Increased levels of anti-PfCSP antibodies in post-pubertal females versus males immunized with PfSPZ Vaccine does not translate into increased protective efficacy.


Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2022
Historique:
received: 29 07 2022
accepted: 30 09 2022
entrez: 17 11 2022
pubmed: 18 11 2022
medline: 22 11 2022
Statut: epublish

Résumé

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. Using a standardized enzyme-linked immunosorbent assay, IgG antibodies to the major surface protein on 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. 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.

Sections du résumé

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
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.

Identifiants

pubmed: 36389797
doi: 10.3389/fimmu.2022.1006716
pmc: PMC9641621
doi:

Substances chimiques

Malaria Vaccines 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1006716

Informations de copyright

Copyright © 2022 KC, Church, Riyahi, Chakravarty, Seder, Epstein, Lyke, Mordmüller, Kremsner, Sissoko, Healy, Duffy, Jongo, Nchama, Abdulla, Mpina, Sirima, Laurens, Steinhardt, Oneko, Li, Murshedkar, Billingsley, Sim, Richie and Hoffman.

Déclaration de conflit d'intérêts

NK, LC, PR, SC, TM, PB, BS, TR and SH are salaried employees of Sanaria Inc., the developer and owner of PfSPZ Vaccine and sponsor of the clinical trials. In addition, BS and SH have a financial interest in Sanaria Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare this study received funding from Sanaria Inc. The funder had the following involvement in the study: proposal of the study hypothesis, conduct of the ELISAs and data analysis.

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Auteurs

Natasha Kc (N)

Sanaria Inc., Rockville, MD, United States.

L W Preston Church (LWP)

Sanaria Inc., Rockville, MD, United States.

Pouria Riyahi (P)

Sanaria Inc., Rockville, MD, United States.

Sumana Chakravarty (S)

Sanaria Inc., Rockville, MD, United States.

Robert A Seder (RA)

Vaccine Research Center, National Institute of Heath, Bethesda, MD, United States.

Judith E Epstein (JE)

Naval Medical Research Center (NMRC), Silver Spring, MD, United States.

Kirsten E Lyke (KE)

Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, United States.

Benjamin Mordmüller (B)

Institut für Tropenmedizin, Eberhard Karls Universität Tübingen and German Center for Infection Research, Tübingen, Germany.
Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, Netherlands.

Peter G Kremsner (PG)

Institut für Tropenmedizin, Eberhard Karls Universität Tübingen and German Center for Infection Research, Tübingen, Germany.
Centre de Recherches Medicales de Lambaréné, Lambaréné, Gabon.

Mahamadou S Sissoko (MS)

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 (S)

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 (PE)

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 (SA)

Bagamoyo Research and Training Centre, Ifakara Health Institute, Bagamoyo, Tanzania.

Vicente Urbano Nsue Ndong Nchama (VUNN)

Ministry of Health and Social Welfare, Malabo, Equatorial Guinea.

Salim Abdulla (S)

Bagamoyo Research and Training Centre, Ifakara Health Institute, Bagamoyo, Tanzania.

Maxmillian Mpina (M)

Bagamoyo Research and Training Centre, Ifakara Health Institute, Bagamoyo, Tanzania.
Swiss Tropical Public Health Institute, Basel, Switzerland.
University of Basel, Basel, Switzerland.

Sodiomon B Sirima (SB)

Groupe de Recherche Action en Santé, Ouagadougou, Burkina Faso.
Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina Faso.

Matthew B Laurens (MB)

Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, United States.

Laura C Steinhardt (LC)

Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA, United States.

Martina Oneko (M)

Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, Kenya.

MingLin Li (M)

Sanaria Inc., Rockville, MD, United States.

Tooba Murshedkar (T)

Sanaria Inc., Rockville, MD, United States.

Peter F Billingsley (PF)

Sanaria Inc., Rockville, MD, United States.

B Kim Lee Sim (BKL)

Sanaria Inc., Rockville, MD, United States.

Thomas L Richie (TL)

Sanaria Inc., Rockville, MD, United States.

Stephen L Hoffman (SL)

Sanaria Inc., Rockville, MD, United States.

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