Abstract

We highlight here the results from our studies published in FY19: 1. Attaher O, Zaidi I, Kwan JL, Issiaka D, Samassekou MB, Cisse KB, Coulibaly B, Keita S, Sissoko S, Traore T, Diarra K, Diarra BS, Dembele A, Kanoute MB, Mahamar A, Barry A, Fried M, Dicko A, Duffy PE. Effect of Seasonal malaria chemoprevention on immune markers of exhaustion and regulation. 2019. Journal of Infectious Diseases. In Press Malian children that received seasonal malaria chemoprevention had fewer malaria episodes and showed significantly lower fold changes in CD4+PD1+ and CD4+PD1+LAG3+ compared to those children that did not receive SMC. Seasonal malaria chemoprevention had no observable effect on fold changes in CD8 T cells expressing PD1 or CD160. However, children receiving SMC showed greater increases in CD4+FOXP3+ T regulatory cells compared to SMC- children. Thus, the reduction of infections due to seasonal malaria chemoprevention may also prevent immune dysfunction. 2. Coelho CH, Gazzinelli-Guimaraes PH, Howard J, Barnafo E, Alani NAH, Muratova O, McCormack A, Kelnhofer E, Urban JF Jr, Narum DL, Anderson C, Langhorne J, Nutman TB, Duffy PE. Chronic helminth infection does not impair immune response to malaria transmission blocking vaccine Pfs230D1-EPA/Alhydrogel in mice. 2019. Vaccine. Feb 14;37(8):1038-1045. doi: 10.1016/j.vaccine.2019.01.027. Epub 2019 Jan 23. Helminths are complex metazoans that share the master capacity to downregulate the host immune response towards themselves and also to bystander antigens, including vaccines. Using an experimental murine model for a chronic helminth infection (Heligmosomoides polygyrus bakeri - Hpb), we evaluated whether prior infection alters the activity of Pfs230D1-EPA/Alhydrogel TBV in mice. Hpb-infected mice were immunized with Pfs230D1-EPA/Alhydrogel and the vaccine-specific immune response was compared with that in non-infected immunized mice. Pfs230D1 specific-IgG levels were similar between infected and uninfected mice as were absolute numbers of Pfs230D1-activated B cells and vaccine activity assessed by reduction of oocyst number in P. falciparum infected mosquitoes. Pfs230D1-EPA/Alhydrogel efficacy is not impaired by a chronic helminth infection in mice. The project comprised a series of 5 inter-related cohorts that compared groups receiving malaria drug interventions versus groups receiving no malaria intervention, and assessed the impact of these treatments on immunological and vaccine response endpoints. The studies were conducted at various sites around Bamako, Mali, where malaria transmission is intense during the rainy season (Jul-Dec) and is minimal during the dry season (Jan-Jun). In 3 of the 5 cohorts, the volunteers were drawn from among the participants in ongoing vaccine or drug trials. In FY19 , we completed the analysis of the project that studied the Effect of seasonal malaria chemoprophylaxis on immune exhaustion and regulatory markers and published the manuscript. Preliminary analysis of the year-long studies in adults and children has been completed and these will form the basis of future publications. We conducted a trial in Mali and recruited children from two villages; one where SMC had already been introduced and another where it had not. As expected, children receiving SMC had significantly lower plasmodium falciparum infections as well a clinical malaria cases compared to children in the placebo arm. We also demonstrated that the SMC+ group had significantly lower fold change in CD4+ PD1+ T cells than children in the SMC- group. Strikingly, the SMC+ group had a higher increase in T regulatory cells compared to the SMC- group.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI001147-09
Application #
10014199
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2019
Total Cost
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
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State
Country
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