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PA-049
SOLUBLE HLA-G LEVEL EFFECT ON GMZ2 SPECIFIC IgG PRODUCTION AFTER IMMUNISATION
  1. Odilon Nouatin1,
  2. Ulysse Ateba Ngoa1,
  3. Jean Claude Dejon1,
  4. Jean R Edoa1,
  5. Andreas Homoet2,
  6. Julie Englhon Engelhon2,
  7. Marguerite Massinga-Louembe1,
  8. Meral Esen2,
  9. Michael Theisen3,
  10. Kim Lee Sim4,
  11. Thomas Richie4,
  12. Adrian Jf Luty5,
  13. Kabirou Moutairou6,
  14. Stephen Hoffman7,
  15. Peter Kremsner2,
  16. Bertrand Lell1,
  17. Benjamin Mordmüller2,
  18. Ayola Adegnika1
  1. 1CERMEL, Gabon
  2. 2ITM Tübingen, Germany
  3. 3Statens Serum Institut, Denmark
  4. 4Sanaria Inc., United States of America
  5. 5IRD, Benin
  6. 6National University of Benin, Benin
  7. 7Sanaria Inc., United States of America

Abstract

Background Malaria is a major public health problem particularly in Africa. Despite the relatively good immunogenicity profile of the vaccine candidates in naive population, most of them are poorly immunogenic in malaria endemic population. This could be due to an induction of various immune regulatory mechanisms. It has recently been shown that high levels of an immune regulatory molecule sHLA-G in infants increased the risk of malaria, and question may arise as to whether it can equally impair vaccine induced immune response. In this study we have assessed the correlation between sHLA-G and the immune response induced by GMZ2 a blood stage malaria vaccine candidate.

Methods It was an observational study nested within a phase Ib trial aiming to assess the safety, immunogenicity and efficacy of GMZ2 adjuvanted with CAF01, on fifty Gabonese adults lifelong exposed to Plasmodium spp. Three doses of either the vaccine candidate or Rabies vaccine were injected at Day 0, Day 28, Day 56. Peripheral blood sample was collected at Day 0 and Day 7 after the first vaccine administration as well as 28 days after the third vaccine administration (Day 84). sHLA-G level was measured by ELISA on Day 0 and Day 7, and the anti GMZ2, anti MSP3, Glurp IgG concentrations were determined by ELISA on Day 0, 7 and 84. Vaccine efficacy was assessed using PfSPZ Challenge.

Results sHLA-G level was significantly increased from Day 0 to Day 7 (p=0.004) and correlated with a significant decrease of anti-GMZ2 total IgG (r=–0.35, p=0.04). No correlation was found between sHLAG and anti MSP3, Glurp IgG production. Interestingly, individuals who did not develop malaria after the challenge had a lower level of sHLA-G at baseline (p=0.03).

Conclusions Vaccination with GMZ2 induces an increase of sHLA-G level resulting in a decrease of vaccine immunogenicity. This could have an implication for the design of malaria vaccine candidates in semi-immune individuals.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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