Increased levels of anti-PfCSP antibodies in post-pubertal females versus males immunized with PfSPZ Vaccine does not translate into increased protective efficacy.
Natasha Kc, L W Preston Church, Pouria Riyahi, Sumana Chakravarty, Robert A Seder, Judith E Epstein, Kirsten E Lyke, Benjamin Mordmüller, Peter G Kremsner, Mahamadou S Sissoko, Sara Healy, Patrick E Duffy, Said A Jongo, Vicente Urbano Nsue Ndong Nchama, Salim Abdulla, Maxmillian Mpina, Sodiomon B Sirima, Matthew B Laurens, Laura C Steinhardt, Martina Oneko, MingLin Li, Tooba Murshedkar, Peter F Billingsley, B Kim Lee Sim, Thomas L Richie, Stephen L Hoffman
Author Information
Natasha Kc: Sanaria Inc., Rockville, MD, United States.
L W Preston Church: Sanaria Inc., Rockville, MD, United States.
Pouria Riyahi: Sanaria Inc., Rockville, MD, United States.
Sumana Chakravarty: Sanaria Inc., Rockville, MD, United States.
Robert A Seder: Vaccine Research Center, National Institute of Heath, Bethesda, MD, United States.
Judith E Epstein: Naval Medical Research Center (NMRC), Silver Spring, MD, United States.
Kirsten E Lyke: Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, United States.
Benjamin Mordmüller: Institut für Tropenmedizin, Eberhard Karls Universität Tübingen and German Center for Infection Research, Tübingen, Germany.
Peter G Kremsner: Institut für Tropenmedizin, Eberhard Karls Universität Tübingen and German Center for Infection Research, Tübingen, Germany.
Mahamadou S Sissoko: Malaria Research and Training Center (MRTC), Mali National Institute of Allergy and Infectious Diseases International Centers for Excellence in Research, University of Science, Techniques and Technologies of Bamako, Bamako, Mali.
Sara Healy: Laboratory of Malaria Immunology and Parasitology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health (LMIV/NIAID/NIH), Rockville, MD, United States.
Patrick E Duffy: Laboratory of Malaria Immunology and Parasitology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health (LMIV/NIAID/NIH), Rockville, MD, United States.
Said A Jongo: Bagamoyo Research and Training Centre, Ifakara Health Institute, Bagamoyo, Tanzania.
Vicente Urbano Nsue Ndong Nchama: Ministry of Health and Social Welfare, Malabo, Equatorial Guinea.
Salim Abdulla: Bagamoyo Research and Training Centre, Ifakara Health Institute, Bagamoyo, Tanzania.
Maxmillian Mpina: Bagamoyo Research and Training Centre, Ifakara Health Institute, Bagamoyo, Tanzania.
Sodiomon B Sirima: Groupe de Recherche Action en Santé, Ouagadougou, Burkina Faso.
Matthew B Laurens: Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, United States.
Laura C Steinhardt: Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA, United States.
Martina Oneko: Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya.
MingLin Li: Sanaria Inc., Rockville, MD, United States.
Tooba Murshedkar: Sanaria Inc., Rockville, MD, United States.
Peter F Billingsley: Sanaria Inc., Rockville, MD, United States.
B Kim Lee Sim: Sanaria Inc., Rockville, MD, United States.
Thomas L Richie: Sanaria Inc., Rockville, MD, United States.
Stephen L Hoffman: Sanaria Inc., Rockville, MD, United States.
Background: While prior research has shown differences in the risk of malaria infection and sickness between males and females, little is known about sex differences in vaccine-induced immunity to malaria. Identifying such differences could elucidate important aspects of malaria biology and facilitate development of improved approaches to malaria vaccination. Methods: Using a standardized enzyme-linked immunosorbent assay, IgG antibodies to the major surface protein on (Pf) sporozoites (SPZ), the Pf circumsporozoite protein (PfCSP), were measured before and two weeks after administration of a PfSPZ-based malaria vaccine (PfSPZ Vaccine) to 5-month to 61-year-olds in 11 clinical trials in Germany, the US and five countries in Africa, to determine if there were differences in vaccine elicited antibody response between males and females and if these differences were associated with differential protection against naturally transmitted Pf malaria (Africa) or controlled human malaria infection (Germany, the US and Africa). Results: Females ≥ 11 years of age made significantly higher levels of antibodies to PfCSP than did males in most trials, while there was no indication of such differences in infants or children. Although adult females had higher levels of antibodies, there was no evidence of improved protection compared to males. In 2 of the 7 trials with sufficient data, protected males had significantly higher levels of antibodies than unprotected males, and in 3 other trials protected females had higher levels of antibodies than did unprotected females. Conclusion: Immunization with PfSPZ Vaccine induced higher levels of antibodies in post-pubertal females but showed equivalent protection in males and females. We conclude that the increased antibody levels in post-pubertal females did not contribute substantially to improved protection. We hypothesize that while antibodies to PfCSP (and PfSPZ) may potentially contribute directly to protection, they primarily correlate with other, potentially protective immune mechanisms, such as antibody dependent and antibody independent cellular responses in the liver.
