[HTML][HTML] New adenovirus-based vaccine vectors targeting Pfs25 elicit antibodies that inhibit Plasmodium falciparum transmission
KA McGuire, K Miura, CM Wiethoff, KC Williamson - Malaria Journal, 2017 - Springer
KA McGuire, K Miura, CM Wiethoff, KC Williamson
Malaria Journal, 2017•SpringerBackground An effective malaria transmission-blocking vaccine (TBV) would be a major
advance in the current efforts to eliminate and, ultimately, eradicate malaria. Antibodies
against Plasmodium falciparum surface protein, Pfs25, are known to block parasite
development in the mosquito vector. However, in initial clinical trials the limited
immunogenicity of recombinant Pfs25 protein-in-adjuvant vaccines has been a challenge.
Methods Novel human adenovirus type 5 (Ad5) vectors were used in heterologous prime …
advance in the current efforts to eliminate and, ultimately, eradicate malaria. Antibodies
against Plasmodium falciparum surface protein, Pfs25, are known to block parasite
development in the mosquito vector. However, in initial clinical trials the limited
immunogenicity of recombinant Pfs25 protein-in-adjuvant vaccines has been a challenge.
Methods Novel human adenovirus type 5 (Ad5) vectors were used in heterologous prime …
Background
An effective malaria transmission-blocking vaccine (TBV) would be a major advance in the current efforts to eliminate and, ultimately, eradicate malaria. Antibodies against Plasmodium falciparum surface protein, Pfs25, are known to block parasite development in the mosquito vector. However, in initial clinical trials the limited immunogenicity of recombinant Pfs25 protein-in-adjuvant vaccines has been a challenge.
Methods
Novel human adenovirus type 5 (Ad5) vectors were used in heterologous prime boost vaccination strategies to augment the immune response against Pfs25. Specifically, an Ad5 vector that directs expression of full-length, membrane-bound Pfs25 was used as a priming immunization followed by a boost with Ad5 viral particles displaying only the Pfs25 epitope targeted by transmission-blocking antibodies 4B7 and 1D2 (Pfs25 aa 122–134) in hypervariable region 5 of the hexon capsid protein.
Results
This heterologous prime-boost vaccine strategy induced antibodies that significantly inhibit P. falciparum transmission to mosquitoes in a standard membrane-feeding assay. Further, immunized mice generated a robust anti-Pfs25 antibody response characterized by higher titer, higher relative avidity and a broader IgG subclass profile than observed with a homologous prime-boost with recombinant Pfs25/alum.
Conclusion
The data suggest that focusing the immune response against defined epitopes displayed on the viral capsid is an effective strategy for transmission-blocking vaccine development.
Springer
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