Increased levels of anti-PfCSP antibodies in post-pubertal females versus males immunized with PfSPZ Vaccine does not translate into increased protective efficacy
BackgroundWhile 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...
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1006716/full |
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| author | Natasha KC L. W. Preston Church Pouria Riyahi Sumana Chakravarty Robert A. Seder Judith E. Epstein Kirsten E. Lyke Benjamin Mordmüller Benjamin Mordmüller Peter G. Kremsner Peter G. Kremsner Mahamadou S. Sissoko Sara Healy Patrick E. Duffy Said A. Jongo Vicente Urbano Nsue Ndong Nchama Salim Abdulla Maxmillian Mpina Maxmillian Mpina Maxmillian Mpina Sodiomon B. Sirima 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_facet | Natasha KC L. W. Preston Church Pouria Riyahi Sumana Chakravarty Robert A. Seder Judith E. Epstein Kirsten E. Lyke Benjamin Mordmüller Benjamin Mordmüller Peter G. Kremsner Peter G. Kremsner Mahamadou S. Sissoko Sara Healy Patrick E. Duffy Said A. Jongo Vicente Urbano Nsue Ndong Nchama Salim Abdulla Maxmillian Mpina Maxmillian Mpina Maxmillian Mpina Sodiomon B. Sirima 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_sort | Natasha KC |
| collection | DOAJ |
| description | BackgroundWhile 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.MethodsUsing a standardized enzyme-linked immunosorbent assay, IgG antibodies to the major surface protein on Plasmodium falciparum (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).ResultsFemales ≥ 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.ConclusionImmunization 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. |
| first_indexed | 2024-04-10T00:50:10Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T00:50:10Z |
| publishDate | 2022-10-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-d6334f1741f1482b91e5bb9239e66e762023-03-13T11:47:46ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.10067161006716Increased levels of anti-PfCSP antibodies in post-pubertal females versus males immunized with PfSPZ Vaccine does not translate into increased protective efficacyNatasha KC0L. W. Preston Church1Pouria Riyahi2Sumana Chakravarty3Robert A. Seder4Judith E. Epstein5Kirsten E. Lyke6Benjamin Mordmüller7Benjamin Mordmüller8Peter G. Kremsner9Peter G. Kremsner10Mahamadou S. Sissoko11Sara Healy12Patrick E. Duffy13Said A. Jongo14Vicente Urbano Nsue Ndong Nchama15Salim Abdulla16Maxmillian Mpina17Maxmillian Mpina18Maxmillian Mpina19Sodiomon B. Sirima20Sodiomon B. Sirima21Matthew B. Laurens22Laura C. Steinhardt23Martina Oneko24MingLin Li25Tooba Murshedkar26Peter F. Billingsley27B. Kim Lee Sim28Thomas L. Richie29Stephen L. Hoffman30Sanaria Inc., Rockville, MD, United StatesSanaria Inc., Rockville, MD, United StatesSanaria Inc., Rockville, MD, United StatesSanaria Inc., Rockville, MD, United StatesVaccine Research Center, National Institute of Heath, Bethesda, MD, United StatesNaval Medical Research Center (NMRC), Silver Spring, MD, United StatesCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, United StatesInstitut für Tropenmedizin, Eberhard Karls Universität Tübingen and German Center for Infection Research, Tübingen, GermanyDepartment of Medical Microbiology, Radboud University Medical Center, Nijmegen, NetherlandsInstitut für Tropenmedizin, Eberhard Karls Universität Tübingen and German Center for Infection Research, Tübingen, GermanyCentre de Recherches Medicales de Lambaréné, Lambaréné, GabonMalaria 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, MaliLaboratory of Malaria Immunology and Parasitology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health (LMIV/NIAID/NIH), Rockville, MD, United StatesLaboratory of Malaria Immunology and Parasitology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health (LMIV/NIAID/NIH), Rockville, MD, United States0Bagamoyo Research and Training Centre, Ifakara Health Institute, Bagamoyo, Tanzania1Ministry of Health and Social Welfare, Malabo, Equatorial Guinea0Bagamoyo Research and Training Centre, Ifakara Health Institute, Bagamoyo, Tanzania0Bagamoyo Research and Training Centre, Ifakara Health Institute, Bagamoyo, Tanzania2Swiss Tropical Public Health Institute, Basel, Switzerland3University of Basel, Basel, Switzerland4Groupe de Recherche Action en Santé, Ouagadougou, Burkina Faso5Centre National de Recherche et de Formation sur le Paludisme, Ouagadougou, Burkina FasoCenter for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, United States6Malaria Branch, Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, GA, United States7Kenya Medical Research Institute, Centre for Global Health Research, Kisumu, KenyaSanaria Inc., Rockville, MD, United StatesSanaria Inc., Rockville, MD, United StatesSanaria Inc., Rockville, MD, United StatesSanaria Inc., Rockville, MD, United StatesSanaria Inc., Rockville, MD, United StatesSanaria Inc., Rockville, MD, United StatesBackgroundWhile 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.MethodsUsing a standardized enzyme-linked immunosorbent assay, IgG antibodies to the major surface protein on Plasmodium falciparum (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).ResultsFemales ≥ 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.ConclusionImmunization 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1006716/fullPfSPZ Vaccinemalaria vaccinePlasmodium falciparumPfCSPantibodieshumoral immunity |
| spellingShingle | Natasha KC L. W. Preston Church Pouria Riyahi Sumana Chakravarty Robert A. Seder Judith E. Epstein Kirsten E. Lyke Benjamin Mordmüller Benjamin Mordmüller Peter G. Kremsner Peter G. Kremsner Mahamadou S. Sissoko Sara Healy Patrick E. Duffy Said A. Jongo Vicente Urbano Nsue Ndong Nchama Salim Abdulla Maxmillian Mpina Maxmillian Mpina Maxmillian Mpina Sodiomon B. Sirima 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 Increased levels of anti-PfCSP antibodies in post-pubertal females versus males immunized with PfSPZ Vaccine does not translate into increased protective efficacy Frontiers in Immunology PfSPZ Vaccine malaria vaccine Plasmodium falciparum PfCSP antibodies humoral immunity |
| title | Increased levels of anti-PfCSP antibodies in post-pubertal females versus males immunized with PfSPZ Vaccine does not translate into increased protective efficacy |
| title_full | Increased levels of anti-PfCSP antibodies in post-pubertal females versus males immunized with PfSPZ Vaccine does not translate into increased protective efficacy |
| title_fullStr | Increased levels of anti-PfCSP antibodies in post-pubertal females versus males immunized with PfSPZ Vaccine does not translate into increased protective efficacy |
| title_full_unstemmed | Increased levels of anti-PfCSP antibodies in post-pubertal females versus males immunized with PfSPZ Vaccine does not translate into increased protective efficacy |
| title_short | Increased levels of anti-PfCSP antibodies in post-pubertal females versus males immunized with PfSPZ Vaccine does not translate into increased protective efficacy |
| title_sort | increased levels of anti pfcsp antibodies in post pubertal females versus males immunized with pfspz vaccine does not translate into increased protective efficacy |
| topic | PfSPZ Vaccine malaria vaccine Plasmodium falciparum PfCSP antibodies humoral immunity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1006716/full |
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