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Antibody-Dependent, Gamma Interferon-Independent Sterilizing Immunity Induced by a Subunit Malaria Vaccine.
Chawla, Bhavna; Mahajan, Babita; Oakley, Miranda; Majam, Victoria F; Belmonte, Arnel; Sedegah, Martha; Shimp, Richard L; Kaslow, David C; Kumar, Sanjai.
Afiliación
  • Chawla B; Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
  • Mahajan B; Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
  • Oakley M; Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
  • Majam VF; Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
  • Belmonte A; Naval Medical Research Center, Silver Spring, Maryland, USA.
  • Sedegah M; Naval Medical Research Center, Silver Spring, Maryland, USA.
  • Shimp RL; Laboratory of Malaria Immunology and Vaccinology, NIAID, NIH, Rockville, Maryland, USA.
  • Kaslow DC; PATH Essential Medicines, Seattle, Washington, USA.
  • Kumar S; Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA Sanjai.Kumar@fda.hhs.gov.
Infect Immun ; 87(10)2019 10.
Article en En | MEDLINE | ID: mdl-31308085
The development of effective malaria vaccines is hampered by incomplete understanding of the immunological correlates of protective immunity. Recently, the moderate clinical efficacy of the Plasmodium falciparum circumsporozoite protein (CSP)-based RTS,S/AS01E vaccine in phase 3 studies highlighted the urgency to design and test more efficacious next-generation malaria vaccines. In this study, we report that immunization with recombinant CSP from Plasmodium yoelii (rPyCSP), when delivered in Montanide ISA 51, induced sterilizing immunity against sporozoite challenge in C57BL/6 and BALB/c strains of mice. This immunity was antibody dependent, as evidenced by the complete loss of immunity in B-cell-knockout (KO) mice and by the ability of immune sera to neutralize sporozoite infectivity in mice. Th2-type isotype IgG1 antibody levels were associated with protective immunity. The fact that immunized gamma interferon (IFN-γ)-KO mice and wild-type (WT) mice have similar levels of protective immunity and the absence of IFN-γ-producing CD4+ and CD8+ T cells in protected mice, as shown by flow cytometry, indicate that the immunity is IFN-γ independent. Protection against sporozoite challenge correlated with higher frequencies of CD4+ T cells that express interleukin-2 (IL-2), IL-4, and tumor necrosis factor alpha (TNF-α). In the RTS,S study, clinical immunity was associated with higher IgG levels and frequencies of IL-2- and TNF-α-producing CD4+ T cells. The other hallmarks of immunity in our study included an increased number of follicular B cells but a loss in follicular T helper cells. These results provide an excellent model system to evaluate the efficacy of novel adjuvants and vaccine dosage and determine the correlates of immunity in the search for superior malaria vaccine candidates.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunoglobulina G / Anticuerpos Antiprotozoarios / Plasmodium yoelii / Proteínas Protozoarias / Vacunas contra la Malaria / Malaria Tipo de estudio: Prognostic_studies Idioma: En Revista: Infect Immun Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inmunoglobulina G / Anticuerpos Antiprotozoarios / Plasmodium yoelii / Proteínas Protozoarias / Vacunas contra la Malaria / Malaria Tipo de estudio: Prognostic_studies Idioma: En Revista: Infect Immun Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos