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Effect of previous SARS-CoV-2 infection on humoral and T-cell responses to single-dose BNT162b2 vaccine

Our take —

Immunogenicity to a single dose of BNT162b2 nCoV-19 (Pfizer) vaccine was evaluated in a small cohort in the UK where timing of the 2nd dose was delayed to 12 weeks. Immunogenicity was considerably higher (26x in neutralizing antibody and 10x in T cell responses) in those previously infected with SARS-CoV-2 (n=21) compared to infection-naive adults (n=51). Antibodies decreased with increasing age only in the infection-naive vaccinated adults. One infection-naive adult over age 50 years whose post-vaccination anti-S was very low (62 AU/ml) had PCR-confirmed symptomatic infection 5 weeks after vaccination. Prioritization for the 2nd dose to those without prior infection over age 50 or with other risk factors might minimize cases.

Study design

Prospective Cohort

Study population and setting

This was a small cohort study in the UK of 72 health care workers (HCWs) who were vaccinated with BNT162b2 (Pfizer) between Dec 23 and 31, 2020 and who provided a blood sample both at the time of the first dose and 21-25 days later. Adults (n=21) were classified as previously infected if they had pre-existing antibody (n=16) or strong T-cell responses to non-spike protein antigens in the post-vaccination specimen (n=5) which the vaccine does not induce. Infection-naïve adults (n=51) were negative for both of these measures. Anti-S antibody titer, SARS-CoV-2 live virus neutralizing antibody titer, and T-cell responses to SARS-CoV-2 peptide pools were assessed and compared by pre/post vaccination status, age and previous infection status.

Summary of Main Findings

Anti-S antibodies after a single dose of BNT162b2 nCoV-19 vaccine was significantly higher in those previously infected with SARS-CoV-2 compared to infection-naïve HCWs. Antibodies among infection-naive HCWs were lower in those over age 50 years than in those less than 50 years. One infection-naïve HCW over 50 years old with very low (62 AU/ml) anti-S antibodies post-vaccination had PCR-confirmed symptomatic infection 5 weeks after vaccination. Vaccine induced very strong neutralizing titers even in those with no or low detectable NT at baseline. Previously infected HCWs mounted stronger (10x) T-cell responses to spike peptides than infection-naïve HCWs, of which 50% had T-cell responses considered negative.

Study Strengths

Multiple immunological markers were evaluated, all showing consistent results, which is critical given that the true correlate of protection is unknown. HCWs were prospectively enrolled with blood specimens collected at the time of vaccination, thus enabling assessment of pre-infection status, and post-vaccination at a time when antibody response is at peak. Individual results were shown, enabling assessment of heterogeneity of responses within sub-groups.


This was a small study in a cohort that was not well characterized except for age and prior infection status, but the antibody responses were strikingly different by prior infection status suggesting the association is unlikely to be explained by another factor. Prior infection status was determined on immunological markers, not on confirmation of COVID-19 testing, which could account for some of the association; however, external data support their indication of prior infection status, and the immunological markers were infection-specific (i.e., not affected by vaccination). No correlates of immunity have been derived so implication for disease risk must be inferred, and the study was too small to evaluate impact on disease, but the one vaccine failure observed supported the findings that adults > age 50 years without prior infection may remain vulnerable after only a single dose. This study evaluated only the Pfizer vaccine; different findings (and thus recommendations) may be possible for ChAdOx1 (Oxford/AstraZeneca) in which observed no age effect on immunogenicity was observed in clinical trials.

Value added

This study showed clear evidence of lower antibody responses in individuals older than 50 years and in those without prior infection in adults immunized with a single dose of BNT162b2 (Pfizer) vaccine. Effectiveness studies should monitor the age and risk-factor status of breakthrough cases among those vaccinated as these finding suggest 2nd dose roll-out should consider prioritizing high-risk adults including those over 50 years of age.

This review was posted on: 12 March 2021