Long-Term Immunity and Antibody Response: Challenges for Developing Efficient COVID-19 Vaccines

Abstract

Questions and concerns regarding the efficacy and immunogenicity of coronavirus disease 2019 (COVID-19) vaccines have plagued scientists since the BNT162b2 mRNA vaccine was introduced in late 2020. As a result, decisions about vaccine boosters based on breakthrough infection rates and the decline of antibody titers have commanded worldwide attention and research. COVID-19 patients have displayed continued severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-spike-protein-specific antibodies and neutralizing antibodies in longitudinal studies; in addition, cytokine activation has been detected at early steps following SARS-CoV-2 infection. Epitopes that are highly reactive and can mediate long-term antibody responses have been identified at the spike and ORF1ab proteins. The N-terminal domain of the S1 and S2 subunits is the location of important SARS-CoV-2 spike protein epitopes. High sequence identity between earlier and newer variants of SARS-CoV-2 and different degrees of sequence homology among endemic human coronaviruses have been observed. Understanding the extent and duration of protective immunity is consequential for determining the course of the COVID-19 pandemic. Further knowledge of memory responses to different variants of SARS-CoV-2 is needed to improve the design of the vaccine.

A bioinformatic analysis of T-cell epitope diversity in SARS-CoV-2 variants: association with COVID-19 clinical severity in the United States population

“…Our findings support the hypothesis that long-lasting immunity against SARS-CoV-2 variants will be difficult to achieve through vaccines based solely on the spike protein and using neutralizing antibodies as an efficacy endpoint. One strategy to achieve long-term immunity against COVID-19 is the development of T-cell vaccines ( 9 , 55 ). When designing such vaccines, it is important that the epitopes selected are as invariant as possible and cover the maximum number of HLA haplotypes with even affinity distribution between HLA alleles ( 56 ).…”

Long-Term Cross Immune Response in Mice following Heterologous Prime-Boost COVID-19 Vaccination with Full-Length Spike mRNA and Recombinant S1 Protein

“…Although existing studies have shown that neutralizing antibody levels produced by vaccination or COVID-19 infection decrease over time, several investigations on the duration of antibody responses suggest long-term general humoral immunity can be observed up to 8 to 12 months after infection in convalescent patients [ 17 , 18 ]. The number of SARS-CoV-2 antigen-specific memory B cells remains stable for at least 6 to 12 months [ 18 ], and B-cell clonal selection and accumulation accompanied by neutralizing antibody release [ 19 ] support the persistence of humoral immunity after infection [ 20 ]. In terms of vaccine-induced immunity, Moderna studies have demonstrated that clinical trial participants maintained high levels of antibodies within 6 months after receiving the second dose of their mRNA-1273 vaccine [ 21 ].…”

Designing and developing a sensitive and specific SARS-CoV-2 RBD IgG detection kit for identifying positive human samples

“…The coronavirus disease 2019 (COVID-19) pandemic first arose in Wuhan, China, and the underlying agent is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1] . Disease presentation ranges from asymptomatic to multi-organ failure, with an overall fatality rate of 5% (95% CI 1-11) [2] , [3] , [4] , [5] , [6] .…”