Lymphocyte subset analyses in healthy adults vaccinated with yellow fever 17DD virus

Abstract

In this study the kinetics of humoral and cellular immune responses in first-time vaccinees and re-vaccinees with the yellow fever 17DD vaccine virus was analyzed. Flow cytometric analyses were used to determine percentual values of T and B cells in parallel to the yellow fever neutralizing antibody production. All lymphocyte subsets analyzed were augmented around the 30th post vaccination day, both for first-time vaccinees and re-vaccinees. CD3 + T cells increased from 30.8% (SE ± 4%) to 61.15% (SE ± 4.2%), CD4 + T cells from 22.4% (SE ± 3.6%) to 39.17% (SE ± 2%) with 43% of these cells corresponding to CD4 + CD45RO + T cells, CD8 + T cells from 15.2% (SE ± 2.9%) to 27% (SE ± 3%) with 70% corresponding to CD8 + CD45RO + T cells in first-time vaccinees. In revaccinees, the CD3 + T cells increased from 50.7% (SE ± 3%) to 80% (SE ± 2.3%), CD4 + T cells from 24.9% (SE ± 1.4%) to 40% (SE ± 3%) presenting a percentage of 95% CD4 + CD45RO + T cells, CD8 + T cells from 19.7% (SE ± 1.8%) to 25% (SE ± 2%Key words: yellow fever -vaccine -flow cytometry -neutralizing antibodies -lymphocyte subsets Yellow fever (YF) is a viral illness transmitted by infected mosquitoes (Aedes and Haemagogus genus) with yellow fever virus (YFV), which belongs to the Flavivirus genus, Flaviviridae family (Monath & Heinz 1996). It remains a serious health problem in endemic areas of tropical and subtropical Africa and South America (Vasconcelos 2003). Since the 19th century, studies about YF immunization have been accomplished (WHO 2001a). The YF 17D vaccine virus strain is one of the most effective and safe vaccines available. Immunization with the 17D vaccine strain induces a long-term neutralizing antibody response and provides excellent protection against infection with the virulent YFV (Wisseman & Sweet 1962). In 1937, the production of the YF 17DD vaccine virus substrain was started in Brazil, and has been in continuous use for 60 years (Post et al. 2001). The YFV 17DD vaccine is highly immunogenic and induces neutralizing antibody persistent at least 10 years and in some individuals up to 30 years or more (WHO 2001b).Although the YF 17D virus strain and the 17DD substrain are the most successful vaccines developed to date, recently, rare cases of postvaccinal neurological disorders have been recorded (Chan et al. 2001, Martin et al. 2001, Vasconcelos et al. 2001 .Despite the large literature on the humoral immune response to the YF vaccine virus, few works of the evaluation of cellular immune response, in particular T cell responses have been published (Reinhardt et al. 1998, Co et al. 2002, van der Most et al. 2002. The capacity of vaccines to activate the cellular immune system and induce T cell memory is an important mechanism of protection against wild-type viral infection. T cells often recognize more conserved epitopes that do not change due to antibody mediated selection pressure (Whitton & Oldstone 1996, Reinahrdt et al. 1998. Co and collaborators (2002) studying the T cell responses to YFV 17D in four volunteers could observ...

Dynamics of the Cytotoxic T Cell Response to a Model of Acute Viral Infection

“…ϩ -, and CD8 ϩ -based antiviral immune response (6,9,10,12,16,(30)(31)(32)(33)(34). Although some of these studies used either peptide pools or tetramer-based approaches to address the response to a limited number of viral epitopes (6,9,33), or calculated the percentage of different immune cellular compartments that represented clones induced by vaccination with YFV (reviewed in reference 16), the clonal breadth and complexity of the response to a viral infection has been beyond the reach of available methods.…”

“…Although helper T cells are clearly required for the production of YFV-specific Abs (including nAbs), different studies have reported variable levels of induction of CD4 ϩ T cells upon vaccination with YFV (30,31). Some analyses have revealed that cytokineproducing YFV-specific CD4 ϩ T cells can be detected as early as day 2 postvaccination and that they return to baseline by day 28, suggesting that the kinetics of CD4 ϩ T cells precede those of CD8 ϩ T cells (12,32).…”

Immune activation alters cellular and humoral responses to yellow fever 17D vaccine

“…Studies have suggested that the ability of YF-17D to infect dendritic cells and activate multiple Toll-like receptors may be essential for generating this potent immune response (8,(12)(13)(14). The YF-17D vaccine provides a model to study the immune response to vaccination in human populations, including both cellular and humoral responses, and to dissect the mechanisms of effective vaccine responses (10,(15)(16)(17)(18). Defining vaccine efficacy in African populations is of paramount importance, as these populations are targeted by most of the currently tested vaccines for HIV, tuberculosis, malaria, and dengue virus (DENV) (19).…”

Yellow Fever Vaccination Elicits Broad Functional CD4 + T Cell Responses That Recognize Structural and Nonstructural Proteins

“…Therefore, the YFV 17D vaccine is an excellent and important model for studying human antiviral immunity. Multiple studies have investigated the attributes and dynamics of CD4 ϩ and CD8 ϩ T cell responses following YF vaccination (8)(9)(10)(11)(12). By using a variety of readouts, these studies demonstrated that YFVspecific CD8 ϩ T cell responses are polyfunctional, exhibit distinct surface phenotypic markers, and peak approximately 2 to 4 weeks after vaccination.…”