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Gul Ahmad, Weidong Zhang, Workineh Torben, Afzal Ahrorov, Raymond T. Damian, Roman F. Wolf, Gary L. White, David W. Carey, Pauline N. M. Mwinzi, Lisa Ganley-Leal, Ronald C. Kennedy, Afzal A. Siddiqui, Preclinical Prophylactic Efficacy Testing of Sm-p80–Based Vaccine in a Nonhuman Primate Model of Schistosoma mansoni Infection and Immunoglobulin G and E Responses to Sm-p80 in Human Serum Samples From an Area Where Schistosomiasis Is Endemic, The Journal of Infectious Diseases, Volume 204, Issue 9, 1 November 2011, Pages 1437–1449, https://doi.org/10.1093/infdis/jir545
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Abstract
The prophylactic efficacy of a schistosome antigen (Sm-p80) was tested in a nonhuman primate model, the baboon. Using a total of 28 baboons, different vaccination strategies were used including recombinant Sm-p80 protein formulated in Toll-like receptor 7 and Toll-like receptor 9 agonists, and DNA priming followed by boosting with protein plus adjuvants. Recombinant protein approaches provided levels of prophylactic efficacy of 52%–58%, whereas prime-boost approaches conferred 38%–47% protection in baboons. An appropriately balanced pro-inflammatory (T-helper 17 [Th17] and Th1) and anti-inflammatory (Th2) type of response was generated; the Th1 and Th17 types of immune responses appear to be indicative of increased prophylactic efficacy. Production and expression of several cytokines (interleukin 2 [IL-2], interferon γ, IL-12α, IL-1β, IL-6, and IL-22) were up-regulated in vaccinated animals. Human correlate studies revealed Sm-p80 reactivity with immunoglobulin G in human serum samples from schistosome-infected individuals. In addition, a complete lack of prevailing Sm-p80–specific immunoglobulin E in a high-risk or infected population was observed, thus minimizing the risk of hypersensitivity reaction following vaccination with Sm-p80 in humans. This study provided the proof of concept to move Sm-p80 forward into further preclinical development leading to human clinical trials.
- anti-inflammatory agents
- cytokine
- recombinant proteins
- aldesleukin
- hypersensitivity
- immune response
- antigens
- dna
- interferons
- papio
- primates
- schistosoma
- schistosomiasis
- vaccination
- vaccines
- immunoglobulin g
- immunoglobulin e
- interleukin-6
- schistosoma mansonii infection
- agonists
- toll-like receptor
- human leukocyte interferon
- interleukin-22
- serum specimen
- toll-like receptor 9