Omicron: How well do COVID-19 boosters protect against it?

With the latest surge of COVID-19 cases sweeping across the world, countries have been stepping up on their booster vaccination programme to curb the spread of COVID-19.

The rise in COVID-19 cases occurred despite high vaccination rate with two primary doses of vaccines, such as that seen in Israel — the cause of which experts believed to be the higher infectiousness of emerging variants of concern including Delta and Omicron, coupled with waning immunity over time from previous vaccination.

In a case-control study involving 306,710 adults aged ≥40 years (55 percent female) in Israel, 6.6 percent of the participants who received only two doses of the BNT162b2 mRNA vaccine tested positive on PCR for SARS-CoV-2 compared with only 1.8 percent positive cases among those who had received a booster shot after their primary vaccine course. [JAMA Intern Med 2021;doi:10.1001/jamainternmed.2021.7382]

This translates to about 86 percent lower odds of testing positive for SARS-CoV-2 (estimated odds ratio, 0.14, 95 percent confidence interval [CI], 0.13–0.15) at 28–65 days after receiving booster compared with only two primary doses of vaccine. 

“The findings of this study suggest that the waning of vaccine-induced protection against SARS-CoV-2 infection seems to be counteracted in the short-term by a third dose and further monitoring is needed to determine the duration of immunity following the booster,” said the researchers.

Similar findings were seen in two other real-world studies in Israel involving participants of different age groups. The first study, which involved 1,137,804 participants aged ≥60 years, showed that boosters reduced the rate of confirmed infection by a factor of 11.3 and the rate of severe illness by a factor of 19.5 than those fully vaccinated but had not received a booster. [N Engl J Med 2021;385:1393-1400]

Consistent with this, the second study found that the additional protection with booster extends to the general population as well (728,321 participants aged ≥12 years; median age 52 years). When assessed ≥7 days after receiving a booster, the estimated vaccine effectiveness was 93 percent against hospitalization, 92 percent against severe disease, and 81 percent against COVID-19-related death, compared with those who were fully vaccinated at least 5 months ago but had yet to take a booster shot. [Lancet 2021;398:2093–2100]

How about protection against Omicron?

Preliminary laboratory data released by Pfizer recently indicate that getting a booster shot of the BNT162b2 vaccine substantially increased the neutralizing antibody titres by 25-fold relative to only two primary doses of the vaccine, against the Omicron variant.

The neutralizing antibody titres induced by boosters were as high as that seen after two primary doses against the wild-type coronavirus.

By contrast, people who received only two primary doses of the BNT162b2 vaccine had significantly reduced neutralization titres against the Omicron variant.

Nonetheless, the researchers pointed out that two doses of vaccine may still protect against severe disease to some extent, as 80 percent of epitopes in the viral spike protein targeted by the human immune CD8+ T cells were not mutated in the Omicron variant. However, a third dose induced a much robust immune response and would greatly enhance the protection in the face of Omicron. 

Besides an enhanced neutralizing antibody response, the third vaccine dose also induced strong CD8+ T-cell response against multiple epitopes of the viral spike protein — which has been correlated with protection against severe COVID-19 disease.

“Although two doses of the vaccine may still offer protection against severe disease caused by the Omicron strain, it’s clear from these preliminary data that protection is improved with a third dose of our vaccine,” said Pfizer CEO Albert Bourla in  a company statement.  

“Ensuring as many people as possible are fully vaccinated with the first two-dose series and a booster remains the best course of action to prevent the spread of COVID-19,” he highlighted.

Similarly, Moderna’s mRNA-1273 vaccine enhanced neutralizing antibody levels by 37-fold against Omicron at the 50 µg booster dose compared with preboost levels, based on preliminary data from an ongoing phase II/III study.

Even so, how long does it last?

While findings suggest that boosters do provide protection against the Omicron variant, the durability of such protection remains uncertain.

A new report UK Health Security Agency offers a glimpse into how long the protection against Omicron might last with the boosters.  

Based on data from 68,489 Omicron cases in the UK, researchers found that while both the BNT162b2 and mRNA-1273 vaccines offered approximately 70 percent effectiveness against symptomatic disease caused by Omicron at 2-4 weeks after a booster shot, immune response appeared to wane faster after the BNT162b2 booster than the mRNA-1273 counterpart.

With the BNT162b2 boosters, the protection against Omicron plunged to 45 percent after 10 weeks, whereas this remained relatively stable at around 70 percent with the mRNA-1273 boosters for at least 9 weeks.