Serum neutralization of SARS-CoV-2 Omicron sublineages BA.1 and BA.2, and cellular immune responses 3 months after booster vaccination.

OBJECTIVES: We investigated serum neutralizing activity against BA.1 and BA.2 Omicron sublineages, and T cell response before and 3 months after booster vaccine in healthcare workers (HCWs).

METHODS: HCWs aged 18-65 years, vaccinated and boosted with the BNT162b2 vaccine were included. Anti-SARS-CoV-2 IgG levels and cellular response (through IFNγ ELISpot assay) were evaluated in all participants, and neutralizing antibodies against Delta, BA.1 and BA.2 were evaluated in participants with at least one follow-up visit 1 or 3 months after the booster dose.

RESULTS: Among the 118 HCWs who received the booster dose, 102 and 84 participants attended the 1-month and 3-month visits, respectively. Before the booster vaccine dose, a low serum neutralizing activity against Delta, BA.1, and BA.2 was detectable in only n=39/102 (38.2%), n=8/102 (7.8%) and n=12/102 (11.8%) of the participants, respectively. At 3 months, neutralizing antibodies were detected in n=84/84 (100%), n=79/84 (94%) and n=77/84 (92%) against Delta, BA.1 and BA.2, respectively. Geometric mean titers (GMTs) of neutralizing antibodies against BA.1 and BA.2 were 2.2- and 2.8-fold reduced compared to Delta. From 1 to 3 months after the booster dose, participants with a recent history of SARS-CoV-2 infection (n=21/84) had persistent levels of S1 reactive specific T cells and of neutralizing antibodies against Delta and BA.2, and 2.2-fold increase in neutralizing antibodies against BA.1 (p= 0.014). Conversely, neutralizing antibody titers declined from 1 to 3 months after booster dose in individuals without any recent infection, against Delta (2.5-fold decrease, p<0.0001), BA.1 (1.5-fold, p=0.02) and BA.2 (2-fold, p<0.0001).

CONCLUSIONS: The booster vaccine dose provided significant and similar response against BA.1 and BA.2 Omicron sublineages, but the immune response declines in the absence of recent infection.