Third dose of COVID-19 vaccines increases protection against omicron, study shows

Researchers followed 286 volunteers during a wave of COVID-19 in the Northeast region of Brazil in the first quarter of 2022. The number of cases fell among those who had been vaccinated with three doses, and they had more neutralizing antibodies than subjects who had not completed the vaccination scheme even when previously infected.

André Julião | Agência FAPESP – A study involving 286 volunteers conducted during a surge of COVID-19 cases in Bahia, a state in Northeast Brazil, reinforces the importance of the third dose of vaccine to protection against all main variants of SARS-CoV-2, including omicron.

An article on the study is published in the Journal of Medical Virology. The findings also showed that people who had been given three doses of the vaccine had more antibodies capable of neutralizing the virus than those who had not completed the vaccination scheme and even people who had previously had COVID-19. More than 80% of the participants who tested positive for the disease had not received the booster dose, which is normally administered after the two-dose standard scheme.

“Although some of the participants who had had the disease previously had more antibodies that recognized the virus, those who had received three doses of the vaccine had antibodies of higher quality, meaning they not only recognized but effectively neutralized the virus,” Jaime Henrique Amorim, last author of the article, told Agência FAPESP. Amorim is a professor at the Federal University of West Bahia (UFOB) and led the study with penultimate author Luiz Mário Ramos Janini, a professor at the Federal University of São Paulo's Medical School (EPM-UNIFESP) supported by a Thematic Grant from FAPESP. 

The study population consisted of patients with flu-like symptoms seeking treatment at a clinic in Barreiras, Bahia State, during an outbreak of omicron that occurred between January and March 2022. Nasopharyngeal swabs and blood samples were collected from over 230 volunteers.

The viruses present in the swabs and samples were isolated and sequenced, confirming that they were omicron. Blood serum samples were then separated to test the action of antibodies on this variant and on the original Wuhan strain that gave rise to the pandemic.

“The antibodies found in samples from patients who had been given three doses of vaccine neutralized both the Wuhan strain and the omicron variant. Antibodies from unvaccinated patients and patients given one or two doses did not,” said Robert Andreata-Santos, one of the first three authors of the article, alongside Jéssica Pires Farias and Josilene Pinheiro, researchers at UFOB. Andreata-Santos is a postdoctoral research fellow at EPM-UNIFESP with a scholarship from FAPESP.

Protection

Only 16 of the vaccinated subjects who tested positive had taken a third dose. Among the 189 who tested negative, 166 were vaccinated and 51 had taken three doses.

The study was conducted at a time when few people had taken a third dose of any of the COVID-19 vaccines then available. Most had taken two doses of CoronaVac (Butantan Institute/Sinovac) or Oxford/AstraZeneca. Pfizer’s was then the most widely available vaccine for the booster dose.

“As expected, we found that vaccination does not necessarily prevent infection. What's new in our study is that people vaccinated with three doses had antibodies that neutralized even omicron, which appeared when the vaccines in use already existed,” said Luis Carlos de Souza Ferreira, another co-author of the article. He is a professor at the University of São Paulo's Institute of Biomedical Sciences (ICB-USP) and heads the Pasteur-USP Science Platform. At the time of the study, he had a research grant from FAPESP. 

According to Ferreira, the results are globally relevant because they prove that booster doses of existing vaccines should be given to everyone, and also that the different combinations of vaccines administered in Brazil are efficacious in terms of protecting people against severe disease when infected even by recent variants such as omicron.

“Most research on the third dose was done in countries of the northern hemisphere, which were more homogeneous in terms of the vaccine brands used. What we have now is relevant to Brazilian reality,” Amorim said.

Preliminary results of a new analysis conducted recently by the group in the same city show that administration of a fourth dose also had a significant effect. The researchers observed an even smaller number of cases of the disease even among people who were infected by the virus.

“The fourth dose appears to be as important as the third,” Andreata-Santos said. “Until vaccines produced specifically for novel variants are available, it’s vital to keep levels of neutralizing antibodies high in the population, and that can only be done with booster doses.”

The study was supported by FAPESP via a postdoctoral scholarship awarded to Maria Fernanda de Castro Amarante.

It was also supported by Serrapilheira Institute, a private-sector research funder, and federal funders CAPES (the Ministry of Education’s higher research council), CNPq (the National Scientific and Technological Research Council), and FINEP (the Brazilian Innovation Agency, an arm of the Ministry for Science, Technology and Innovation).

The article “The third vaccine dose significantly reduces susceptibility to the B.1.1.529 (Omicron) SARS-CoV-2 variant” is at: https://onlinelibrary.wiley.com/doi/10.1002/jmv.28481.