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Abstracts of Oral Presentations
OA-722 Assessment of naturally acquired humoral immunity against malaria protecting against controlled human malaria infection (CHMI)
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  1. Nouhoun Barry1,4,6,
  2. Stephanie Sefried1,4,
  3. Nicole Peter1,4,
  4. Freia-Raffaella Lorenz2,
  5. Raffiou Adamou3,
  6. Thomas L Richie5,
  7. Stephen L Hoffman5,
  8. Peter Kremsner1,3,4,
  9. Jeannot Zinsou3,
  10. Ayola Akim Adegnika1,3,4,
  11. Benjamin Mordmüller2,
  12. Matthew McCall2,
  13. Rolf Fendel1,3,4
  1. 1Universitätsklinikum Tübingen, Deutschland
  2. 2Radboud University Medical Center (RadboudUMC), The Netherland
  3. 3Centre de Recherche Medical de Lambaréné (CERMEL), Gabon
  4. 4Naval Medical Research Center (NMRC), Unites States
  5. 5Sanaria inc, USA

Abstract

Background A successful malaria vaccine should, depending on the targeted stage of the malaria life cycle, induce both humoral and cellular immune responses. Naturally acquired immunity (NAI) against malaria is thought to target mostly the blood stage and protects individuals against symptomatic and severe disease, but often fails to protect against infection per sé. A better understanding of the mechanisms of NAI and its role in all stages of the life cycle might lead to improved vaccine design of the next-generation malaria vaccine.

Methods In Lambaréné, Gabon, a study was conducted in which semi-immune individuals underwent repeated controlled human malaria infections (CHMI) using direct venous inoculation of fully viable cryopreserved Plasmodium falciparum (Pf) sporozoites (PfSPZ, strains NF54 and 7G8). Participants were randomized into two arms allocated 1:1. In arm A, participants were infected using Pf strain 7G8 followed by five infections with Pf strain NF54. In arm B, participants were infected four times with Pf strain NF54 followed by one infection with Pf strain 7G8 and finally one infection with NF54. Here, we investigate the immune response against Pf antigens potentially relevant for the protective immune response against malaria. Selected antigens were expressed using mammalian or bacterial expression systems and subsequently purified. Humoral immune response was assessed by indirect ELISA.

Results In total 56 participants were enrolled. Their average age was 28 +/- 6 years. Most participants were male (82%). At baseline, Pf-specific antibodies ranged from 5 to 100 µg/ml in plasma, with a predominance of antibodies against blood stage antigens, such as AMA1 and merozoite surface proteins. The antibody responses against these antigens showed minor fluctuations during follow-up.

Conclusion The investigation is ongoing, and further antigens will be investigated. Specifically, the dynamics of antibody responses throughout the study period, also regarding antibody isotype and function, will be presented.

https://doi.org/10.1136/bmjgh-2023-EDC.50

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