Single-dose of BNT162b2 vaccine may not be protective without prior SARS-CoV-2 infection

Vaccine rollouts in many countries are bringing hope that the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), will come to an end in the foreseeable future. Several vaccines have shown high protective efficacy against SARS-CoV-2 infection or severe disease.

A new study by researchers at Imperial College London, UK, discusses the effect of a vaccine dose, specifically the BNT162b2 candidate (also known as the ‘Pfizer-BioNTech’ vaccine), on neutralizing antibody titers in individuals who have already been infected with the virus.

Single-dose regimen

The UK government has already vaccinated many healthcare workers (HCWs) and other front-line workers with the BNT162b2 mRNA vaccine. To expand coverage and contain the spike in cases, the interval between vaccine doses has been increased to 12 weeks.

Not much information is available on the results of single-dose vaccination. Moreover, the nature of responses to vaccination following natural infection remains unclear. The current study explores the serology, neutralizing responses and T cell responses to a single dose of BNT162b2 mRNA vaccine.

The study includes 72 HCWs who were vaccinated in the same week. The BNT162b2 mRNA encodes the spike antigen of the virus.

Infected prior to vaccination

Baseline blood samples at the time of their first dose showed antibodies to the viral nucleocapsid and spike (anti-S) proteins in 16 patients. Another five patients had strong T cell reactivity to non-spike viral antigens after vaccination and were also considered to have had prior viral exposure.

The immune response in this group did not show any correlation with age.

The remaining 51 participants were negative for immune responses to the virus and were called infection-naïve.

Higher antibody to spike after vaccination

After one dose of the vaccine, the participants showed markedly higher antibodies to the spike antigen if they had a history of natural infection compared to the naïve individuals. The median anti-spike titer was ~16,000 AU/mL in the first group, versus ~600 AU/mL in the second, indicating an almost 30-fold difference.

The five participants with isolated T cell responses had spike antibody responses following vaccination that was somewhere between the seropositive group and the naïve group.

The naïve group developed antibody titers inversely correlated with age. Those above 50 years had a substantially weaker response to the vaccine compared with younger participants, at a median of ~200 AU/mL, versus 900 AU/mL.

Live virus neutralization

To examine the neutralizing capacity of the vaccine-induced antibodies, the researchers tested four samples each from the infected and naïve groups, before vaccination, for liver virus neutralization on Vero cells.

Another post-vaccination sample set was also tested at 12 naïve versus three infected samples.

The researchers found very strong neutralizing responses had been induced in those with previous exposure, even in those whose baseline neutralization titers had been undetectable or very low.

In contrast, naïve individuals showed neutralizing activity in 15/16 sera, but with much lower titers. The 50% neutralization titers, NT50, showed a twenty-fold difference, at 1/30 for this group, compared to 1/1,600 for the infected group.

T cell responses

The study also examined T cell responses following vaccination using enzyme-linked immune absorbent spot (ELISpot) against a set of five viral peptide pools. They found very strong T cell responses to the spike peptides in the previously infected subjects following vaccination, at over ten-fold the median responses in naïve individuals.

In fact, about half of the 48 participants in this part of the study had negative T cell responses. There was no correlation between age and T cell response.

Thus, a single dose of the BNT162b2 vaccine appears to create strong humoral and cellular responses in individuals who have already been infected with SARS-CoV-2, associated with high live virus neutralizing capacity. Both neutralizing antibody and T cell responses are weak, in contrast, among the infection-naïve group, following one dose.

What are the implications?

The study shows that robust immunity is generated following vaccination in people with a history of prior infection. On the contrary, a proportion of previously uninfected people show very poor responses to the vaccine, hinting that both clinical disease and viral shedding might occur in this subset.

Moreover, the immunity level may be too low to persist for the newly determined 12-week interval until the second dose. Anecdotally, it may be observed that one such individual developed clinical disease, confirmed by polymerase chain reaction (PCR), at five weeks from the first dose of vaccine, with the anti-spike antibody titer after vaccination being 60 AU/mL.

The age-dependent decrease in vaccine-elicited immune responses seen in the infection-naïve group is an obvious concern. Of the group of ten who were older than 50, seroconversion did not occur, and eight had low antibody titers below 250 AU/mL, insufficient for neutralization as judged by the relationship between anti-S antibody levels and virus neutralization in the current assay.

Not only is this group at higher risk of severe disease, but they show a minimal vaccine response, according to these findings.

This may indicate the need to prioritize infection-naïve individuals and those over 50 years for a complete vaccination regimen. Additionally, it emphasizes the need to be alert even after vaccination, including the use of personal protective equipment as before, to avoid either contracting infection or spreading the virus via asymptomatic viral shedding.

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.