3 COVID vaccine doses appear to protect against Omicron subvariants

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Center for Infectious Disease Research and Policy

Mary Van Beusekom | News Writer | CIDRAP News.

Three new studies report on COVID-19 vaccine effectiveness (VE) and antibody responses to Omicron, with one from Sweden finding a drop in two-dose VE against severe disease after the transition from the BA.1 to the BA.2 subvariant but three-dose protection remaining above 80% against severe disease.

Also, a study from Hong Kong shows good antibody response against BA.2 after three doses, and one from the United States finds that nursing home patients who received a third dose had a 47% lower risk of Omicron infection.

Three-dose vaccine efficacy above 80%

A team led by a Skane University Hospital researcher conducted a vaccine-registry COVID-19 surveillance study of all 1,384,531 residents of a county in southern Sweden from Dec 27, 2020, when the COVID-19 vaccine rollout began in that country, to Mar 15, 2022. The findings were published yesterday in Eurosurveillance.

Most doses (77%) were of the Pfizer/BioNTech COVID-19 vaccine, with Moderna and AstraZeneca/Oxford making up the remaining doses.

The study spanned three periods: week 52 of 2021 to week 1 of 2022, in which Omicron BA.1 was dominant (60% vs 25% Delta and 15% BA.2); weeks 2 and 3 of 2022, the transition period (BA.1 [47%], Delta [4.5%], and BA.2 [49%]); and weeks 4 to 11 of 2022, when BA.2 was dominant (82% vs 17% BA.1 and 0.5% Delta).

A total of 593 severe COVID-19 infections occurred, corresponding to 65, 78, and 56 cases each week during BA.1 dominance, the transition period, and BA.2, respectively. Relative to the BA.1 period, during the BA.2 period, patients with severe illness were older and had a more even sex distribution. The overrepresentation of patients born outside of Sweden during BA.1 lessened during BA.2, but these patients had a similar prevalence of chronic conditions.

Estimated VE of two doses against severe COVID-19 was 89% from March to November 2021, before follow-up began. Population-level protection remained high during Delta and BA.1 dominance in December 2021, while VE declined during the transition to BA.2 in January and February 2022.

After at least three doses, VE against severe disease remained above 80% throughout the study period but fell from 90% during BA.1 to 54% during BA.2 in two-dose recipients, regardless of age, sex, and chronic conditions.

Previous SARS-CoV-2 infection offered comparable protection against reinfection after two or three vaccine doses during BA.1 and the transition period, but the protection conferred by infection and at most two doses dropped during BA.2, while the protection against severe illness conferred by least three doses remained high.

The key finding, the researchers said, was the steep decline in estimated VE against severe COVID-19 during BA.2 dominance in two-dose vaccine recipients.

“The decline occurred quite rapidly over two months and thus cannot be explained by waning VE alone,” they wrote. “A more likely explanation is increased immune evasiveness properties of BA.2, which gives this genetically distinct subvariant a competitive advantage in highly vaccinated populations.”

“The relatively stable protection among individuals with at least three doses during follow-up in our study suggests that a very robust immune response is necessary to confer protection also against BA.2,” the researchers added. “These findings from our population-based study suggest that booster vaccination is needed to maintain sufficient protection against severe COVID-19.”

Lower antibody responses in unvaccinated BA.2 patients

A second study published in Eurosurveillance, led by University of Hong Kong researchers, involved a randomly chosen subset of 20 participants from a previous study comparing levels of plaque reduction neutralization test (PRNT) antibodies against the wild-type and BA.1 SARS-CoV-2 variants. The study spanned Feb 21, 2020, to Nov 20, 2021.

Participants included those who were never infected with COVID-19 and were vaccinated with three doses of the Pfizer or CoronaVac vaccine, as well as those who received two doses of CoronaVac and one dose of Pfizer.

Unvaccinated participants infected with the wild-type virus 143 to 196 days earlier had waning antibody concentrations in recovery. Serum was collected 3 to 5 weeks after the last dose of vaccine.

The researchers also collected and sequenced serum samples from survivors of BA.1 infections (14 patients) and presumed BA.2 (27) infections that occurred after Jan 21, 2022, when BA.2 was dominant. All BA.1-infected participants and 20 infected with BA.2 were reinfected.  Among the 34 reinfected patients, 22 had been vaccinated with Pfizer, while 9 had received CoronaVac, and 1 each had received AstraZeneca, Moderna, and a combination of Pfizer and Johnson & Johnson (J&J).

Three doses of the Pfizer COVID-19 vaccine seemed to elicit greater PRNT antibody response against BA.1 than three doses of CoronaVac. In both vaccinated participants and those diagnosed as having COVID-19 wild-type infection with or without vaccination, PRNT antibody responses to BA.2 were significantly lower than those against the wild-type virus, but PRNT antibody responses to BA.1 and BA.2 were similar. BA.2 infections in unvaccinated participants resulted in low PRNT antibody levels against BA.2, which were 2- to 16-fold higher than those to BA.1.

The study authors noted that there is no universally accepted correlate of protection against COVID-19. “A single dose of either vaccine in those with previous SARS-CoV-2 infection elicited higher PRNT antibody responses than even three doses of the respective vaccine in infection naïve individuals,” they wrote. “Breakthrough BA.1 or BA.2 infection in previously vaccinated individuals appeared to provide broad cross-neutralisation against a range of SARS-CoV-2 variants of concern.”

“In contrast, BA.2 infection in non-vaccinated individuals provided low PRNT antibody responses to BA.2 with minimal breadth of cross-neutralisation and they may be susceptible to infection with BA.1 or other variants,” the researchers added.

Additional doses in nursing homes

In the third study, published today in Morbidity and Mortality Weekly Report, US Centers for Disease Control and Prevention (CDC) researchers analyzed COVID-19 surveillance and vaccination data from about 15,000 nursing home residents from Feb 14 to Mar 27, 2022, a period of widespread Omicron circulation.

Primary vaccination was considered receipt of two doses of an mRNA vaccine, a single dose of J&J, or an additional or booster dose at least 14 days before a positive COVID-19 test result. Participants who had received only one or no doses were considered unvaccinated.

A total of 15,090 nursing homes reported 89,671 infections each week from Feb 14 to Mar 27, 2022, and 15,102 facilities reported 89,969 weekly resident counts from Jan 31 to March 13, 2022. The analysis included 85,494 reports from 14,758 nursing homes.

The median weekly number of residents reported was 1,126,198, roughly 22% of whom had received primary vaccine doses only and 65% of whom received an additional or booster dose. Over 90% received mRNA COVID-19 vaccines.

An additional primary or booster dose of COVID-19 vaccine conferred greater estimated protection (relative adjusted VE, 46.9%; 95% confidence interval [CI], 44.8% to 48.9%) against COVID-19 infection, regardless of week or nursing home characteristics.

Overall, 7,510 infections were reported among 1,509,674 resident-weeks with primary series vaccination only and 11,334 infections were recorded among 4,416,401 resident-weeks after an additional or booster dose.

Weekly COVID-19 cases decreased in all vaccination groups during the study period, but rates among residents with an additional or booster dose were consistently lower than those among the unvaccinated and those who received the primary series vaccination only.

“All immunocompromised nursing home residents should receive an additional primary dose, and all nursing home residents should receive a booster dose, when eligible, to protect against COVID-19,” the researchers wrote.

“Efforts to keep nursing home residents up to date with vaccination should be implemented in conjunction with other COVID-19 prevention strategies, including testing and vaccination of nursing home staff members and visitors.”