Credit ACIP/CDC
#16,096
Vaccines are undoubtedly our best tool against the COVID pandemic, but they are not a perfect tool. The CDC estimates thousands of COVID breakthrough infections occur each week in fully vaccinated individuals, and many people remain only partially vaccinated, and therefore vulnerable, particularly to the new Delta variant.
That said, COVID vaccines have saved, and will continue to save, countless lives. They can substantially reduce the burden of illness from the virus, and that should mitigate much of the pandemic's worst impacts on the healthcare delivery system.
But vaccines, particularly when used against highly mutable viruses (like SARS-CoV-2), have the potential to become a double-edged sword. Under the right (or, if you prefer `wrong') conditions, they can help drive viral evolution, which can lead to vaccine-escape variants.
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.
Simply put, 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.
Since this study was published, we have seen a highly effective poultry vaccination program in China, launched in 2017, that - so far at least - has kept avian H7N9 at bay, and greatly reduced HPAI H5N6 (see EID Journal: China's H5+H7 Poultry Vaccination Program, Guangdong 2017-18).
But vaccine-driven evolution - particularly in partially vaccinated hosts, or among vaccine breakthrough cases - can occur. This isn't the only way a vaccine resistant variant may emerge (see below), but it is certainly one of the ways.
Yesterday, in UK SAGE: Can We Predict the Limits of SARS-CoV-2 Variants and their Phenotypic Consequences?), the authors stated that seeing an emerging variant that evades current vaccines due to recombination or reverse zoonosis is a realistic possibility, and call genetic and antigenic drift almost inevitable.
While we shouldn't let the want of perfect tool get in the way of using a good tool, we do need to be aware that vaccine-escape variants could arise because vaccines are incapable of preventing infection 100% of the time.
All of which leads us into another SAGE report, also published on Friday, that looks at the potential impact of vaccine-induced viral evolution of SARS-CoV-2. While they argue that increased international vaccine coverage is more likely to help prevent the emergence of new variants, they acknowledge there are unknowns.
I've included the Executive summary, and a few excerpts, but you'll want to download and read the full 10-page PDF. I'll have a brief postscript when you return.
International vaccination: Potential impact on viral evolution andUK public health
Contributors (in alphabetical order): Samuel Clifford, Rosalind Eggo, Julia Gog, Bryan Grenfell, Deirdre Hollingsworth, Petra Klepac, Jessica Metcalf, Billy Quilty, and Robin Thompson.
This paper summarises the current scientific consensus and hypothesis on the role of global vaccination in emergence and importation of new variants, and identifies key areas of uncertainty for making future projections and policies. We highlight key considerations for future policymaking, and where that could be guided by new evidence. Some aspects relate to medium-term decisions (~3 months) and others to long-term issues (~12 months) as travel and behaviour returns to baseline.
Executive summary
Context
● The biggest threat to the UK’s health security and response to the SARS-CoV-2 pandemic is the emergence (and establishment within the UK) of variants that either have increased transmissibility, increased disease severity, escape prior immunity, or a combination of these characteristics [high confidence]
● Substantial global circulation of SARS-CoV-2 will lead to the evolution of new variants and continued risk of importation to the UK [medium confidence].
● Increased international vaccination by donation/sharing of purchased doses, or supporting increased manufacture, has the potential to reduce the appearance and establishment of variants internationally, as well as the risk of their importation to the UK [medium confidence].
Evolutionary considerations
● It is unknown how levels of vaccination change the relative risk of the appearance and establishment of an immune escape variant. Most current variants of concern emerged before mass vaccination or high population immunity from infection [medium confidence]. Any level of population immunity may increase selection pressure for immune escape variants but there is no evidence to suggest this pressure would be greater for vaccine-induced immunity than immunity driven by infection [medium confidence].
● At the individual level, partial immunity may create conditions that favour onward transmission of variants with immune escape-associated mutations [low confidence]. However, it is not yet clear how different vaccines, dosing regimes, or immunity from previous infection may intersect with different variants and individual host characteristics to influence the emergence of immune escape variants [medium-high confidence].
● If immunocompromised or populations otherwise vulnerable to chronic infections are shown to be a significant source of new variants with concerning characteristics, then focussing global vaccination efforts to these populations (and their contacts) may reduce the risk of new variants of concern emerging [medium-high confidence].
Risk of importation of novel variants
● As the number of travellers to the UK increases so will the risk of importation of variants and the burden on genomic surveillance systems [high confidence]. The number of importations that would result in the establishment of local transmission of a new variant is difficult to predict due to overdispersion and the unpredictability of variant characteristics such as transmissibility [high confidence]. Border measures are likely to delay but not prevent introduction [high confidence].
● If vaccination continues to protect against infection, and reduce onward transmission, then requiring travellers to be vaccinated is likely to reduce the risk of importation but may exacerbate inequalities if international vaccination coverage remains low and heterogenous [high confidence].
● Imported cases are less likely to lead to outbreaks and established community transmission in the UK if transmission in the UK is controlled, by population immunity or non-pharmaceutical interventions [high confidence].
● It is unclear which domestic communities may be at higher risk from imported variants. Increasing domestic vaccination in all groups or those with higher exposure to international travellers is likely to reduce the probability of establishment of transmission after importation [high confidence].
Benefits of international vaccination
● A successful domestic strategy hinges on achieving low numbers of infections globally to reduce the emergence of novel variants of concern [medium-high confidence].
● Establishing the optimal priority or targeting of international vaccination efforts is complicated by biological uncertainties and logistical complexities (e.g. distribution, vaccine hesitancy, regional stability, etc). In the short term, prioritisation of countries with higher volumes of travellers coming to or from the UK (or for whom more open borders are economically desirable) could be considered [low confidence].
● Multilateral cooperation and a commitment to increasing global vaccination rates, in part by sharing resources such as doses, is highly likely to have the biggest impact on the incidence of infections globally and thus the biggest impact on the risk of the emergence of new variants [medium-high confidence].
1. Introduction
The biggest threat to the UK’s health security and response to the SARS-CoV-2 pandemic in the medium to long term is the emergence (and establishment within the UK) of variants which have any of the properties of:
a. increased transmissibility (or faster growth through any means)
b. higher severity (causing worse health outcomes)
c. escape prior immunity (from previous infection or vaccine)
d. any combinations of the above.
The steps on the pathway from international emergence to establishment of domestic transmission in the UK on which interventions can act:
a. A variant first appears through mutation in the unknown source location
b. The variant establishes transmission in that location note: (emergence: both a and b together)
c. The variant is imported to the UK
d. Establishment of transmission of the variant in the UK.
Increased international vaccination by donation or sharing of doses or supporting manufacture, has the potential to reduce the risks of the first three steps, hence reducing the threat to the UK.
In this paper, we explore the evolutionary arguments for the effects of vaccination, consider in more detail international importation routes, and combine these to draw out consequences for a successful strategy for the UK for international vaccination. Finally we highlight the key unknowns, and areas where further work is urgently needed.
While it is true that vaccines may help drive viral evolution, most of the variants we are dealing with today appeared long before vaccines were deployed on a large scale. SARS-CoV-2 has demonstrated its ability to evolve without our help, and so any added risk of seeing vaccine-escape mutations seems more than offset by the benefits of mass vaccination.
But as a practical matter, the vaccines we have today will periodically need to be updated if they are to keep up with an ever evolving coronavirus.
There are no foolproof battleplans for this (or any) pandemic. Global public health outbreaks are complicated and messy, and our responses to them are often confused or suboptimal. While science should guide us, it doesn't always give us definitive answers at the moment we need them.
In those cases, the best we can do is pick what appears to be the right course at the time, and be ready to pivot if things don't go as planned. 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.
