Study shows it is possible to stimulate the immune system of babies against HIV

A study conducted at FM-USP (Faculty of Medicine, University of São Paulo) showed that it is possible to enhance the immune response of newborns against the HIV virus, which causes AIDS. The discovery, carried out in cell culture and described in the Journal of Infectious Diseases, expands the possibility of new therapeutic interventions to protect against infectious diseases in this period of life.

In the experiment, the researchers stimulated the innate response (first line of immune defense, which is not specific for a pathogen and involves cells such as macrophages, monocytes and neutrophils) in cells from the umbilical cord of babies whose mothers did not have HIV through a synthetic compound called CL097. Then, the team from the Medical Research Laboratory 56 incubated the virus in cells in vitro. The compound was shown to be efficient in promoting antiviral and inflammatory responses, inhibiting HIV replication in umbilical cord cells.

“The results reinforce the knowledge we already had that newborns have an immature immunity, therefore, they are more susceptible to viruses like HIV. However, we found that they are not as immunodeficient as previously thought, because their cells are capable of to respond very well to this type of stimulus with innate immunity agonists [substâncias que estimulam a primeira linha de defesa]. One of the study’s differentials was the use of this type of agonist [CL097], as it mimics the pathogen and makes it possible to reduce the viral infection”, says Maria Notomi Sato, a professor at FM-USP and the study’s main author.

The research was supported by FAPESP through a master’s scholarship granted to Anna Julia Pietrobon, Sato’s advisor.

According to the researchers, the strategy of improving the defense pathways can also be applied in the case of other viral infections, as well as to improve the effectiveness of vaccines in neonates.

“This finding undoubtedly contributes to the development of alternative antiviral treatments for babies. Tests were carried out with HIV, but it is very likely that this is the same with other viral or bacterial diseases. We still need more studies, but , in the future, we could offer these compounds to babies in order to activate the antiviral response, making them respond as well as adults, to the point of preventing the infection itself and fighting the infected cells”, explains Sato.

The immunity of babies

Because they still don’t have a fully formed immunity, newborns are more susceptible to infections by viruses, bacteria, fungi and other pathogens. This is because, in general, infant monocytes, macrophages, and dendritic cells secrete smaller amounts of cytokines—proteins that regulate the immune and inflammatory response.

There are also other factors that contribute to the immaturity of the adaptive immune response (specific for each pathogen) in newborns, such as the lack of a microenvironment for the interaction between T cells (lymphocytes responsible for cell immunity) and the B cells (antibody-producing lymphocytes).

“It takes some time for babies’ immunity to fully mature. That’s because, although most of the antibodies come from the mother, the cellular part of the immune response is slower. Therefore, there is this greater susceptibility to various types of infection in the postpartum period. Knowing that, we were looking for adjuvants that could stimulate this immature immune response,” explains Pietrobon.

The researcher points out that, in babies, the most common form of HIV transmission is vertical — when the infected mother infects the child during pregnancy, labor or breastfeeding. “It is estimated that this type of transmission is responsible for 9% of AIDS cases in the world”, he informs.

But it is noteworthy that, currently, treatments with AZT or antiretroviral cocktails during pregnancy and childbirth have reduced the risk of vertical transmission. “In Brazil, fortunately, almost 100% of women who need it have access. However, not all countries offer this type of care for HIV-positive pregnant women and it is important to seek therapeutic alternatives”, says Sato.

Activated macrophage

The study conducted at FM-USP focused on macrophages, which are target cells for HIV and, when infected, become a reservoir for the virus. “This ends up sustaining the viral load of these patients. Another problem is that macrophages are a little more resistant to the action of antiretroviral drugs. For these factors, they have a very large participation and contribution in the pathogenesis of the disease and in the difficulty of finding a cure for it. HIV,” explains Pietrobon.

In the experiment with newborn cells, the team demonstrated that it is possible to activate viral combat pathways in macrophages with adjuvants that enhance the innate immune response to the point of preventing infection and viral replication.

“As newborns still do not have memory T cells, it is thought that, when they come into contact with a virus —whether still inside the mother’s womb, during delivery or after birth—, macrophages are the main targets of infection. . Therefore, it is very positive to have this alternative to enhance the defense of babies,” he says.