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.

Background: The emergence of the Omicron variant (B.1.1.529), which correlated with dramatic losses in cross-neutralization capacity of post-vaccination sera, raised concerns about the effectiveness of COVID-19 vaccines against infection and disease. Several clinically relevant sub-variants subsequently emerged rapidly. Methods: We evaluated published and pre-print studies reporting sub-variant specific reductions in cross-neutralization compared to the prototype strain of SARS-CoV-2 and between sub-variants. Median fold-reduction across studies was calculated by sub-variant and vaccine platform. Results: Among 178 studies with post-vaccination data, after primary vaccination the sub-variant specific fold-reduction in neutralization capacity compared to the prototype antigen varied widely, from median 4.2-fold for BA.3 to 40.1-fold for BA.2.75; in boosted participants fold-reduction was similar for most sub-variants (5.3-fold to 7.0-fold); however, a more pronounced fold-change was observed for sub-variants related to BA.4 and BA.5 (10.4-fold to 14.2-fold). Relative to BA.1, the other Omicron sub-variants had similar neutralization capacity post-primary vaccination (range median 0.8-fold to 1.1-fold) and post-booster (0.9-fold to 1.4-fold) except for BA.4/5-related sub-variants which was higher (2.1-fold to 2.7-fold). Omicron sub-variant-specific responder rates were low post-primary vaccination (range median 28.0% to 65.9%) compared to the prototype (median 100%) but improved post-booster (range median 73.3% to 100%). Conclusions: Fold-reductions in neutralization titers were comparable post-booster except for sub-variants related to BA.4 and BA.5, which had higher fold-reduction. Assessment after primary vaccination was not possible because of overall poor neutralization responses causing extreme heterogeneity. Considering large fold-decreases in neutralization titers relative to the parental strain for all Omicron sub-variants, vaccine effectiveness is very likely to be reduced against all Omicron sub-variants, and probably more so against variants related to BA.4 or BA.5.

Using a non-human primate model, we evaluated an RSV pre-fusion F and G protein virus-like particle-based maternal immunization strategy and evaluated the effects of pregnancy on vaccine-induced immunity against RSV. Immunization during pregnancy induced robust systemic and mucosal IgG and neutralizing antibody titers. Upon post-partum challenge, this vaccination strategy enhanced humoral recall responses and Fc-effector functions, and reduced viral load in dams. Infants born to vaccinated dams had increased levels of RSV antibodies in the plasma and lung mucosa, which were correlated with reduced viral load; these infants also exhibited reduced pulmonary eosinophilia. Interestingly, vaccination during pregnancy was associated with increased post-fusion F responses and NAb titers, and we observed a reduction in viral load following post-partum challenge compared to nonpregnant controls. These results support the potential of a VLP-based maternal immunization strategy and provide insight into vaccine-induced immunity against RSV in pregnant and post-partum adults and infants.