Avaliação da resposta imune adaptativa induzida pela dose fracionada da vacina contra a febre amarela

Abstract

Yellow fever is a viral disease caused by an RNA arbovirus in the family Flaviviridae, endemic in the African continent, Central America and South America (“World Health Organization (WHO) - Yellow Fever Fact Sheet”, 2019). It is transmitted by the bite of the infected Aedes aegypti mosquito, and large cases of infection epidemics can occur when the virus is introduced into a populous region with a high density of the vector mosquito. The infection may be asymptomatic, or the symptoms may be nonspecific, including fever, chills, headaches and body aches, nausea and vomiting (“Centers for Disease Control and Prevention (CDC) - Yellow Fever”, 2019). More serious symptoms such as jaundice, bleeding and organ failure can occur and are associated with increased mortality. As a form of prevention, there is a vaccine composed of attenuated virus called 17D, homonymous with the strain of the virus used in its production, which has been used for approximately 8 decades (THEILER; SMITH, 1937a) . It is known that in the first days after the first dose of the vaccine, there is an increase in the number of activated B lymphocytes, consistent with an increase in circulating immunoglobulins and activated CD4+ and CD8+ T lymphocytes (MARTINS et al., 2007). In addition, there is an induction of memory CD8+ T lymphocytes capable of self-renewal, which can remain stable for up to 25 years (FUERTES MARRACO et al., 2015). There is also a mixed profile of pro and anti-inflammatory cytokines (SILVA et al., 2011) and the production of neutralizing antibodies that can last for many years after the two vaccine doses (CAMPI-AZEVEDO et al., 2019). However, this attenuated virus is expressed in chicken embryos (THEILER; SMITH, 1937a), and this limits its production capacity due to the need for pathogen-free embryos, whose availability is limited, and the low number of doses that can be generated by each embryo (from 100 to 300 doses). In addition, only 4 vaccine manufacturers are qualified by the World Health Organization (MONATH, 2005), generating the need to vaccinate people in risk areas with fractional doses, which consist of vaccines with one fifth of the regular dose (“World Health Organization - Fractional dose yellow fever vaccine as a dose-sparing option for outbreak response”, 2016). It has been shown that the fractionated dose was able to induce neutralizing antibodies against the yellow fever virus and induced a pro-inflammatory response very similar to that generated after administration of the regular dose of the vaccine (CAMPI-AZEVEDO et al., 2014). These results indicated that the fractional dose is effective and can be administered. With this project, we intend to evaluate the capacity of the fractionated dose of the yellow fever vaccine to generate effector T and B cells, antibody-producing plasma cells and memory subpopulations that participate in the immune response against the virus. We are particularly interested in the follicular helper T-cell (Tfh) and B-cell axis. This study will allow us to better understand the kinetics of vaccine-induced immunity against yellow fever and to assess whether the fractional dose, which has been widely used in risk regions, induces humoral and cellular immunological memory similar to the full dose.