A human Phase I/IIa malaria challenge trial of a polyprotein malaria vaccine

多蛋白疟疾疫苗的人体 I/IIa 期疟疾攻毒试验

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作者:David W Porter, Fiona M Thompson, Tamara K Berthoud, Claire L Hutchings, Laura Andrews, Sumi Biswas, Ian Poulton, Eric Prieur, Simon Correa, Rosalind Rowland, Trudie Lang, Jackie Williams, Sarah C Gilbert, Robert E Sinden, Stephen Todryk, Adrian V S Hill

Abstract

We examined the safety, immunogenicity and efficacy of a prime-boost vaccination regime involving two poxvirus malaria subunit vaccines, FP9-PP and MVA-PP, expressing the same polyprotein consisting of six pre-erythrocytic antigens from Plasmodium falciparum. Following safety assessment of single doses, 15 volunteers received a heterologous prime-boost vaccination regime and underwent malaria sporozoite challenge. The vaccines were safe but interferon-γ ELISPOT responses were low compared to other poxvirus vectors, despite targeting multiple antigens. There was no vaccine efficacy as measured by delay in time to parasitaemia. A number of possible explanations are discussed, including the very large insert size of the polyprotein transgene.

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