As the virus evolved, our perception of protection conferred by vaccines changed dramatically. From the popular notions of herd immunity and vaccinating our way out of the pandemic, the discussion is now centred around booster doses and the eventuality of living with the virus.

As the virus evolved, our perception of protection conferred by vaccines changed dramatically.

On this day last year (December 11, 2020), Pfizer’s vaccine for COVID-19 was granted an emergency use authorisation, and exactly a week later, Moderna’s vaccine was granted an EUA. On December 30, 2020, AstraZeneca was given an EUA by the UK drug regulatory body. In India, the drug regulator granted a restricted use authorisation to both Covishield and Covaxin on January 3, 2021.

Herd immunity

The discussion for months before and after the vaccines got an EUA was centred around achieving herd immunity — where a large percentage of the population is infected or vaccinated that virus spread in the population is significantly slowed or stopped. Achieving herd immunity was seen as an end goal of the pandemic. It was made to appear that we could vaccinate our way out of the pandemic and get back to normal times. The over 90% efficacy against symptomatic disease by both the mRNA vaccines made that goal of ending the pandemic look simple and straightforward.  

Except for AstraZeneca and Covaxin vaccines, which also tested trial participants for asymptomatic COVID-19, the efficacy of the two mRNA vaccines were based on their ability to prevent symptomatic COVID-19. This despite the fact that about 80% of infections were asymptomatic. That asymptomatically infected people could still spread the virus to others was overlooked.

Besides major issues of vaccine availability in most countries, vaccine hesitancy and approvals being limited to adults in the beginning meant that reaching this desired percentage needed for achieving herd immunity even in countries which had easy access to vaccines would take several months.

While the mRNA vaccines were very effective at preventing symptomatic disease, their ability to protect people from getting infected remained unclear, which posed a problem for achieving herd immunity.

“Herd immunity is only relevant if we have a transmission-blocking vaccine. If we don’t, then the only way to get herd immunity in the population is to give everyone the vaccine,” Shweta Bansal, a mathematical biologist at Georgetown University in Washington DC told Nature.

Vaccine effectiveness study conducted between December 2020 and end-March 2021 in nearly 4,000 health-care and frontline workers in the U.S. showed full vaccination with mRNA vaccines were 90% effective in preventing infections, regardless of symptom status. So, in mid-May, the CDC director said fully vaccinated people need not wear a mask or maintain physical distance while participating in indoor and outdoor activities.

Delta variant changes the calculus

But the emergence of the Delta variant and its ability to cause breakthrough infections even in fully vaccinated people, and such people shedding the virus and infecting others completely changed the calculus.

It not only forced CDC to revise its masking guidelines in end-July, both herd immunity and the idea of vaccinating our way out of the pandemic were off the charts. The discussion around herd immunity died slowly. Scientists soon realised that it is necessary to vaccinate almost everyone. “Expecting the benefit to pass on to the unvaccinated does not seem to be possible with this virus,” epidemiologist Dr. Giridhara Babu of PHFI had earlier told me.

“The narrative of herd immunity and vaccinating one’s way out of the pandemic was flawed from the beginning. Herd immunity does not apply to coronavirus. These viruses cause recurrent infection. Herd immunity applies to viruses such as measles, where immunity is of the sterilising type, and vaccination of a large segment of the population results in suppression of the epidemic,” Dr. Rajeev Jayadevan, Vice Chairman, Research Cell, Kerala State IMA says in an email.

Focus on booster doses

And Pfizer began aggressively making a case for providing booster doses.

Pfizer began raising concerns about waning immunity despite full vaccination based on vaccine effectiveness studies. But the sharply declining protection that Pfizer was referring to was based on neutralising antibodies which shield the vaccinated people from breakthrough infections. While the Delta variant caused more breakthrough infections even in fully vaccinated people, the vaccines still remained highly effective against severe disease, hospitalisation and death.

Continued protection against severe disease, death

According to a December 9 paper published in The New England Journal of Medicine, the effectiveness of Pfizer vaccine against “symptomatic infection was higher than effectiveness against asymptomatic infection but waned similarly. Variant-specific effectiveness waned in the same pattern”. Most importantly, the effectiveness against severe disease and death reached over 96% two months after the second dose and persisted at nearly the same level for six months.

“The only randomised trial on boosters so far that measured disease outcomes was conducted by Pfizer. There was no difference in severe disease between the two- and three-dose groups,” says Dr. Jayadevan. “In fact, there were no hospitalisations in either group in a study involving over 10,100 people, which suggests that severe disease was not occurring in any significant number even in the two-dose group. As expected, the booster group had fewer infections.”

Protection offered by vaccination in previously infected people has been found to be far superior to protection conferred by full vaccination in infection-naïve individuals. A study posted in the preprint server medRxiv, which is yet to be peer-reviewed, found that compared with full vaccination using Pfizer vaccine, immunity gained from infection offered longer lasting and stronger protection against symptomatic disease and hospitalisation caused by the Delta variant.

“There is no evidence on the ground so far that severe disease, hospitalisation or death has been increasing among fully vaccinated people in India,” Dr. Jayadevan says. “However, breakthrough infections have been occurring, the vast majority of which are asymptomatic or mild.”

Protection against Omicron variant

According to WHO, even in the case of the Omicron variant, early data from South Africa suggest that currently available vaccines are “holding up in protection” against severe disease and death. Though the existing vaccines might prove less effective against Omicron, it is “highly unlikely” the Omicron variant would be able to evade vaccine protections altogether, says Dr. Michael Ryan of the WHO.

A December 8 press release from Pfizer said that two doses showed over 25-fold reduction in neutralisation titres against the Omicron variant in people who had received two doses. But importantly, it said it believes that people vaccinated with two doses “may still be protected against severe forms of the disease”.

Rethink on booster shots

Even as the U.S. has approved booster shots for all adults, the WHO called for a moratorium on booster doses till year-end. On December 9, the WHO said people who are immunocompromised or received an inactivated COVID-19 vaccine (like Covaxin) should receive a third dose to protect against waning immunity.

“A third dose is given to complete a vaccination series in selected subgroups to generate adequate immune responses,” Dr. Jayadevan says. “Immunocompromised individuals require a third dose not because of waning immunity, but because two doses might not evoke a robust response in everyone.”

“For the time being we continue to support the need for equity in distribution [of vaccines] and the use of a third dose is only in those who are immunocompromised or people who have received an inactivated vaccine,” SAGE chair Dr. Alejandro Cravioto told Reuters.

Published in The Hindu on December 11, 2021