#17,071
While COVID vaccines have saved millions of lives, and spared countless more from severe illness, one of the theoretical concerns over the deployment of any pandemic vaccine - particularly when used against highly mutable viruses - is that they can help drive viral evolution, leading to the generation of vaccine-escape variants.
This is a phenomenon we've examined previously with poultry vaccines used to prevent avian influenza. The following comes from a 2014 EID Journal dispatch titled Subclinical Highly Pathogenic Avian Influenza Virus Infection among Vaccinated Chickens, China:
HPAI mass vaccination played a crucial role in HPAI control in China. However, this study demonstrated multiple disadvantages of HPAI mass vaccination, which had been suspected (13,14). For example, this study showed that H5N1 subtype HPAI virus has evolved into multiple H5N2 genotypes, which are all likely vaccine-escape variants, suggesting that this virus can easily evolve into vaccine-escape variants.
This observation suggests that HPAI mass vaccination, which is highly effective in the beginning of an outbreak, may lose its effectiveness with time unless the vaccine strains are updated. Moreover, this study showed that vaccinated chicken flocks can be infected with vaccine-escape variants without signs of illness.
The reality is, vaccines don’t always prevent infection. Sometimes they only mask or minimize the symptoms, and in that environment vaccine resistant mutations may emerge and potentially be transmitted onward.
It is also a topic we looked at 14 months ago (see UK Sage: International Vaccination: Potential impact on Viral Evolution and UK), in a report that looked at the potential impact of vaccine-induced viral evolution of SARS-CoV-2.
While the authors argued that increased international vaccine coverage is more likely to help prevent the emergence of new variants, they acknowledged there were unknowns.
Since SARS-CoV-2 virus was evolving rapidly long before a vaccine was released, it is of little surprise that a year later we find ourselves with significantly reduced vaccine effectiveness due to the emergence of multiple Omicron variants.
Over the summer of 2021, in UK SAGE: Can We Predict the Limits of SARS-CoV-2 Variants and their Phenotypic Consequences?), the group called additional genetic and antigenic drift of the virus almost inevitable.But the question remains: Did the vaccine contribute to this abrupt evolutionary shift in the virus?
With the caveat that there are limits as to what can be deduced from the data available, we have a study - published in the Journal Viruses - which finds little evidence that high vaccine uptake is driving the evolution of the SARS-CoV-2 virus.
This is a lengthy, detailed, and at times highly technical paper. I've only posted the abstract and an excerpt from the Discussion, so those with a high tolerance for statistical analysis will want to follow the link to read it in its entirety.
I'll have a brief postscript when you return.
Evolutionary Pattern Comparisons of the SARS-CoV-2 Delta Variant in Countries/Regions with High and Low Vaccine Coverage
by
Jiahao Zhang †, Linqian Fan †, Hanli Xu, Yuanhui Fu, Xianglei Peng, Yanpeng Zheng, Jiemei Yu * and
Jinsheng He *
College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing 100044, China
Abstract
It has been argued that vaccine-breakthrough infections of SARS-CoV-2 would likely accelerate the emergence of novel variants with immune evasion. This study explored the evolutionary patterns of the Delta variant in countries/regions with relatively high and low vaccine coverage based on large-scale sequences.
Our results showed that (i) the sequences were grouped into two clusters (L and R); the R cluster was dominant, its proportion increased over time and was higher in the high-vaccine-coverage areas; (ii) genetic diversities in the countries/regions with low vaccine coverage were higher than those in the ones with high vaccine coverage; (iii) unique mutations and co-mutations were detected in different countries/regions; in particular, common co-mutations were exhibited in highly occurring frequencies in the areas with high vaccine coverage and presented in increasing frequencies over time in the areas with low vaccine coverage; (iv) five sites on the S protein were under strong positive selection in different countries/regions, with three in non-C to U sites (I95T, G142D and T950N), and the occurring frequencies of I95T in high vaccine coverage areas were higher, while G142D and T950N were potentially immune-pressure-selected sites; and (v) mutation at the N6-methyladenosine site 4 on ORF7a (C27527T, P45L) was detected and might be caused by immune pressure.
Our study suggested that certain variation differences existed between countries/regions with high and low vaccine coverage, but they were not likely caused by host immune pressure. We inferred that no extra immune pressures on SARS-CoV-2 were generated with high vaccine coverage, and we suggest promoting and strengthening the uptake of the COVID-19 vaccine worldwide, especially in less developed areas.
(SNIP)
In conclusion, this study suggested that greater genetic diversities were found in the areas with low vaccine coverage than those with high vaccine coverage, which may promote the ongoing emergence of variants of concern; though specific mutations and co-mutations with highly occurring frequencies were detected in different countries/areas, none were located in the RBD, and we could not rule out the possibility that the differences may resulted from the founder effect or other factors, such as population background.
Of course, although the vaccine coverage in India and Africa was low, their natural infection rates were not, especially in India; here we cannot distinguish the difference in immunity caused by natural infection and vaccination. However, we can infer that high vaccine coverage would not cause extra immune pressure on the virus, which proved the speculation in a previous study that in SARS-CoV-2 infection, vaccine-derived immunity was unlikely to cause selective pressure for immune escape [51].Due to the limitation of sequencing capacity and the imbalance of regional economic development, and limited areas included in this study, as well as the unclear information on vaccine type and detailed distribution, the conclusions obtained in this study may be biased. Nevertheless, we suggest promoting and strengthening vaccination through increasing COVID-19 vaccine confidence and supply in less developed countries.
While reassuring, this study has a number of limitations. But it falls in line with others we've seen, which find that the benefits of mass vaccination against COVID vastly outweigh the potential risks.
Like it or not, there are no foolproof battle plans for this (or any) pandemic. Global public health outbreaks are complicated and messy, and our responses to them are often confused, sub-optimal, or flawed.
While science should guide us, it can't always provide us the answers we need at the moment we need them.
The best we can do is pick what appears to be the right course at the time, and be ready to pivot if things go badly. Not everything we will try will work. Some may even backfire.
But in a pandemic - as in any crisis - we can't let the fear of failure paralyze us into doing nothing.
