doses), S1 antibody, memory B cells, and heterologous neutralization of B.1.351, P.1, and B.1.617.2 plateaued, whereas B.1.1.7 neutralization and spike T cell responses increased. Serology using the Wuhan Hu-1 spike receptor binding domain poorly predicted neutralizing immunity against VOCs. Neutralization potency against VOCs changed with heterologous virus encounter and number of antigen exposures. Neutralization potency fell differentially depending on targeted VOCs over the 5 months from the second vaccine dose. Heterologous combinations of spike encountered during infection and vaccination shape subsequent cross-protection against VOC, with implications for future-proof next-generation vaccines.

Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection., (Copyright © 2020, American Association for the Advancement of Science.)