Immunogenicity of Pfizer-BioNTech COVID-19 mRNA Primary Vaccination Series in Recovered Individuals Depends on Symptoms at Initial Infection

Importance

Public health vaccination recommendations for COVID-19 primary series and boosters in previously infected individuals differ worldwide. As infection with SARS-CoV-2 is often asymptomatic, it remains to be determined if vaccine immunogenicity is comparable in all previously infected subjects. We present detailed immunological evidence to clarify the requirements for one-or two-dose primary vaccination series for naturally primed individuals.

Objective

Evaluate the immune response to COVID-19 mRNA vaccines in healthcare workers (HCWs) who recovered from a SARS-CoV-2 infection.

Design

Multicentric observational prospective cohort study of HCWs with a PCR-confirmed SARS-CoV-2 infection designed to evaluate the dynamics of T and B cells immune responses to primary infection and COVID-19 mRNA vaccination over 12 months.

Participants

Unvaccinated HCWs with PCR-confirmed SARS-CoV-2 infection were selected based on the presence or absence of symptoms at infection and serostatus at enrollment. Age- and sex-matched adults not infected with SARS-CoV-2 prior to vaccination were included as naïve controls.

Exposure

Vaccination with Pfizer BioNTech BNT162b2 mRNA vaccine.

Main Outcome(s) and Measure(s)

Immunity score (zero to three), before and after vaccination, based on anti-RBD IgG ratio, serum capacity to neutralize live virus and IFN-γ secretion capacity in response to SARS-CoV-2 peptide pools above the positivity threshold for each of the three assays. We compared the immunity score between groups based on subjects’ symptoms at diagnosis and/or serostatus prior to vaccination.

Results

None of the naïve participants (n=14) showed a maximal immunity score of three following one dose of vaccine compared to 84% of the previously infected participants (n=55). All recovered individuals who did not have an immunity score of three were seronegative prior to vaccination, and 67% had not reported symptoms resulting from their initial infection. Following one dose of vaccine, their immune responses were comparable to naïve individuals, with significantly weaker responses than those who were symptomatic during infection.

Conclusions and Relevance

Individuals who did not develop symptoms during their initial SARS-CoV-2 infection and were seronegative prior to vaccination present immune responses comparable to that of naïve individuals. These findings highlight the importance of administering the complete two-dose primary regimen and following boosters of mRNA vaccines to individuals who experienced asymptomatic SARS-CoV-2 infection.

KEY POINTS

Question

Is a single dose of COVID-19 mRNA vaccine sufficient to induce robust immune responses in individuals with prior SARS-CoV-2 infection?

Findings

In this cohort of 55 health care workers previously infected with SARS-CoV-2, we show that the absence of symptoms during initial infection and negative serostatus prior to vaccination predict the strength of immune responses to COVID-19 mRNA vaccine. Lack of symptoms and a negative serostatus prior to vaccination leads to immune responses comparable to naïve individuals.

Meaning

Our results support a two-dose primary series requirement for any individual with prior history of asymptomatic SARS-CoV-2 infection.