International team offers strategy to reduce risk of vaccine-resistant COVID-19 variants

An increase in COVID-19 vaccinations brings with it the risk that a vaccine-resistant strain could still emerge. 

The risk is greatest when only part of a population is vaccinated while a high rate of infection is occurring among the unvaccinated. This is the typical case when a country undertakes a nationwide mass vaccination program. 

The larger the infected group, the more likely it is for a random mutation to occur. If the mutation happens to be vaccine-resistant, it can spread to both vaccinated and unvaccinated. As it now has a larger number of carriers, the tendency will be for this new strain to become the dominant one.

If most of a population could be vaccinated at the same time, it would reduce the risk that a resistant strain could develop and spread––a phenomenon known as “vaccine escape.” 

But in the case of COVID-19, constraints in both manufacturing and distribution, are currently limiting the rate of vaccination worldwide. Further, the relaxation of social distancing measures among the more vaccinated populations adds to the number of infections, increasing the likelihood of a mutation that could be vaccine resistant. 

A team of scientists from China, Israel, and the U.S.A. has developed a sophisticated model for the risk of vaccine escape and proposed a novel way to reduce this risk through a strategy they call spatial vaccination.

The research team consists of lead author Xiyun Zhang of Jinan University (China) and Martin Nowak of Harvard University. Team members from Israel include Gabriel Lobinska and Yitzhak Pilpel of the Weizmann Institute of Science, Michal Feldman, Eddie Dekel, and Ady Pauzner of Tel Aviv University, Yonatan Pauzner of Hayovel Elementary School, and Baruch Barzel of Bar-Ilan University.

The nine-member team explores how focusing COVID-19 vaccination campaigns on a limited geographic areas within a country, and then moving on to contiguous areas, might significantly reduce the risk of vaccine escape and better protect the population as a whole. The team includes mathematical physicists, biologists and epidemiological specialists. 

A preprint of their work was posted on the science website Research Square Oct. 15. (Preprints on the website are preliminary reports on significant topics that have been screened for quality and pseudoscientific claims, but have not yet undergone peer review.) 

Their analysis makes use of the concept of reproduction number (R), which is the estimated number of new cases that an infected person might cause. An R of less than 1 will cause a gradual slowing of disease, as each carrier will infect fewer than one other person. When R rises significantly greater than unity, disease will spread.

Effect of reducing social distancing

The authors note that the “risk of vaccine escape, which exists in any vaccination campaign, is particularly exacerbated by the unique circumstances of COVID-19,” citing numerous studies of the variants and mutations of the SARS CoV-2 virus detected over the last year. 

They note, in particular, that the pandemic has been kept under control by severe social distancing measures, imposed either by government or individual response, but as vaccination uptake increases, there is a gradual relaxation of social distancing measures. “The result, as the short history of this pandemic proves, is an ongoing adaptive behavior that tends to react to the severity of the spread, thus maintaining the effective reproduction number R at around unity.”

“Such a combination of vaccination and adaptive social distancing is unique to the current pandemic,” the authors write, “and may have crucial implications for vaccine escape.” 

Maintaining an R of about 1, as has occurred in the cases of the United Kingdom and the United States, they write, allows for “a significant rate of infection, a rate that will likely persist until vaccination prevalence approaches herd immunity levels.”

“These unique conditions create a potentially fertile breeding ground for vaccine escape," the authors warn.”

The spatial solution

“The straightforward solution,” they note, “is to avoid the extended period in which high vaccination prevalence coexists alongside a high rate of infection.” 

Although the vaccination of the entire population within a short period of time would be ideal, the reality is that vaccination capability is inherently limited.

“To overcome this obstacle, we propose a spatial vaccination strategy which will be shown to dramatically reduce the risk of vaccine escape, even under the existing constraints on the vaccination rate,” the authors write.

The team proposes that national or state governments select regions that are “sufficiently disconnected in terms of social interaction,” and then “sequentially vaccinate one region at a time ... in order to quickly bring that region toward herd immunity.” 

Such a policy need not be in contradiction with a prioritization of the vulnerable population, such as elderly and immune-compromised individuals," they write. "The study examined the effectiveness of beginning a spatial vaccination strategy only after a uniform vaccination of up to 15% of the most vulnerable population nationwide. 

“As we demonstrate, this has limited impact on the outcome of the proposed spatial vaccination strategy,” they note. “The reason is that most of the additional risk of vaccine escape due to uniform vaccination occurs only once vaccine coverage is well above 15%––prior to that the resistant variant’s selective advantage is small.”

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Xiyun Zhang et al. A spatial vaccination strategy to reduce the risk of vaccine-resistant variants, Research Square (2021).

https://doi.org/10.21203/rs.3.rs-969637/v1