Study shows single dose of mRNA vaccine may suffice for those with prior SARS-CoV-2 infection

A recent study by researchers from Philadelphia, currently available on the medRxiv* preprint server, shows that individuals with prior infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibit substantial immune memory and develop a robust response to the first dose of an mRNA vaccine.

It is established that immune memory resulting from primary infection or vaccine efforts either prevents or weakens the severity of SARS-CoV-2 re-infection and coronavirus disease (COVID-19). And while the exact duration of immunity against the virus remains to be determined, strong humoral and cell-mediated immunity persists for 6-8 months in the majority of infected people.

Hence, vaccines against the SARS-CoV-2 enable rapid and pervasive protective immunity of the uninfected population and, in the long-run, the end of the COVID-19 pandemic. Currently, available mRNA vaccine options utilize the full-length viral spike glycoprotein as the immunogen to generate immune responses greater than those in COVID-19 convalescent sera.

Present recommendations (such as those from the U.S. Centers for Disease Control and Prevention) endorse vaccination for all adults – including those with prior SARS-CoV-2 infection or COVID-19. This is irrespective of the fact that vaccine trials excluded volunteers with a history of COVID-19, the existence of durable immune memory, and extremely low rates of SARS-CoV-2 re-infections.

As the vaccines are still scarce globally, this approach has been recently scrutinized, and it has been implied that individuals with a history of prior SARS-CoV-2 infection should receive only one dose of the vaccine, while the second dose should be postponed for some future date. But is the science strong on this one?

This was the main impetus for conducting this longitudinal study, led by Dr. Steven G. Kelsen from the Lewis Katz School of Medicine at Temple University in Philadelphia, which appraised the immune response to the Pfizer BNT162b2 vaccine in individuals with prior SARS-CoV-2 infection or COVID-19 disease and compared their response to SARS-CoV-2 naïve subjects.

A longitudinal study approach

The subjects in this study were health care workers that were studied longitudinally before and for 56 days after the first dose of the vaccine. This type of study design enabled the assessment of the time course and maximum response of each subject.

Well-established techniques were employed to appraise anti-spike immunoglobulin G (IgG) antibody levels and serum neutralization activity in response to the recommended two-dose regimen of BNT162b2. More specifically, IgG antibodies against the receptor-binding domain (RBD) of the spike glycoprotein were measured, which is the main target of a majority of neutralizing antibodies.

Nonetheless, since antibodies to other epitopes of spike glycoprotein may also have neutralizing activity, this research group has also assessed global humoral immunity to SARS-CoV-2 with the use of a well-accepted, lenti pseudovirus neutralization assay.

Antibody levels and serum neutralizing activity

This study has shown that anti–spike RBD IgG antibody levels and serum neutralizing activity tend to increase more swiftly in individuals with prior SARS-Cov-2 infection or COVID-19 after receiving the Pfizer BNT162b2 vaccine when compared to SARS-CoV-2 naïve subjects.

More specifically, the anti-spike IgG level at day 14 in the COVID-19 group was approximately 15-fold greater, while serum neutralizing activity has been approximately 28-fold greater in comparison to the control group. Moreover, anti-spike antibody and neutralizing activity did not differ between the aforementioned two groups at later time points.

Thereafter, in the COVID-19 cohort, there was a scarce further increase in humoral immunity even after the second dose, such that anti-Spike IgG antibodies and neutralizing activity were quite similar in the two groups from day 28 through day 56

Significant implications for vaccine management

One salient implication of this finding is that individuals with COVID-19 may not necessitate the second dose of the vaccine. Basically, the prior bout of the infection/disease may have resulted in adequate immune stimulation and a near maximal response after the first vaccine dose.

“The possibility that a single dose of vaccine is as efficacious as the two dose regimen in achieving immune protection in subjects with prior SARS-CoV-2 infection / COVID-19 has important public health implications, as it allows conserving approximately 30 million doses in the US alone which could be used for others”, say study authors in this medRxiv paper.

“This issue, however, will require a properly controlled trial in SAR-CoV-2-infected individuals in which the protection against re-infection and COVID-19 achieved with one vaccine dose is compared with the current two-dose regimen”, they add.

In conclusion, this paper implies that subjects with a prior history of (frequently) mild COVID-19 respond more quickly to a COVID-19 mRNA vaccine, achieving a much higher level of humoral immunity after a single dose compared to SARS-CoV-2 naïve individuals. This is a rather important public health finding in terms of ongoing vaccine management.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Dr. Tomislav Meštrović

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university - University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.


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