Systematic review and meta-analysis of the factors affecting waning of post-vaccination neutralizing antibody responses against SARS-CoV-2

Abstract

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.

Global variation in prior exposure shapes antibody neutralization profiles of SARS-CoV-2 variants up to BA.2.86

“…A longitudinal sampling from the same cohort/trial will be needed for a definitive conclusion. Previous studies have observed faster waning of titers against Omicron variants than against Anc./D614G after bivalent vaccination Jacobsen et al 2023;Chalkias et al 2022),.…”

Current German Recommendations and International Research on the Use of COVID-19 Boosters among Health Care Providers in 2024: A Narrative Review

“…COVID-19 boosters in these individuals aim to reduce their occupational risk of infection and transmission to vulnerable populations. Bivalent boosters may provide protection against hospitalisation and severe symptoms caused by various SARS-CoV-2 variants [ 7 , 8 , 26 , 27 , 28 ], particularly in individuals with “hybrid immunity” [ 1 , 2 , 3 , 4 , 5 , 7 , 8 ]. Such boosters can enhance both humoral and cellular immunity, decrease infection rates, and offer protection, especially for specific populations such as organ transplant recipients, dialysis patients, individuals with chronic renal disease, the elderly population, and immunocompromised individuals [ 7 ].…”

“…In contrast, individuals with “hybrid immunity”, resulting from both vaccination and infection, may experience enhanced protection against severe symptoms. This phenomenon is attributed to a broader recognition of different Ags not included in the vaccine design and the subsequent boosting of mucosal immunity [ 2 , 3 , 4 , 5 ]. The emergence of the Omicron variant (B.1.1.529) suggests that the spike protein of this viral variant may elicit broader SARS-CoV-2 protective immunity against the emerging variant(s) [ 1 ].…”

A single-dose MCMV-based vaccine elicits long-lasting immune protection in mice against distinct SARS-CoV-2 variants

“…This feature is unique for this vector and superior to other vaccine formulations, which require repeated booster administrations to avoid immune waning over time (47, 48, 52, 53). Considering that neutralizing antibodies against SARS-CoV-2 wane at similar rates upon infection or vaccination with currently used vaccines (9, 46, 54-56), our vaccine might provide an immunity that is even better than that induced by infection.…”

“…Numerous COVID-19 vaccines that induce immune responses against the S glycoprotein have been developed and authorized for use with unprecedented speed. However, vaccine-induced immunity wanes within months, resulting overall in reduced protection against infections and disease (4, 7-9). In addition, emerging variants have been increasingly capable of escaping vaccine-induced immunity driving the need for continued vaccine adaptation and booster shots (10-12).…”