Durability of response to the third dose of the SARS-CoV-2 BNT162b2 vaccine in adults aged 60 years and older: Three-month follow-up
Authors: Eliakim-Raz Noa , Stemmer Amos , Leibovici-Weisman Yaara , Ness Asaf , Awwad Muhammad , Ghantous Nassem , Erez Noam , Bareket-Samish Avital , Levy-Barda Adva , Ben-Zvi Haim , Moskovits Neta , Bar-Haim Erez , Stemmer Salomon M. 
Published: December 2021

AbstractBackgroundAge/frailty are strong predictors of COVID-19 mortality. After the second BNT162b2 dose, immunity wanes faster in older (≥65 years) versus younger adults. The durability of response after the third vaccine is unclear.MethodsThis prospective cohort study included healthcare workers/family members≥60 years who received a third BNT162b2 dose. Blood samples were drawn immediately before (T0), 10□19 (T1), and 74□103 (T2) days after the third dose. Anti-spike IgG titers were determined using a commercial assay, seropositivity was defined as≥50 AU/mL. Neutralising antibody titres were determined at T2. Adverse events, COVID-19 infections, and clinical frailty scale (CFS) levels were documented.FindingsThe analysis included 97 participants (median age, 70 years [IQR, 66□74], 58% CFS level 2). IgG titres, which increased significantly from T0 to T1 (medians, 440 AU/mL [IQR, 294□923] and 25,429 [14203□36114] AU/mL, respectively; p<0·001), decreased significantly by T2, but all remained seropositive (median, 8306 AU/mL [IQR, 4595□14701], p<0·001 vs T1). In a multivariable analysis, only time from the first vaccine was significantly associated with lower IgG levels at T2 (p=0·004). At T2, 60 patients were evaluated for neutralising antibodies; all were seropositive (median, 1294 antibody titre [IQR, 848□2072]). Neutralising antibody and anti-spike IgG levels were correlated (R=0·6, p<0·001). No major adverse events or COVID-19 infections were reported.InterpretationAnti-spike IgG and neutralising antibody levels remain adequate 3 months after the third BNT162b2 vaccine in healthy adults≥60 years, although the decline in IgG is concerning. A third vaccine dose in this population should be top priority.FundingNo external funding.Research in contextEvidence before this studyWe searched PubMed on Aug 1, 2021, for published research articles with no date restrictions, using the search terms of “SARS-Cov-2”, “COVID-19”, “vaccine”, “dose”, “antibody response”, and “adults” with English as a filter. Several studies were identified that investigated waning of immunity in healthy adults. It is well established through epidemiology and serology studies that in healthy adults, the protection conferred by the BNT162b2 messenger RNA (mRNA) vaccine (Pfizer/BioNtech) wanes significantly after several months. Studies have also shown that the immune response to the vaccine varies with age, and that after the second dose of the BNT162b2 vaccine, the older adult population (65-85 years of age) typically has a lower immune response (as reflected in an analysis of anti-spike IgG antibodies and neutralising antibody titres), than younger adults (18-55 years of age), and that the immunity wanes in all age groups within several months.Added value of this studyThis is, to our knowledge, the first study that examined anti-spike IgG and neutralising antibody titres three months after the third BNT162b2 vaccine dose. The study has demonstrated that three months after that dose, participants, who were healthy adults aged 60 years and older, remained anti-spike IgG seropositive, although a significant decrease in anti-spike IgG titres was observed (compared to two weeks after the third dose). In addition, a statistically significant correlation was observed between the neutralising antibody titres and the anti-spike IgG titres, and all participants were seropositive for neutralising antibodies three months after the third dose. Also, no major adverse events or COVID-19 infections were reported.Implications of all the available evidenceAs our data suggest that a third dose of the BNT162b2 vaccine is effective in maintaining adequate immune response against COVID-19 for at least several months in healthy adults aged 60 years and older, and as it is well established that older adults are at higher risk of severe COVID-19 disease and COVID-19 mortality, providing a third dose to this population should be a top priority. Our data also highlight that understanding the waning of the immune response in other age groups is key for making evidence-based policies regarding booster vaccinations for the population at large.