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Our COVID-19 Vaccines Are Good – But There’s One Way They Can Be Better

Our COVID-19 Vaccines Are Good – But There’s One Way They Can Be Better

A medical worker holds a vial of AstraZeneca’s COVID-19 vaccine at a vaccination centre in Ronquieres, Belgium, April 6, 2021. Photo: Reuters/Yves Herman/File Photo

Recently, there has been some public chatter on the presumed ‘failure’ of COVID-19 vaccines in some developed countries, like Israel, the US and the UK – where cases of severe disease have been becoming more noticeable among fully vaccinated individuals.

According to a new report from the US Centres for Disease Control and Prevention (CDC), following multiple large public events in Massachusetts, 346 (74%) out of 469 people with COVID-19 were found to have been fully vaccinated. This finding forced the CDC to make a U-turn on its recommendations, and it urged vaccinated people to mask up indoors in places with high spread of the delta variant.

We know that the delta variant of the novel coronavirus is around twice as contagious and induces viral loads 1,000-times more than the ‘original’ strain. It also has a shorter incubation period, as a result of which people infected with this variant test positive sooner after exposure. This variant is also more likely to break through protections afforded by the vaccines, and could cause more severe disease than all other known variants.

There have been studies from the Israeli health ministry on the limited protection that the Pfizer vaccine offers against symptomatic infections of the delta variant. Similarly, a reports from Public Health England stated that two doses of both the Pfizer and AstraZeneca vaccines offer significantly lower protection against symptomatic infections of the delta variant compared to the alpha variant. Pfizer itself has also acknowledged a faster waning of its vaccines’ effects in Israel.

Primary objectives

Most of the world’s existing crop of COVID-19 vaccines offer high protection against severe COVID-19, hospitalisation and deaths. They also offer considerable protection against symptomatic disease, and modest protection against infections and transmission of the disease. Axiomatically, the vaccines contribute little to our fight against the frequent surges of the SARS-CoV-2 virus.

What should our prime objective be: resisting the ongoing outbreak or avoiding hospitalisations and deaths?

The key edifices of public health and virus transmission dynamics tell us that serious disease that requires hospitalisation, and could culminate in death, but that it contributes little to the virus’s transmission in the human population. It also does not significantly impact the virus’s evolution. The main selective force for the latter is transmission. So preventing severe disease and deaths has immense individual benefits – but as such contributes little to ending the pandemic itself.

Another basic lesson is that there are two broad interventions to manage an infectious disease: prevention and therapy. Vaccination is prevention while (antiviral) drugs used to treat and prevent severe illness and death are therapeutic. In the case of a pandemic of a new virus, vaccines should ideally be able to stop the virus’s ongoing transmission through a population. The current generation of COVID-19 vaccines don’t provide significant protection of this form.

The CDC report – marked ‘preliminary’ – stated, based on health reports available at the time of compiling, that SARS-CoV-2 can thrive in the airways of vaccinated people even if they are asymptomatic. It also reported no difference in the amount of viral particles present in the nasopharynx of a fully vaccinated individual and an unvaccinated individual.

Today, we know that we need vaccines that can provide sterilising immunity – immunity that blocks the transmission of the virus from one vaccinated person to another vaccinated or unvaccinated person.

Even the WHO erred in focusing the primary endpoints of the COVID-19 vaccine trials on preventing symptomatic disease instead of preventing asymptomatic disease and transmission by vaccinated people.

Assessing the efficacy of a vaccine is complex for many diseases, but particularly so in the case of COVID-19, where our fundamental understanding of the pathogen is also evolving. The potential endpoints of an efficacious vaccine include reduction of infection in an individual, mitigation of disease severity or reduction of transmission within a population.

In September 2020, the WHO made at least 50% efficacy against symptomatic disease the essential primary endpoint and clubbed the impact of immunisation on rates of onward transmission under vaccination’s indirect effects. In the case of stable, endemic diseases like hepatitis A and B and chickenpox, individual protection alone can be justified – but amid a fierce pandemic of a new pathogen, the impact of vaccines on transmission dynamics of the virus must take precedence.

Why did WHO overlook the impact of vaccines on transmission? There are a few possibilities. First, the WHO was probably not confident about the success of a new vaccine against a new coronavirus (there are no licensed vaccines for SARS-1 and MERS). Second, the WHO could have determined protection against severe disease to be more important since no effective therapeutic intervention was available. Third, it is much more labour-intensive to detect and capture asymptomatic infections with serial sampling (like weekly swabbing exercises) than to identify symptomatic illness in a vaccine recipient.

However, vaccines that do not much affect the clinical course but reduce the transmissibility of SARS-CoV-2 could still be a very valuable intervention at the population level.

Can’t vaccinate our way out

One of the key objectives of large-scale vaccination is, or was, to achieve herd immunity against the pathogen. But we won’t be able to do this with the vaccines we have access to. Until quite recently, experts advanced 70% vaccination coverage as the herd immunity threshold. It is now likely to be much higher.

The standard calculation for the herd immunity threshold is (1/E) × (1 – 1/Ro). E is the vaccine’s effectiveness at reducing transmission and Ro is the basic reproductive ratio. If Ro is high – 5-9.5 with the delta variant in the US1; let’s assume 6 – and vaccines are 85% effective at preventing transmission, say, we will need to vaccinate 98% of the population. Most nations won’t be able to achieve such high coverage.

But if the vaccines are less effective and the Ro is higher – both likely scenarios around the world – vaccine-induced herd immunity will be impossible. Further, the delta variant is not the last variant to have emerged; there is a real possibility that new strains of even higher transmissibility will turn up, potentially leading to more widespread disease and/or vaccine evasion.

So as things stand, we can’t vaccinate our way out of the pandemic. Instead, to exit the pandemic, we need both vaccines and other non-pharmacological public health measures like masking, social distancing, restrictions on gatherings, etc.

A way out?

To be fair, developing vaccines that can effectively block transmission – i.e. provide sterilising immunity – is a daunting task. We can simplify it to some extent by using a combination of vaccines or by investing in developing a universal coronavirus vaccine (which is scientifically feasible).

For the former, researchers could test the efficacy and safety of a cocktail of mucosal vaccines (intranasal shots that stop the virus at the port of entry), existing parenteral vaccines (to mitigate disease severity), and old live attenuated vaccines (to bolster innate immunity).

Alternatively, a variant-proof universal coronavirus vaccine that is capable of blocking transmission is also eminently doable, but is currently not a priority.

* * *

The novel coronavirus’s evolution signals the importance of rational vaccine design. It isn’t the last pandemic virus either – there are likely to be SARS-CoV-3 and SARS-CoV-4 as well.

So let us invest in developing vaccines that serve the purpose of preventive medicine better, and help halt the transmission of the virus and kill surges, instead of staying limited to preventing severe disease.

Dr Vipin Vashishtha, MD, FIAP, is a consultant paediatrician at the Mangla Hospital and Research Centre, Bijnor.

  1. R0 also depends on local social conditions

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