Researchers in the United States have proposed changes to the current coronavirus disease 2019 (COVID-19) vaccination strategy that they say would increase the likelihood of herd immunity being achieved in the most timely and cost-effective manner.
The team from the University of Colorado School of Medicine suggests prioritizing the vaccination of individuals who have not already acquired immune protection through previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; the agent that causes COVID-19).
“Unfortunately, until we can safely, rapidly, and affordably vaccinate enough people to achieve collective immunity, we cannot afford to disregard the benefits of naturally acquired immunity in those whose prior documented infections have already run their course,” writes Matin Krsak and colleagues.
The team says that so long as the manufacture, supply, or administration of vaccines is limited, immunizing people with infection-induced immunity at the expense of those without any immune protection is inherently inequitable and violates the principle of justice in biomedical ethics.
Writing in the journal Viral Immunology, Krsak and colleagues say that preventable disease acquired as a result of such unnecessary delay in vaccination should not be overlooked, as it will result in additional morbidity, mortality, and hospitalizations.
“Vaccinating preferentially those without any prior protection will result in fewer natural infections more rapidly,” they add.
Concerns regarding equitable vaccine distribution
Krsak and colleagues say that equitable vaccine distribution will be compromised if the protection afforded to individuals who have already recovered from confirmed symptomatic COVID-19 (csCOVID-19) is not considered.
The team says that worrying assumptions have been made regarding infection- versus vaccine-induced immunity. For example, one assertion is that infection-induced immunity cannot be relied on as this would be ineffective and “lethal to many.”
“In fact, the proportion of individuals with csCOVID-19 reinfection appears to be low,” say the researchers. “Current literature lists only a small number of confirmed and suspected COVID-19 reinfection cases out of over 125 million cases reported by The Johns Hopkins COVID-19 tracker in March 2021.”
The potential advantages of natural infection
Natural infection exposes the immune system to the full set of SARS-CoV-2 antigens, which may confer more protection against variants containing immune escape mutations. This full antigen presentation may also prime a more complete cellular immunity.
Studies have recently reported that coordinated CD4 and CD8 T cell responses to SARS-CoV-2 were strongly associated with milder disease, but the presence of neutralizing antibodies was not.
Furthermore, cellular responses do not appear to be affected by the presence of antibody-escape mutations.
Therefore, cellular immunity may be more important than the antibody response, especially given that some individuals who cleared SARS-CoV-2 infection have been shown to do so in the absence of high or even detectable levels of neutralizing antibodies.
Findings from previous studies
A recent study documenting the incidence of SARS-CoV-2 infection among English healthcare workers found that participants were 89% more likely to be antibody-positive (seropositive) for SARS-CoV-2 than seronegative.
Another study reported that any previous SARS-CoV-2 infection, including the asymptomatic form, would reduce the risk of reinfection by 84% and also reduce the risk of further transmission via convalescents by at least the same amount.
“Within these studies, vaccinating the seropositive healthcare workers would have been the equivalent of revaccinating someone who just got the Oxford/Astra-Zeneca’s ChAdOx1 vaccine in the face of a vaccine shortage,” says Krsak and colleagues.
The researchers say they are skeptical about not considering all individuals who are already naturally protected when allocating the available vaccines.
“If slowing down a rapidly growing pandemic is a solid argument for removing hurdles from the road to collective (herd) immunity, then not wasting time and limited resources on double immunization is part of the solution,” they write.
What does the team propose?
The team proposes the following approach as a way to ensure the equity of vaccine distribution.
1: Conduct mathematical modeling based on the goals and associated prioritization of vaccine allocation as outlined by the Centers for Disease Control and Prevention (CDC) and based on Advisory Committee on Immunization Practices (ACIP) principles. However, also deprioritize individuals with csCOVID-19 for a predefined period of time or until enough vaccines are available.
2: Identify specific vaccines for which efficacy parameters, administration details, projected manufacturing speed and country-specific allocation can all be determined.
3: Use parameters derived from the above two steps to model predictions for achieving CDC/ACIP pre-specified goals and inform any changes needed to improve the performance of vaccine allocations.
4: Ensure that the models account for scenarios where individuals with prior csCOVID-19 would have their vaccination postponed to maximize immunization of all susceptible individuals. This would enable the most time- and cost-effective attainment of population-wide herd immunity, based on incremental vaccine availability.
“Finally, in each modeling iteration, we suggest incorporating projected rates of vaccine refusal in the immediately anticipated vaccination groups based on CDC/ACIP prioritization scheme, as these are currently not insignificant and are likely to influence the attainment of herd immunity,” suggests Krsak and colleagues.
The researchers say that a multi-institutional group of investigators has recently performed similar modeling that incorporated a modified list of parameters.
“Their modeling shows a positive impact on reductions in infections, deaths, and years of life lost when prior seropositivity is accounted for in vaccination strategies,” they write.