Sex-based differences in HIV-T cell interaction

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Sex-based differences in T cell response

Publication . Gonçalves, Juliana; Soares, Helena

To understand the immune system and to unveil mechanism of diseases there is a need for studies in fundamental research. However, the majority of research has been conducted ignoring one of the most important variables, sex. Accumulating evidence reinforces the role of sex differences in immune response and consequently in diseases outcomes. Specifically, women mount a stronger immune response contributing both to faster clearance of pathogens and to increased vaccine efficacy. However, this stronger immune response also accounts for higher female susceptibility to autoimmune and to chronic diseases. The urgent need to understand the molecular mechanisms and players underpinning dimorphic immune responses was further highlighted by COVID-19 pandemic. On one hand, male sex was considered a risk factor for death and hospitalization; on the other hand, females are at higher risk to develop long COVID. Despite these clear sex-based differences in immune responses to SARS-CoV-2 infection, women in particular life stages, pregnancy and lactation, were excluded from COVID-19 vaccine trials. While pregnancy is considered a risk factor for COVID-19 severity, immune protection transfer in utero and through breastmilk is considered essential to provide protection to infants. Specially relevant since recent studies, particularly from Brazil, have shown that infants are the children’s group with worse COVID-19 outcomes. For this past year we addressed the effects of COVID-19 infection and vaccination in the particular women’s physiological stages of pregnancy and lactation, respectively. We demonstrated that in SARS-CoV-2 infected pregnant women IgG transfer ratio is inefficient. In contrast, we observed that BNT162b2 vaccination of lactating women leads to spike-reactive IgA and IgG transfer to the breastmilk. Functionally, we found that these antibodies were non-neutralizing. Importantly, we also observed for the first time that spike-reactive T cells were transferred to the suckling infant through breastmilk. Further studies are required to determine whether the transferred antibodies and spike-T cells can mediate protection in the suckling infant. By identifying a new immunomodulatory hormone, this thesis highlighted the need of exploring the molecular underpinnings of immune sex bias. Moreover, it will be crucial to fill the data gap between men and women not only concerning pathologies but also the immune response to vaccines and/or infections and how it may be affected by the women’s developmental stage, as highlighted by our results in COVID-19 vaccinated lactating women and COVID-19 infected pregnant women, respectively.

2021-10-29Tese de doutoramento

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Fundação para a Ciência e a Tecnologia

Número da atribuição

PD/BD/128343/2017