Can vaccine evading SARS-CoV-2 variants be restricted by prioritized vaccine rollout?

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to disrupt global public health and economic vitality. In the absence of effective and safe therapeutics, effective vaccination campaigns remain our only hope for a speedy exit.

A new preprint on the medRxiv* server discusses the question of how vaccine priority is affected by the possibility of vaccine escape.

Currently available vaccines

Two vaccines have so far been authorized in the UK, the Pfizer mRNA vaccine and the Oxford-AstraZeneca viral vectored vaccine. These have been reported to have high efficacy against symptomatic infection, with the former claiming up to 94% efficacy.

However, the rapid emergence of SARS-CoV-2 mutants has generated concern among health authorities because of the apparent biological impact of the array of mutations carried by these variants. These effects include increased transmissibility, possibly increased virulence, and partial vaccine resistance.

When vaccines are rolled out on a large scale, positive selection pressure may be exerted on the virus, leading to the emergence of dominant mutations that evade the vaccine-induced immune response. There is inadequate knowledge about these changes at present.

Most countries are deploying vaccines on a priority basis, which in the UK follows the advice of the Joint Committee on Vaccination and Immunization (JCVI). This recommends prioritizing groups at high risk of mortality and healthcare workers.

As evidence of vaccine efficacy came in from the first phase of vaccine rollout, the JCVI updated its advice to recommend age-based prioritization, including the requirement for maximum speed of vaccine deployment.

The current paper uses mathematical modeling to answer the question, using a simplified two-population model with varying rates of susceptibility to the virus and different rates of contact.  

Epidemiological outcomes associated with vaccine coverage

The researchers found that with increasing rates of vaccination, the effective reproduction ratio Re goes down, as long as the vaccine blocks viral transmission to any extent. The correlation between the decrease in the Re and the proportion of the vaccinated population is linear. At the same time, the magnitude of the association increases if people with higher social interactions and less vulnerability (the “mixers”) are vaccinated.

Vaccination reduces severe infections

Severe infections also go down in number over the vaccination period, not only because the Re falls but also because of high coverage among the vulnerable population. This would reduce the number of symptomatic infections more than the number of infections.

Modeling shows that considering the indirect effect of the vaccines on transmission, the optimal plan is seemingly paradoxical. It involves vaccinating the mixers in order to protect the more vulnerable population. This is mostly determined by the fact that the outbreak responds to the vaccine's ability to block viral spread, and somewhat less by the large drop in infections among the mixers with the greatest mixing.

In other words, the aim of vaccination should be to reduce the prevalence of the disease rather than protecting the vulnerable by vaccinating them.

Vaccine escape

Without vaccinating the mixers, but only the vulnerable, the scenario is ripe for vaccine evasion. Conversely, vaccination of the mixers (but not the vulnerable) first boosts the vaccine escape pressure by pushing up the proportion of vaccinated cases, which later drops as more mixers are vaccinated. The absolute number of cases is therefore lower.

What are the implications?

The study has oversimplified many areas, such as dividing the population into only two categories – the vulnerable and the mixers. Again, factors affecting the risk of vaccine escape, such as imported variants, were not implemented. Transmission factors were also represented only by age, excluding household structure, occupation and other relevant factors.

Since several countries have adopted a temporary one-dose vaccine strategy to maximize vaccine coverage and protection during the period of vaccine shortage, it is worth mentioning that this situation is fraught with the risk of viral antigenic adaptation. If the interval between doses is too long, the small decrease in cases in the short term could be more than counterbalanced by the much higher prevalence of infections over the long term, with many more resistant variants.

The vaccine-associated selection pressure may be greatest at intermediate vaccination levels, especially when most of the vulnerable but few of the mixers are covered. This agrees with earlier viral adaptation theories and is also concordant with the earlier reports of the emergence of adaptive, antibody-resistant variants during chronic SARS-CoV-2 infection within immunocompromised hosts.

In defense of this strategy, the one-dose maximal coverage plan envisages significant protection against asymptomatic infection as well. This would markedly reduce the prevalence, and is likely in view of the very high efficacy of the mRNA vaccine reported from phase 1 of the vaccine rollout in the UK.

While this simple model shows the importance of including the aspect of potential vaccine escape from vaccine-induced immunity, along with overall infection burden in a mixed-susceptibility population, more complex modeling will be required to validate these insights in more realistic situations.

*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.

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.