Slow waning of antibodies following a third dose of BNT162b2 in adults who had previously received two doses of inactivated vaccine

Introduction: Third doses of COVID-19 vaccination provide an important boost to immunity, reducing the risk of symptomatic infection and the risk of severe disease. Third doses have been particularly important for improving protection against variants. However, waning of clinical protection particularly against Omicron has been noted after receipt of third doses. Methods: We administered BNT162b2 as a third dose to adults aged [≥]30 years who had previously received two doses of inactivated vaccination. We collected blood before the third dose and again after one month and six months, and tested sera using a spike receptor binding domain IgG enzyme-linked immunosorbent assay, a surrogate virus neutralization test, and live virus plaque reduction neutralization assay against ancestral virus and Omicron BA.2. Results: We administered BNT162b2 as a third dose to 314 adults. We found robust antibody responses to the ancestral strain at six months after receipt of BNT162b2. Antibody responses to Omicron BA.2 were weaker after the third dose and had declined to a low level by six months. From a small number of participants we observed that natural infection or a fourth dose of vaccination generated similar antibody levels against ancestral virus, but infection generated higher antibody level against Omicron BA.2 than vaccination, suggesting a potential advantage in the breadth of antibody response from hybrid immunity. Conclusions: While antibody levels against the ancestral strain remained robust at six months after the third dose, antibody levels against Omicron BA.2 had fallen to low levels suggesting the potential benefits of a fourth dose.