Durability of the Neutralizing Antibody Response to mRNA Booster Vaccination Against SARS-CoV-2 BA.2.12.1 and BA.4/5 Variants

Abstract

The recent emergence of the SARS-CoV-2 BA.4/5 and BA.2.12.1 variants has led to rising COVID-19 case numbers and concerns over the continued efficacy of mRNA booster vaccination. Here we examine the durability of neutralizing antibody (nAb) responses against these SARS-CoV-2 Omicron subvariants in a cohort of health care workers 1-40 weeks after mRNA booster dose administration. Neutralizing antibody titers fell by ~1.5-fold 4-6 months and by ~2.5-fold 7-9 months after booster dose, with average nAb titers falling by 11-15% every 30 days, far more stable than two dose induced immunity. Notably, nAb titers from booster recipients against SARS-CoV-2 BA.1, BA.2.12.1, and BA.4/5 variants were ~4.7-, 7.6-, and 13.4-fold lower than against the ancestral D614G spike. However, the rate of waning of booster dose immunity was comparable across variants. Importantly, individuals reporting prior infection with SARS-CoV-2 exhibited significantly higher nAb titers compared to those without breakthrough infection. Collectively, these results highlight the broad and stable neutralizing antibody response induced by mRNA booster dose administration, implicating a significant role of virus evolution to evade nAb specificity, versus waning humoral immunity, in increasing rates of breakthrough infection.

Omicron breakthrough infections after triple‐dose inactivated COVID‐19 vaccination: A comprehensive analysis of antibody and T‐cell responses

“…However, the rate of this decline after the third dose of the booster was relatively slower. Further linear regression analysis also showed that the decreasing trends of antibodies against WT, Alpha, Beta, and Delta were generally comparable, which is in alignment with previous findings regarding mRNA vaccines [11,33]. Our study evaluated individuals up to 10-12 months following their third dose, during which most participants maintained relatively stable neutralizing antibodies, suggesting good persistence of the antibody response against these VOCs.…”

“…Investigations into mRNA vaccine boosters have revealed that a third administration of homologous mRNA vaccine boosters can markedly enhance the neutralization titres against various VOCs, including Omicron, attaining a seropositivity rate approaching 100% [7,[11][12][13]. Additionally, a few studies have indicated that the humoral immune response provided by the booster mRNA vaccine lasts at least 6-9 months [14], and memory CD4 + T cells last at least 3 months [15].…”

Vaccine waning and immune escape drive the second surge of Omicron spread in Hong Kong: A modeling study

“…A discrete-time model with vaccination was developed based on SEIR framework [17][18][19][20][21][22]. The model assumed that the whole population was initially susceptible (S group) and there would be partial population from S group received the first dose of vaccine every day.…”

“…Second, BA 4 and BA. 5 were not separated in the model [22]. Finally, there was complete cross-immunity between these two types, which meant that recovered individuals with either virus lead to immunity to both.…”

Omicron-adapted vaccines might require longer follow-up to reveal true benefits

“… 10 A longer affinity maturation process since first exposure in Wuhan-Hu-1 booster recipients might also contribute to more durable neutralisation activity against omicron subvariants than in primary vaccination recipients. 11 We expect more long-term than immediate benefits after omicron-adapted booster vaccination, which, given sufficient time, might better protect against current and emerging omicron subvariants than Wuhan-Hu-1 boosters.…”