AUTHOR=Kimingi Hannah W. , Kinyua Ann W. , Achieng Nicole A. , Wambui Kennedy M. , Mwangi Shaban , Nguti Roselyne , Kivisi Cheryl A. , Jensen Anja T. R. , Bejon Philip , Kapulu Melisa C. , Abdi Abdirahman I. , Kinyanjui Samson M. , CHMI-SIKA Study Team , Abdi Abdirahman I , Abebe Yonas , Audi Agnes , Bejon Philip , Billingsley Peter , Bull Peter C , Che Primus , Laurent Zaydah de , Hodgson Susanne H , Hoffman Stephen , James Eric , Jao Irene , Kamuya Dorcas , Kamuyu Gathoni , Kariuki Silvia , Kibinge Nelson , Kinyanjui Sam , Kivisi Cheryl , Koskei Nelly , Imwong Mallika , Lowe Brett , Makale Johnstone , Marsh Kevin , Marsh Vicki , Mohammed Khadija Said , Mosobo Moses , Murphy Sean C , Musyoki Jennifer , Muthui Michelle , Mwacharo Jedidah , Mwanga Daniel , Mwongeli Joyce , Ndungu Francis , Njue Maureen , Nyangweso George , Kimani Domitila , Ngoi Joyce M. , Musembi Janet , Ngoto Omar , Otieno Edward , Ogutu Bernhards , Olewe Fredrick , Oloo James , Omuoyo Donwilliams , Ongecha John , Ongas Martin O , Ooko Michael , Shangala Jimmy , Sim Betty Kim Lee , Tarning Joel , Wambua Juliana , Williams Thomas N , Winterberg Markus TITLE=Breadth of Antibodies to Plasmodium falciparum Variant Surface Antigens Is Associated With Immunity in a Controlled Human Malaria Infection Study JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.894770 DOI=10.3389/fimmu.2022.894770 ISSN=1664-3224 ABSTRACT=Background

Plasmodium falciparum variant surface antigens (VSAs) contribute to malaria pathogenesis by mediating cytoadhesion of infected red blood cells to the microvasculature endothelium. In this study, we investigated the association between anti-VSA antibodies and clinical outcome in a controlled human malaria infection (CHMI) study.

Method

We used flow cytometry and ELISA to measure levels of IgG antibodies to VSAs of five heterologous and one homologous P. falciparum parasite isolates, and to two PfEMP1 DBLβ domains in blood samples collected a day before the challenge and 14 days after infection. We also measured the ability of an individual’s plasma to inhibit the interaction between PfEMP1 and ICAM1 using competition ELISA. We then assessed the association between the antibody levels, function, and CHMI defined clinical outcome during a 21-day follow-up period post infection using Cox proportional hazards regression.

Results

Antibody levels to the individual isolate VSAs, or to two ICAM1-binding DBLβ domains of PfEMP1, were not associated with a significantly reduced risk of developing parasitemia or of meeting treatment criteria after the challenge after adjusting for exposure. However, anti-VSA antibody breadth (i.e., cumulative response to all the isolates) was a significant predictor of reduced risk of requiring treatment [HR 0.23 (0.10-0.50) p= 0.0002].

Conclusion

The breadth of IgG antibodies to VSAs, but not to individual isolate VSAs, is associated with protection in CHMI.