Menon Vinay, Kapulu Melissa C, Taylor Iona, Jewell Kerry, Li Yuanyuan, Hill Fergal, Long Carole A, Miura Kazutoyo, Biswas Sumi
Jenner Institute, University of Oxford, Oxford, United Kingdom.
IMAXIO, Lyon, France.
Front Immunol. 2018 Jan 19;8:1998. doi: 10.3389/fimmu.2017.01998. eCollection 2017.
A malaria transmission-blocking vaccine would be a critical tool in achieving malaria elimination and eradication. By using chimpanzee adenovirus serotype 63 and modified vaccinia virus Ankara viral vectored vaccines, we investigated whether incorporating two antigens into one vaccine would result in higher transmission-reducing activity than one antigen. We demonstrated that when Pfs25 was administered with other antigens Pfs28 or Pfs230C, either concurrently as a mixed vaccine or co-expressed as a dual-antigen vaccine, the antibody response in mice to each antigen was comparable to a monoantigen vaccine, without immunological interference. However, we found that the transmission-reducing activity (functional activity) of dual-antigen vaccines was not additive. Dual-antigen vaccines generally only elicited similar transmission-reducing activity to monoantigen vaccines and in one instance had lower transmission-reducing activity. We found that despite the lack of immunological interference of dual-antigen vaccines, they are still not as effective at blocking malaria transmission as Pfs25-IMX313, the current leading candidate for viral vectored vaccines. Pfs25-IMX313 elicited similar quality antibodies to dual-antigen vaccines, but higher antibody titers.
疟疾传播阻断疫苗将是实现疟疾消除和根除的关键工具。通过使用黑猩猩腺病毒63型和改良安卡拉痘苗病毒载体疫苗，我们研究了将两种抗原整合到一种疫苗中是否会比单一抗原产生更高的传播减少活性。我们证明，当Pfs25与其他抗原Pfs28或Pfs230C同时作为混合疫苗给药或作为双抗原疫苗共表达时，小鼠对每种抗原的抗体反应与单抗原疫苗相当，没有免疫干扰。然而，我们发现双抗原疫苗的传播减少活性（功能活性）并非相加性的。双抗原疫苗通常仅引发与单抗原疫苗相似的传播减少活性，且在一个实例中传播减少活性较低。我们发现，尽管双抗原疫苗缺乏免疫干扰，但它们在阻断疟疾传播方面仍不如Pfs25-IMX313有效，Pfs25-IMX313是目前病毒载体疫苗的领先候选者。Pfs25-IMX313引发的抗体质量与双抗原疫苗相似，但抗体滴度更高。
