دورية
Preclinical Evaluation of the Safety and Immunogenicity of a Vaccine Consisting of Plasmodium falciparumLiver-Stage Antigen 1 with Adjuvant AS01B Administered Alone or Concurrently with the RTS,S/AS01B Vaccine in Rhesus Primates
| العنوان: | Preclinical Evaluation of the Safety and Immunogenicity of a Vaccine Consisting of Plasmodium falciparumLiver-Stage Antigen 1 with Adjuvant AS01B Administered Alone or Concurrently with the RTS,S/AS01B Vaccine in Rhesus Primates |
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| المؤلفون: | Pichyangkul, S., Kum-Arb, U., Yongvanitchit, K., Limsalakpetch, A., Gettayacamin, M., Lanar, D. E., Ware, L. A., Stewart, V. A., Heppner, D. G., Mettens, P., Cohen, J. D., Ballou, W. R., Fukuda, M. M. |
| المصدر: | Infection and Immunity; January 2008, Vol. 76 Issue: 1 p229-238, 10p |
| مستخلص: | ABSTRACTSeveral lines of evidence suggest that targeting pre-erythrocytic-stage parasites for malaria vaccine development can provide sterile immunity. The objectives of this study were (i) to evaluate preclinically the safety and immunogenicity of a new recombinant pre-erythrocytic-stage antigen, liver-stage antigen 1 (LSA1), in nonhuman primates; and (ii) to investigate the potential for immune interference between LSA1 and the leading malaria vaccine candidate, RTS,S, by comparing the immune responses after single-antigen vaccination to responses after simultaneous administration of both antigens at separate sites. Using a rhesus monkey model, we found that LSA1 formulated with the GlaxoSmithKline proprietary adjuvant system AS01B (LSA1/AS01B) was safe and immunogenic, inducing high titers of antigen-specific antibody and CD4+T-cell responses, as monitored by the production of interleukin-2 and gamma interferon, using intracellular cytokine staining. RTS,S/AS01B vaccination was well tolerated and demonstrated robust antibody and moderate CD4+T-cell responses to circumsporozoite protein (CSP) and HBsAg. Positive CD8+T-cell responses to HBsAg were detected, whereas the responses to CSP and LSA1 were negligible. For both LSA1/AS01B and RTS,S/AS01B, no statistically significant differences were observed between individual and concurrent administration in the magnitude or duration of antibody and T-cell responses. Our results revealed that both pre-erythrocytic-stage antigens were safe and immunogenic, administered either separately or simultaneously to rhesus monkeys, and that no significant immune cross interference occurred with concurrent separate-site administration. The comparison of the profiles of immune responses induced by separate-site and single-site vaccinations with LSA1 and RTS,S warrants further investigation. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 00199567 10985522 |
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| DOI: | 10.1128/IAI.00977-07 |