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Longitudinal analysis of gamma delta T cell subsets during malaria infections in Malian adults.

ABSTRACT: BACKGROUND:Immunity that limits malarial disease is acquired over time, but adults living in endemic areas continue to become infected and can require treatment for clinical illness. Gamma delta (??) T cells, particularly the V?2+?subset, have been associated with development of clinical malaria in children. In this study, the dynamics of total ?? T cells, V?2+?and V?2- T cells were measured during a malaria transmission season in Malian adults. METHODS:This study explored ?? T cell dynamics and Plasmodium falciparum infection outcomes over the course of the malaria transmission season in Malian adults enrolled in the placebo arm of a double-blind randomized vaccine trial. All volunteers were treated with anti-malarial drugs prior to the start of the transmission season and blood smears were assessed for P. falciparum infection every 2 weeks from July 2014 to January 2015. The study participants were stratified as either asymptomatic infections or clinical malaria cases. V?2+?and V?2- ?? T cell frequencies and activation (as measured by CD38 expression) were measured in all study participants at baseline and then every 2 months using a whole blood flow cytometry assay. RESULTS:Forty of the forty-three subjects became infected with P. falciparum and, of those, 21 individuals were diagnosed with clinical malaria at least once during the season. The ?? T cell percentage and activation increased over the duration of the transmission season. Both the V?2+?and V?2- ?? T cells were activated by P. falciparum infection. CONCLUSION:?? T cells increased during a malaria transmission season and this expansion was noted in both the V?2+?and V?2- ?? T cells. However, neither expansion or activation of either ?? T cell subsets discriminated study participants that had asymptomatic infections from those that had clinical malaria cases.

SUBMITTER: Diallo H

PROVIDER: S-EPMC6416881 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Longitudinal analysis of gamma delta T cell subsets during malaria infections in Malian adults.

Diallo Hama H Katile Abdoulaye A Kwan Jennifer L JL Sissoko Mahamadou S MS Healy Sara A SA Doumbo Ogobara K OK Duffy Patrick E PE Zaidi Irfan I

Malaria journal 20190312 1

<h4>Background</h4>Immunity that limits malarial disease is acquired over time, but adults living in endemic areas continue to become infected and can require treatment for clinical illness. Gamma delta (γδ) T cells, particularly the Vδ2+ subset, have been associated with development of clinical malaria in children. In this study, the dynamics of total γδ T cells, Vδ2+ and Vδ2- T cells were measured during a malaria transmission season in Malian adults.<h4>Methods</h4>This study explored γδ T ce ...[more]

PMID: 30866943

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Project description:ObjectivesThe objectives were to evaluate the safety, reactogenicity, and allele-specific immunogenicity of the blood-stage malaria vaccine FMP1/AS02A in adults exposed to seasonal malaria and the impact of natural infection on vaccine-induced antibody levels.DesignWe conducted a randomized, double-blind, controlled phase I clinical trial.SettingBandiagara, Mali, West Africa, is a rural town with intense seasonal transmission of Plasmodium falciparum malaria.ParticipantsForty healthy, malaria-experienced Malian adults aged 18-55 y were enrolled.InterventionsThe FMP1/AS02A malaria vaccine is a 42-kDa recombinant protein based on the carboxy-terminal end of merozoite surface protein-1 (MSP-1(42)) from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The control vaccine was a killed rabies virus vaccine (Imovax). Participants were randomized to receive either FMP1/AS02A or rabies vaccine at 0, 1, and 2 mo and were followed for 1 y.Outcome measuresSolicited and unsolicited adverse events and allele-specific antibody responses to recombinant MSP-1(42) and its subunits derived from P. falciparum strains homologous and heterologous to the 3D7 vaccine strain were measured.ResultsTransient local pain and swelling were more common in the malaria vaccine group than in the control group (11/20 versus 3/20 and 10/20 versus 6/20, respectively). MSP-1(42) antibody levels rose during the malaria transmission season in the control group, but were significantly higher in malaria vaccine recipients after the second immunization and remained higher after the third immunization relative both to baseline and to the control group. Immunization with the malaria vaccine was followed by significant increases in antibodies recognizing three diverse MSP-1(42) alleles and their subunits.ConclusionsFMP1/AS02A was well tolerated and highly immunogenic in adults exposed to intense seasonal malaria transmission and elicited immune responses to genetically diverse parasite clones. Anti-MSP-1(42) antibody levels followed a seasonal pattern that was significantly augmented and prolonged by the malaria vaccine.

Dataset Information

Longitudinal analysis of gamma delta T cell subsets during malaria infections in Malian adults.

Publications

Longitudinal analysis of gamma delta T cell subsets during malaria infections in Malian adults.

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