期刊
MALARIA JOURNAL
卷 21, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12936-022-04169-8
关键词
GMZ2; Cytokine; Memory B cells; P. falciparum; CHMI; Microarray
资金
- German Center for Infection Research [TTU03.801, TTU 03.702, TTU 03.703]
- Projekt DEAL
In a vaccine trial investigating the malaria vaccine candidate GMZ2, it was found that the GMZ2-specific antibody response increased after vaccination but was not correlated to protection. However, antibody responses to several Plasmodium falciparum antigens and the broadness of malaria-specific antibody response were significantly higher in protected study participants.
Background: Antibody and cellular memory responses following vaccination are important measures of immunogenicity. These immune markers were quantified in the framework of a vaccine trial investigating the malaria vaccine candidate GMZ2. Methods: Fifty Gabonese adults were vaccinated with two formulations (aluminum Alhydrogel and CAF01) of GMZ2 or a control vaccine (Verorab). Vaccine efficacy was assessed using controlled human malaria infection (CHMI) by direct venous inoculation of 3200 live Plasmodium falciparum sporozoites (PfSPZ Challenge). GMZ2-stimulated T and specific B-cell responses were estimated by flow cytometry before and after vaccination. Additionally, the antibody response against 212 P. falciparum antigens was estimated before CHMI by protein microarray. Results: Frequencies of pro- and anti-inflammatory CD4(+)T cells stimulated with the vaccine antigen GMZ2 as well as B cell profiles did not change after vaccination. IL-10-producing CD4(+) T cells and CD20(+) IgG(+) B cells were increased post-vaccination regardless of the intervention, thus could not be specifically attributed to any malaria vaccine regimen. In contrast, GMZ2-specific antibody response increased after the vaccination, but was not correlated to protection. Antibody responses to several P. falciparum blood and liver stage antigens (MSP1, MSP4, MSP8, PfEMP1, STARP) as well as the breadth of the malaria-specific antibody response were significantly higher in protected study participants. Conclusions: In lifelong malaria exposed adults, the main marker of protection against CHMI is a broad antibody pattern recognizing multiple stages of the plasmodial life cycle. Despite vaccination with GMZ2 using a novel formulation, expansion of the GMZ2-stimulated T cells or the GMZ2-specific B cell response was limited, and the vaccine response could not be identified as a marker of protection against malaria.
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