期刊
NPJ VACCINES
卷 7, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41541-022-00473-1
关键词
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资金
- German Federal Ministry of Education and Research (BMBF) through the German Center for Infection Research (DZIF)
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health under SBIR [5R44AI058375, 5R44AI055229]
This study tested two accelerated three-dose schedules for malaria vaccination and found that the 10-day regimen had better outcomes in inducing specific T cell and antibody responses. The shorter vaccination interval may lead to a longer exposure to liver-stage parasites, which contributes to a stronger immune response.
Repeated direct venous inoculation of Plasmodium falciparum sporozoites (PfSPZ) together with antimalarial chemoprophylaxis (PfSPZ-CVac) is the most potent way to induce sterile immunity against P. falciparum infection in malaria-naive volunteers. However, established schedules are complex and long. Here, we tested two accelerated three-dose schedules (28- and 10-day regimen) assessing efficacy by controlled human malaria infection (CHMI) against placebo, comparing vaccine-specific T cell and antibody responses by antigen-reactive T cell enrichment (ARTE) and protein microarray, respectively. Both regimens were similarly efficacious (67 and 63% vaccine efficacy) but different in the induction of vaccine-specific T cells and antibodies. The 10-day regimen resulted in higher numbers of antigen-specific CD4+ effector memory pro-inflammatory T cells and a broader antibody response compared with the 28-day regimen. Usually in nature, P. falciparum liver stage lasts about 6.5 days. The short vaccination-interval of the 10-day regimen prolongs the time of continuous exposure to liver-stage parasites, which may explain the stronger response. Besides dose and number of vaccinations, duration of liver-stage exposure is a factor to optimize PfSPZ-CVac immunogenicity.
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