Kinetics of Neutralizing Antibodies against Omicron Variant in Vietnamese Healthcare Workers after Primary Immunization with ChAdOx1-S and Booster Immunization with BNT162b2

Abstract

We studied the development and persistence of neutralizing antibodies against SARS-CoV-2 ancestral strain, and Delta and Omicron (BA.1 and BA.2) variants in Vietnamese healthcare workers (HCWs) up to 15 weeks after booster vaccination. We included 47 HCWs, including group 1 (G1, N = 21) and group 2 (G2; N = 26) without and with breakthrough Delta variant infection before booster immunization, respectively). The study participants had completed primary immunization with ChAdOx1-S and booster vaccination with BNT162b2. Neutralizing antibodies were measured using a surrogate virus neutralization assay. Of the 21 study participants in G1, neutralizing antibodies against ancestral strain, Delta variant, BA.1, and BA.2 were (almost) abolished at month 8 after the second dose, but all had detectable neutralizing antibodies to the study viruses at week 2 post booster dose. Of the 26 study participants in G2, neutralizing antibody levels to BA.1 and BA.2 were significantly higher than those to the corresponding viruses measured at week 2 post breakthrough infection and before the booster dose. At week 15 post booster vaccination, neutralizing antibodies to BA.1 and BA.2 dropped significantly, with more profound changes observed in those without breakthrough Delta variant infection. Booster vaccination enhanced neutralizing activities against ancestral strain and Delta variant compared with those induced by primary vaccination. These responses were maintained at high levels for at least 15 weeks. Our findings emphasize the importance of the first booster dose in producing cross-neutralizing antibodies against Omicron variant. A second booster to maintain long-term vaccine effectiveness against the currently circulating variants merits further research.

Figure 1.

Illustration showing the distribution of the study participants and sampling schedules for neutralizing antibody measurement. * After excluding cases with a SARS-CoV-2 infection episode recorded after the booster dose.

Figure 2.

Neutralizing antibodies against SARS-CoV-2 ancestral strain and variants of concerns (VOCs) (Delta, BA.1, and BA.2) in individuals without prior breakthrough Delta variant infection measured at different time points prior to booster vaccination and at week 2 post booster dose. (A) Back-to-back comparison between neutralizing antibody levels against VOCs. (B) Kinetics of neutralizing antibodies for individual participants. Horizontal dot lines indicate assay cut-off. Numbers indicate P values.

Figure 3.

Neutralizing antibodies against SARS-CoV-2 ancestral strain and variants of concerns (VOCs) (Delta, BA.1, and BA.2) in individuals with prior breakthrough Delta variant infection measured at different time points before booster vaccination and at week 2 post booster dose. (A) Back-to-back comparison between neutralizing antibody levels against VOCs. (B) Kinetics of neutralizing antibodies for individual participants. Horizontal dot lines indicate assay cut-off. Numbers indicates P values.

Figure 4.

Persistence of neutralizing antibodies at month 3 after the booster dose in those without documented breakthrough infection after the booster dose. (A) participants of G1, and (B) participants of G2. Horizontal dot lines indicate assay cutoff. Numbers indicates P values.