Immune response to CoronaVac is less intense in men over 55 years – 25/08/2021

The response to the covid-19 virus in people who took the two doses of the CoronaVac vaccine is much less intense in most men over 55 years of age, according to preliminary results of a research coordinated by the Faculty of Medicine of USP.

From the analysis of blood samples, the study indicated that only a third of men over 55 years old have a strong antibody response, or cells against the virus, and this already diminished response is accentuated after the age of 80 years.

In the article that exposes the results, the authors of the research recommend that a third dose of vaccine be applied, first in people over 80 years of age, and, when possible, in people over 60 years of age. The conclusions of the work are in pre-print (previous version of a scientific article) published on the website MedRXiv on August 23rd.

“The study was based on the collection of blood from 70 people who were convalescent, that is, who had already had the disease and 100 people who were vaccinated with two doses of CoronaVac, with a minimum interval of four weeks to be collected “, explains Professor Jorge Kalil, from FMUSP, one of the authors of the work.

Three parameters were verified: “The antibody response against sars-cov-2, more specifically to three types of coronavirus proteins, responsible for its structure and adhesion to cells; neutralizing antibodies, that is, those that actually inactivate the virus; and the cellular response, which occurs through a proliferation of defense cells, the lymphocytes, in a culture of blood cells, after stimulation with virus fragments, the so-called viral protein peptides”.

During the study, the people analyzed were separated by age and gender.

“When samples were stratified by age and correlated with immunological measurements, it was possible to establish a threshold at 55 years among men, when the response to the virus, whether from antibodies or cells, is much weaker compared to to the other groups tested”, reports professor Edécio Cunha Neto, from FMUSP, one of the authors of the work.

“For example, the production of two essential proteins for the functioning of T cells, which make the body’s defense, was measured, interleukin-2 and interferon-gamma. In men over 55 years, there was no difference in interferon- gamma, but interleukin-2, which points to a possible difficulty in the production of memory T cells, which guarantee the immune response against the virus long after vaccination.”

Coronavirus Vaccine - Getty Images/iStock - Getty Images/iStock

Coronavirus vaccine

Image: Getty Images/iStock

Decreased response

According to Professor Jorge Kalil, only a third of men over 55 years have clearly strong antibody and cell responses against the coronavirus, some of them have only one of them and the others have none.

“The diminished response to the vaccine increases after 80 years of age. This demonstrates well that the vaccine regimen that was used is not sufficient to provide reasonable coverage against serious disease and against death”, he points out.

“This was already verified in practice when the effectiveness of the vaccine was seen in the field and it was seen that older people continue to have more of the disease, despite being immunized with CoronaVac.”

According to the professor at FMUSP, in terms of public policies, the results of the study reinforce the recommendations of the Technical Advisory Committee on Immunizations (Cetai), which advises the PNI (National Immunization Program) of the Ministry of Health.

“The Commission advised the Ministry to apply the third dose of vaccines for those who took two doses of CoronaVac and are over 80 years old, and vaccinate people over 60 years old with the third dose when possible”, he points out. “Very likely, a heterologous vaccine will be applied, that is, a vaccine other than Coronavac, preferably either AstraZeneca or Pfizer.”

“There is currently an ongoing study in Brazil, sponsored by the Ministry of Health, which is seeing how effective it is to immunize people who have received two doses of Coronavac with a second dose”, reports Kalil.

“The second dose can be from Coronavac, AstraZeneca, Pfizer or Janssen, and what will be evaluated is the amount of neutralizing antibodies that will be obtained after this third dose. This study is ongoing and is expected to that in a month we will already have these results, which is very important for the definition of which vaccine will be used in the third dose.”

“Vaccines with inactivated viruses, such as Coronavac, have few side effects, however, their immunogenicity is lower”, explains Professor Cunha Neto.

“It is known that this type of vaccine does little to stimulate the immune system, especially that of the elderly. This same phenomenon was not observed in the studies carried out with the vaccine by AstraZeneca, Pfizer and Moderna, which showed that these vaccines induce a strong response. , even in the elderly”, concludes Professor Kalil.

The research was coordinated by FMUSP and part of the analyzes took place at the InCor (Instituto do Coração) of the Hospital das Clínicas (HC) at FMUSP. The studies also had the collaboration of the ICB (Institute of Biomedical Sciences) of USP and the Federal University of São Paulo (Unifesp).

In perspective

For the infectologist and researcher at Fiocruz André Siqueira, this was a very well-conducted study, by a strong group of researchers, which shows in a robust way, with different techniques, that the immune response of elderly individuals to the vaccine is less than that of younger individuals, and also smaller, comparatively, than that of those who had the disease.

“These results are as expected, but shown in a methodologically appropriate way”, says the doctor, who did not participate in the study, but agreed to comment on it for the Jornal da USP.

In relation to drawing more general conclusions from the results, he points out some limitations. “First, the correlate of protection is not well defined, that is, what levels of antibodies and what levels of cellular immune response are needed to promote protection against different outcomes, from infection to hospitalization and death. So, I don’t see how this can be generalized as the authors suggest”, says Siqueira.

He considers that the study data alone are not enough to indicate the need for a third dose. For this, he says clinical studies are needed, such as the one mentioned by Jorge Kalil, which is in progress.

“Only in this way can we assess what the gain is with a third dose of the same vaccine or another. Without that, we are left with the assumption, which seems obvious, that the more doses, the more protection – but this is not all that mathematical “says Siqueira.

The infectologist also makes a reservation that one can only speak of a new dose considering the amount of doses available for the population as a whole and the level of transmission.

“The higher the level of transmission, the greater the risk of infection. I think we need to analyze other data to say that it is better to revaccinate these older individuals than to prioritize full population coverage, which will lead to a reduction in transmission .”

Vaccine and risk

About the arrival of the Delta variant, André Siqueira says that vaccines, in general, have shown a relatively lower effectiveness, with only one dose, and with two doses they still present a good response.

“But without a doubt, this makes it clearer that we cannot rely solely on vaccines as a method of controlling the pandemic. If we let the virus run freely in the community, this will lead to a high number of cases, especially among the elderly. Some of these individuals, even if we apply several vaccines, different or not, they will continue without having the adequate response. So reducing transmission with other measures is essential.”

In fact, the relaxation of restrictions and the discussion about booster doses are taking place in several countries, and may give the population the perception that vaccines are now the only action front to contain the pandemic.

But this is not true, according to Lorena Barberia, a professor at the Faculty of Philosophy, Letters and Human Sciences (FFLCH) at USP.

“The experience of several countries, such as Israel, which advanced in vaccination much faster and with greater vaccination coverage, has reinforced that vaccines work as part of a package of measures to control the pandemic and not as a a substitute,” says she, who is one of the network coordinators who research responses to the pandemic and its social consequences.

“In other words, vaccines continue to be the best way for individuals to protect themselves, but societies cannot treat them as their only defense,” he emphasizes. It also endorses that people need to have a more complete view of risk.

“We have tried to alert using comparisons that the public can understand better. For example: the vaccine is a bulletproof vest. You can use the vest, but when you leave home in the context that we live throughout 2021, with number of cases high, low testing and flexibility of physical distance measures, there is a high risk of becoming infected while on the street.”