Abstract
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.
Highlights
Malaria is a parasitic disease with devastating global health consequences
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
Summary
Malaria incidence is estimated at 214 million cases per year, and mortality has been estimated at 438,000 deaths per year [1]. There is a critical need for effective malaria vaccines, especially with new global ambitions for malaria elimination and eradication [2], and the decreasing efficacy of existing malaria control interventions due to drug and insecticide resistance [3, 4]. More effective second-generation vaccines are urgently needed especially those which reduce transmission and incidence, rather than reducing morbidity and mortality [7]. Transmission-blocking vaccines (TBVs) are widely considered an essential tool for malaria elimination, either on their own or as components of a multistage vaccine or other control interventions [8, 9]. TBVs elicit antibodies that target sexual-stage antigens of the Plasmodium parasite or mosquito antigens when taken up by the mosquito, thereby blocking parasite development and preventing
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