Wide-scale vaccine distribution is now taking place in the more economically developed countries worldwide, with counties such as the USA and UK having now vaccinated tens of percent of the total population. In contrast, most of the less wealthy nations may have vaccinated a few percent of the population at best, if any. In a paper recently uploaded to the preprint server medRxiv*, researchers investigate the ultimate influence of unequal vaccine distribution by mathematical modeling, revealing the critical role of fair distribution in future coronavirus disease 2019 (COVID-19) containment strategy.
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Vaccine escape mutant SARS-CoV-2 variants
The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants that evade antibodies generated by the current vaccines is a major concern, and several groups around the world have identified increasingly evasion-prone strains towards vaccine-induced antibodies, facilitated by changes to the receptor-binding domain (RBD) and spike protein that the vaccine emulate. Some viruses, such as polio or measles, are very well controlled by vaccines, and escape mutants rarely occur. Influenza, and some evidence indicates coronaviruses also, frequently exhibit immune escape by a process known as antigenic drift, and therefore require regularly updated vaccines.
The group accounted for two primary factors in the mathematical model: population size and distribution. A smaller population allows for fewer replications wherein mutation can occur, while dense pockets of non-immunized individuals will spread disease more efficiently than a more distributed population.
The group utilized mathematical models to simulate two human populations that were either vaccinated or non-vaccinated to varying degrees, and estimate the probability of vaccine escape mutants spreading between groups. In the first model, one group has complete access to the vaccine while the other does not. In the second model, access to the vaccine is varied amongst the groups in either symmetric or asymmetric manner. Escape mutants are assumed to have a selective advantage over wildtype in the population, meaning that the group elected not to model the complete dynamics of escape variant transmission, only the time until the event.
Symmetric and asymmetric vaccination
Within the fully vaccinated group, there will be limited opportunity for escape mutants to arise, as most of the population is immune to the virus and thus cannot harbor it, providing little opportunity for replication and mutation. However, within this group, the selection for escape mutants is strong, as only escape mutants have a chance of spreading through the wild-type-immunized population. Therefore, when mutants do arise, they are likely to spread quickly amongst the population with less competition originating from the wildtype or any other variant that is sensitive to the vaccine-generated antibodies. Alternatively, within the unvaccinated group, there is little selective advantage towards escape mutants, though a high rate of replication in a large number of hosts enhances the probability of mutations arising.
The likelihood of transmission between the groups was set significantly lower than that assumed within the groups in order to represent geographical distance or political borders. In any case, the mathematical model suggested that the emergence of vaccine escape variants in the vaccinated group was around ten times more likely when neighboring an unvaccinated group compared to being isolated. The authors highlight Israel as a similar example of this, which has engaged in an impressive vaccination program that has now immunized the majority of the population, though is surrounded by nations with among the lowest vaccination rates in the world.
Interestingly, moderate asymmetrical disparities in vaccine distribution between the groups could produce more probable vaccine escape mutant generation than complete disparity. When the rate of vaccination was set to around 10-20% and 80-90% between the two groups, respectively, the optimum occurrence of vaccine escape mutants transmitting between groups was observed. Presumably, at these values, each group contains a reservoir of unvaccinated individuals that provide a sufficiently high reproduction rate to enhance mutant occurrence. In contrast, the opposing vaccinated population within the same group acts as a filter that selects for these mutants once they arise. The enhanced intra-group mixing compared with mixing between groups promotes this effect compared with that observed in two completely asymmetrically vaccinated groups, where mixing rarely occurs.
Importantly, equal vaccination between the groups was found to give the lowest probability of vaccine escape mutants.
The mathematical model employed by the group accounted for public policy regarding border closures, mask-wearing, and other social distancing measures. As these policies are steadily alleviated, the group notes that it will be important to monitor the effect on transmission, as the probability of vaccine mutant strain transmission within and between groups is correlated with these values.
The authors suggest that this work provides a theoretical basis for the equal distribution of vaccines. Unvaccinated human subpopulations act as a reservoir for the generation of vaccine escape mutant strains, which when allowed to escape into the vaccinated population prosper very quickly, as no immunity exists. Large asymmetrically vaccinated adjacent populations exacerbate this effect most severely; for example, two nearby cities with an intervening national border, where one nation has good access to vaccines, and the other does not. Containing SARS-CoV-2 at this early stage could prove vital, as if allowed to continuously exist and reproduce in isolated pockets, the poorest nations in particular, it could become endemic, and require continuous vaccine updates and rollouts for the foreseeable future, as with influenza.
*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.
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