Mass COVID-19 vaccination and continued introduction of new SARS-CoV-2 variants increased prevalence of hybrid immunity at various stages of waning protection. We systematically reviewed waning of post-vaccination neutralizing antibody titers in different immunological settings to investigate differences. We searched published and pre-print studies providing post-vaccination neutralizing antibody responses against the Index strain or Omicron BA.1. We used random effects meta-regression to estimate fold-reduction from months 1 to 6 post last dose by primary vs booster regimen and infection-naïve vs hybrid-immune cohorts. Among 26 eligible studies, 65 cohorts (range 3–21 per stratum) were identified. Month-1 titers varied widely across studies within each cohort and by vaccine platform, number of doses and number of prior infections. In infection-naïve cohorts, the Index strain waned 5.1-fold (95%CI: 3.4–7.8; n = 19 cohorts) post-primary regimen and 3.8-fold (95%CI: 2.4–5.9; n = 21) post-booster from months 1 to 6, and against Omicron BA.1 waned 5.9-fold (95%CI: 3.8–9.0; n = 16) post-booster; Omicron BA.1 titers post-primary were too low to assess. In hybrid-immune, post-primary cohorts, titers waned 3.7-fold (95%CI: 1.7–7.9; n = 8) against the Index strain and 5.0-fold (95%CI: 1.1–21.8; n = 6) against Omicron BA.1; post-booster studies of hybrid-immune cohorts were too few (n = 3 cohorts each strain) to assess. Waning was similar across vaccination regimen and prior-infection status strata but was faster for Omicron BA.1 than Index strains, therefore, more recent sub-variants should be monitored. Wide differences in peak titers by vaccine platform and prior infection status mean titers drop to non-protective levels sooner in some instances, which may affect policy.

Objective: COVID-19 vaccine-neutralizing antibodies provide early data on potential vaccine effectiveness, but their usefulness depends on study reliability and reporting quality. Methods: We systematically evaluated 50 published post-vaccination neutralizing antibody studies for key parameters that determine study and data quality regarding sample size, SARS-CoV-2 infection, vaccination regimen, sample collection period, demographic characterization, clinical characterization, experimental protocol, live virus and pseudo-virus details, assay standardization, and data reporting. Each category was scored from very high to low or unclear quality, with the lowest score determining the overall study quality score. Results: None of the studies attained an overall high or very high score, 8% (n = 4) attained moderate, 42% (n = 21) low, and 50% (n = 25) unclear. The categories with the fewest studies assessed as ≥ high quality were SARS-CoV-2 infection (42%), sample size (30%), and assay standardization (14%). Overall quality was similar over time. No association between journal impact factor and quality score was found. Conclusions: We found that reporting in neutralization studies is widely incomplete, limiting their usefulness for downstream analyses.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the virus responsible for the coronavirus disease (COVID-19) pandemic. It was first detected in Wuhan, China, in late December of 2019 and, as of April 2021, has infected over 140 million people worldwide, resulting in three million deaths. Scientists across the globe have worked tirelessly over the past year and have developed four vaccines currently licenced by the European Medicines Agency. In late 2020, several variants of concern established themselves globally; including the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1 (Gamma) variants which have several concerning mutations. Initial data has shown that these variants can be more infectious and even escape antibody neutralisation. This means natural immunity from past infection and even vaccination may not be enough to bring the pandemic to an end. Understanding how the virus's entry is facilitated by its spike protein is essential to testing the antibodies' efficacy and understanding the pitfalls of previous research. The knowledge gained on the importance of the variants' mutations and how they may evade antibodies are key to developing novel monoclonal antibodies (mAbs), updated vaccines, and finally the research into preventing future variants via mAb cocktails and ones that target conserved epitopes. This study explored the relationship between mAbs and the SARS-CoV-2 spike protein and how it is augmented in response to the novel variants and in what manner issues may be overcome.