B-077 Comparison of SARS-CoV-2 Antibody Profile and Omicron-Specific Neutralizing Activity Before and After mRNA Booster Vaccines: Bivalent vs. Original Formulation
Authors: Windau A , Meyers J , Yang X , Pontoni R , Schmotzer C , Noguez J , Dong F , Zhang X S 
Published: September 2023

Abstract

Background
With entering into the era of SARS-CoV-2 vaccine boosters and shifting from pandemic to endemic, understanding how boosters change antibody levels and durability is important for vaccination strategies. This study investigated antibodies against different antigens and neutralizing antibody levels in immunocompetent healthcare workers who have received the primary 2 doses and booster mRNA vaccines.

Method
The study included two cohorts. Cohort 1 received 3 doses of the original vaccine and cohort 2 received the 3 original doses plus the 4th bivalent booster. Two blood samples were collected from each participant before the 3rd (pre-3) or 4th dose (pre-4) and 14–30 days after the 3rd (post-3) or 4th dose (post-4). SARS-CoV-2 IgG antibodies against the spike protein receptor-binding domain (RBD), S1, S2, and nucleocapsid protein were measured using a semi-quantitative multiplex assay on a Bioplex 2200 analyzer. Neutralizing antibodies against omicron sublineage BA.2 were determined using a surrogate virus neutralization assay.

Results
Among the 45 participants aged 24 to 66, 53% had natural infection evidenced by positive anti-nucleocapsid IgG or historical PCR results. In cohort 1 (n = 24), the median time between the second and third doses was 375 (range 278–439) days. In cohort 2 (n = 21), the median time between the third and fourth doses was 353 (range 102–438) days. Both the 3rd original and 4th bivalent vaccines significantly increased neutralizing, anti-RBD, anti-S1 and anti-S2 antibodies when compared to their pre-dose concentrations (P &lt; 0.01). The median and interquartile range (IQR) for pre-and post-booster antibody levels were: Neutralizing antibody post-3 median: 189 U/mL (IQR 99–781) versus pre-3 median: 44 U/mL (IQR 0–180), post-4 median: 241 U/mL (IQR 148–630) versus pre-4 median: 37 U/mL (IQR 8–167); anti-RBD post-3 median: 13 100 U/mL (IQR 8001–31 850) versus pre-3 median: 3437 U/mL (IQR 201–7976), post-4 median: 16 490 U/mL (IQR 7691–24 710) versus pre-4 median: 3270 U/mL (IQR 1970–4847); anti-S1 post-3 median: 9700 U/mL (IQR 7281–27 425) versus pre-3 median: 2287 U/mL (IQR 229–7710), post-4 median: 11 000 U/mL (IQR 6935–20 665) versus pre-4 median: 2280 U/mL (IQR 1419–2833); and anti-S2 post-3 median: 148 U/mL (IQR 89–266) versus pre-3 median: 25 U/mL (IQR 9–51), post-4 median: 101 U/mL (IQR 73–280) versus pre-4 median: 28 U/mL (IQR 14–43). No difference was found between the post-4-bivalent and post-3-original antibody levels. The difference in post/pre ratios elicited by the 3rd and 4th doses was also not statistically significant (P &gt; 0.05). Further analysis showed participants with natural COVID infection had much higher pre-3 and pre-4 dose antibody levels than those without natural infection (P &lt; 0.01). The pre-booster neutralizing antibody levels of infected participants were not significantly different (P &gt; 0.05) from the post-booster levels of the non-infected participants. This pattern was consistent across antibodies against different antigens. In addition, there was no significant difference in post-booster antibodies between previously infected and non-infected participants.

Conclusion
The bivalent and original mRNA vaccines are equally effective in enhancing immunity against SARS-CoV-2. Individuals with no previous COVID infection may need boosters annually to raise waning antibodies. Naturally infected individuals demonstrated long-lasting immunity and may not require annual boosters.