The end of the ongoing coronavirus disease 2019 (COVID-19) pandemic may be in sight, with several countries having rolled out vaccination programs against the causative pathogen: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These campaigns aim to induce population immunity rapidly.
A new study by scientists in the UK raises the very useful hypothesis that natural infection may help spread the vaccine thinner without loss of efficacy.
However, as new variants continue to emerge, the importance of early impact is clear in preventing their spread, with associated resistance to earlier antibodies. Current vaccines are generally based on the two-dose approach, with a priming dose followed by a booster.
The elicited antibodies are directed against the viral spike antigen, and their titers are found to be correlated with actual neutralization ability. The antibody titers increase following the administration of a booster.
The researchers considered the hypothesis that prior natural infection could act as a priming dose so that the vaccine boost dose would be simulated by the actual prime dose in such individuals.
The current study uses a cohort of 51 participants, part of the COVIDsortium longitudinal study of health-care workers (HCWs) in London. These workers have been tested weekly by polymerase chain reaction (PCR) for the virus, accompanied by quantitative antibody testing, from March 23, 2020, onwards for 16 weeks.
During this period, 24 of them became infected with SARS-CoV-2 as confirmed by anti-S or anti-N antibodies – against the viral spike or nucleocapsid, respectively. Twenty-seven were seronegative. Peak antibody levels were identified in seropositive individuals due to the longitudinal nature of the study.
All subjects were vaccinated 19-29 days before the first test. The researchers found that in the uninfected seronegative group, the anti-spike antibody titers were similar to the peak titers found after natural infection.
Among those with a history of natural infection followed by one dose of vaccine, the peak anti-S titers were over 140 times greater than without vaccination.
Compared to the peak titers after a prime-boost regimen in SARS-CoV-2-naïve individuals in any previous study, the response is at least one order of magnitude greater.
What are the implications?
The study suggests that for the BNT162b2 mRNA vaccine, naïve and previously infected individuals should be distinguished by serological testing before the first dose is given. Based on these tests, boost doses can be avoided for those with preexisting antibodies to the virus.
The result would be faster coverage of a larger population without impacting the resultant immunity. The eventual outcome would be to reduce the chances of the emergence of vaccine-resistant mutants, such as the already troublesome UK, South African and Brazil variants.
These variants are strongly suspected to be not just more transmissible but potentially more virulent. In addition, the South African variant, at least, has been reported in some studies to confer partial resistance to vaccine-induced neutralizing antibodies.
This protocol would also avoid reactions due to unnecessarily high antibody levels caused by the actual boost dose, which is desirable both on account of the patient’s welfare on an individual level, and because such reactions could promote unwillingness to take the vaccine.
The duration of vaccine-induced immunity among those with a history of prior infection remains to be determined, compared to that caused by a full course of vaccination in the infection-naïve. However, even as it stands, “our findings provide a rationale for serology-based vaccine dosing to maximize coverage and impact.”
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