Figure - available from: Vaccines
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(upper panel) Logistic regression of factors influencing the detectability of the neutralizing antibody to Omicron BA.5, XBB.1.5, and EG.5 variants. (top 3 panels). (lower panel) Linear regression of factors influencing the neutralizing antibody titers to Wuhan and Omicron BA.5, XBB.1.5, and EG.5 variants in those with detectable levels. (bottom 4 panels).
Source publication
We determined neutralizing antibody levels to the ancestral Wuhan SARS-CoV-2 strain and three Omicron variants, namely BA.5, XBB.1.5, and EG.5, in a heavily vaccinated cohort of 178 adults 15–19 months after the initial vaccine series and prospectively after 4 months. Although all participants had detectable neutralizing antibodies to Wuhan, the pr...
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Citations
... Humoral immunity has received significant attention, and it has been shown that vaccines and infections induce circulating antibodies which, however, wane with time (4,5). Even though breakthrough infections induce broadly neutralizing antibodies, the neutralization capacity against emerging variants wanes (6,7). In addition to humoral immunity, cell-mediated immunity is strongly induced by the SARS-CoV-2 vaccines and infections. ...
Introduction
Mutations occurring in the spike (S) protein of SARS-CoV-2 enables the virus to evade COVID-19 vaccine- and infection-induced immunity.
Methods
Here we provide a comprehensive analysis of humoral and cell-mediated immunity in 111 healthcare workers who received three or four vaccine doses and were followed up to 12 and 6 months, respectively, after the last vaccine dose. Omicron breakthrough infection occurred in 71% of the vaccinees, enabling evaluation of vaccine- and vaccine/infection-induced hybrid immunity.
Results
Neutralizing antibodies were the highest against the ancestral D614G and were sequentially reduced against the Omicron variants BA.2, BA.5 and XBB.1.5. S1-specific IgG and neutralizing antibody levels were significantly higher in infected than in uninfected vaccinees, and the fourth vaccine dose in combination with a breakthrough infection resulted in high neutralizing antibody levels against all variants. T cell-mediated immunity, instead, was well retained already after two vaccine doses, and was not significantly strengthened by additional booster vaccine doses or Omicron breakthrough infections.
Discussion
While humoral immunity is sensitive to mutations in the S protein and thus declined rapidly, the cell-mediated immunity is durable to antigenic variation, which may explain the good efficacy of COVID-19 vaccines against a severe disease.
... However, the relationship between antibody levels and protection against Omicron sub-variants remains less clear. While some studies have demonstrated a correlation between neutralizing capacity and antibody levels with protection against BA.1, BA.2 (14)(15)(16)(17), and BA.4/5 (18) variants, others have found inconsistent results (19)(20)(21), especially for the subsequent sub-variants BQ.1 and XBB (22)(23)(24)(25). These discrepancies highlight the need for a deeper understanding of the immune correlates of protection in the context of evolving SARS-CoV-2 variants. ...
... Hybrid immunity, resulting from a combination of vaccination and natural infection, has been shown to induce higher and more durable antibody responses compared to vaccination or infection alone (36)(37)(38)(39)(40). Nevertheless, the extent to which hybrid immunity confers protection against newer Omicron sub-variants is not fully understood (11,18,22,38,41). Additionally, the impact of prior infections and the timing of these infections on the protection against these subvariants warrants further investigation. ...
... However, other studies found no consistent association, with some reporting a link between antibody levels and protection against BA.1 but not BA.2 (19)(20)(21). Regarding BA.5, BQ.1, and XBB variants, some research suggests higher IgG levels increase protection against BA.4/5 infection (18,22,47) and XBB infection (24,25), but other studies found no correlation during BA.5 and XBB waves (22,23). These conflicting results may be due to variations in study design, sample size, duration of follow-up, previous infection status of the participants and differences in neutralization and antibody level measurement assays. ...
The ongoing evolution of SARS-CoV-2, particularly through the emergence of new variants, continues to challenge our understanding of immune protection. While antibody levels correlate with protection against earlier variants like Alpha and Delta, their relationship with Omicron sub-variants remains unclear. To investigate the role of antibody levels and neutralizing activity in preventing breakthrough infections, we analyzed longitudinal SARS-CoV-2 humoral responses and neutralizing activity against the ancestral virus and major emerging variants in a well-characterized cohort of healthcare workers in Spain (N = 405). We found that antibody levels and neutralization titers are key indicators of protection against SARS-CoV-2, including the BQ.1 and XBB Omicron variants. Higher IgG and IgA levels were associated with protection over three 6-month follow-up periods sequentially dominated by BA.1, BA.2, BA.5, BQ.1, and XBB Omicron sub-variants, although the strength of the association between antibody levels and protection declined over time. Our findings demonstrate that binding antibody levels and neutralizing responses are a valid correlate of protection against more evasive BQ.1 and XBB Omicron variants, although the strength of this association declined over time. Additionally, our results underscore the importance of continuous monitoring and updating vaccination strategies to maintain effective protection against emerging SARS-CoV-2 variants.
