Attenuation of antibody titres during 3-6 months after the second dose of the BNT162b2 vaccine depends on sex, with age and smoking as risk factors for lower antibody titres at 6 months

Objective: We aimed to determine antibody titres at 6 months and their rate of change during 3-6 months after the second dose of the BNT162b2 coronavirus disease 2019 (COVID-19) mRNA vaccine (Pfizer/BioNTech) and to explore clinical variables associated with titres in Japan. Methods: We enrolled 365 healthcare workers (250 women, 115 men) whose 3-month antibody titres were analyzed in our previous study and whose blood samples were collected 183 plus or minus 15 days after the second dose. Participant characteristics collected previously were used. The relationships of these factors with antibody titres at 6 months and rates of change in antibody titres during 3-6 months were analyzed. Results: Median age was 44 years. Median antibody titre at 6 months was 539 U/mL. Older participants had significantly lower antibody titres (20s, 752 U/mL; 60s-70s, 365 U/mL). In age-adjusted analysis, smoking was the only factor associated with lower antibody titres. Median rate of change in antibody titres during 3-6 months was -29.4%. The only factor significantly associated with the rate of change in Ab titres was not age or smoking, but sex (women, -31.6%; men, -25.1%). Conclusion: The most important factors associated with lower antibody titres at 6 months were age and smoking, as at 3 months, probably reflecting their effect on peak antibody titres. However, antibody titres significantly attenuated during 3-6 months in women alone, which reduced the sex difference in antibody titres seen during the first 3 months. Antibody titres may be affected by different factors at different time points.