4th shot of COVID vaccine: Is it worthwhile?

While a fourth dose of the COVID-19 vaccine boosts antibodies to levels that are higher than the third dose, it is not enough to protect against Omicron infections, according to preliminary data from Israel.

Israel was the first country to offer a fourth vaccine dose (ie, 2^nd booster) starting late December 2021 to the vulnerable and high-risk groups, such as the elderly (aged >60 years), immunocompromised patients, and healthcare workers.

Speaking during a press briefing, Professor Gili Regev-Yochay of Sheba Medical Center in Ramat Gan, Israel, who led the booster study in Israel, said “despite a significant increase in antibodies after the fourth vaccine, this protection is only partially effective against the Omicron strain, which is relatively resistant to the vaccine.”  

In the study, 274 healthcare workers who had received the fourth vaccine dose (154 had the Pfizer-BioNTech vaccine 2 weeks earlier and 120 had the Moderna vaccine 1 week earlier, before data collection) were compared to a control group comprising about 6,000 healthcare workers who had yet to receive the fourth shot. All participants were given three doses of the Pfizer-BioNTech vaccine previously.

Although the fourth vaccine dose led to an increase in antibody levels, this was unlikely to be enough to protect against Omicron infection, according to the researchers who have yet to release any specific data from the study. “We know by now that the level of antibodies needed to protect and not to get infected from Omicron is probably too high for the vaccine, even if it's a good vaccine,” said Regev-Yochay.

Preliminary data also indicate that a similar proportion of the twice-boosted participants developed COVID-19 as those who did not receive the fourth vaccine dose, though it is still too early in the trial to tell.

While the percentage appeared slightly lower in participants who had been boosted twice than the control group, the number of Omicron infections was still very high in the former group, Regev-Yochay pointed out.

She did not give further details on how the fourth dose performed against hospitalization or death due to Omicron.

The fourth shots were rolled out in response to early data suggesting that the effectiveness of the initial booster shot (ie, the third vaccine dose) against Omicron infection could wane within 10 weeks, based on preliminary findings from the UK Health Security Agency.

Nonetheless, these early findings do not necessarily mean that the extra booster dose was a futile exercise for some 500,000 Israelis who have received them so far.

The data, however, suggest that it may not be worthwhile to expand the roll-out of the fourth dose to the wider population at large.

Not a sustainable strategy

“A vaccination strategy based on repeated booster doses of the original vaccine composition is unlikely to be appropriate or sustainable,” said the WHO* Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC) in a statement¹.

Instead, the TAG-CO-VAC expert group recommended that the focus should be on developing vaccines that better prevents infection and transmission of emerging variants, in addition to protecting against severe disease and death.

“To that aim, COVID-19 vaccines need to … elicit immune responses that are broad, strong, and long-lasting in order to reduce the need for successive booster doses,” they stressed. “Until such vaccines are available, and as the SARS-CoV-2 virus evolves, the composition of current COVID-19 vaccines may need to be updated.”

The WHO has previously argued against offering blanket booster vaccination in developed nations, when many people in poorer countries have not even  received their very first dose.

“The immediate priority for the world is accelerating access to the primary vaccination, particularly for groups at greater risk of developing severe disease,” they urged, noting that the world will be put at risk of seeing new variants emerging otherwise. 

Questionable approach

The introduction of the fourth booster has drawn flak from the scientific community, some of whom deemed the approach as premature. 

“None of us really understand the scientific basis,” said Professor Saul Faust from the University of Southampton, who is the lead investigator of the Cov-Boost trial studying the impact of booster doses, while giving his opinion in a column for the BMJ. [BMJ 2022;376:o108]

“There is a general feeling among vaccine experts globally that we should wait, especially in the context of such a rapidly evolving Omicron wave,” he commented. “It’s impossible to immunize the entire at-risk global population every 3–4 months, and we can’t predict what the future dominant variant or variants might be.”

Agreeing with the recommendations of the WHO expert group, Faust urged that resources should be prioritized to immunizing as many people who have yet to receive their primary doses as possible, and reserve additional booster doses for the most vulnerable groups.

In addition, developing pan-variant vaccines that tackle vaccine escape would be a more sustainable option in the long term, said Faust, who also leads the phase I trial on DIOSynVax pan-Sarbeco coronavirus vaccine at the University of Cambridge, UK.  

Moving forward

With the sheer rapidity of Omicron’s spread, vaccine developers are not resting on their laurels either. Already, Pfizer/BioNTech and Moderna have been updating their vaccine composition to protect against Omicron, details of which will be released in the coming months.

If the data hold up against Omicron as anticipated, rolling out the updated version of the vaccines would be preferred over repeat boosters with the original vaccine, according to Pfizer CEO Dr Albert Bourla.   

This, perhaps, may bring us one step closer towards a return to normalcy — even if the virus is here to stay.

 

 

*WHO: World Health Organization

¹https://www.who.int/news/item/11-01-2022-interim-statement-on-covid-19-vaccines-in-the-context-of-the-circulation-of-the-omicron-sars-cov-2-variant-from-the-who-technical-advisory-group-on-covid-19-vaccine-composition [Accessed 18 Jan 2022]