A PfRH5-based vaccine is efficacious against heterologous strain blood-stage Plasmodium falciparum infection in aotus monkeys
| Autor: | Cécile Crosnier, Alexandra J. Spencer, Luis A. Lugo-Roman, Kimberly A. Edgel, Kathryn A. Hjerrild, Lynn Lambert, Alexander D. Douglas, Kathryn H. Milne, Julio A. Ventocilla, Carmen Lucas, Joseph J. Illingworth, Jeromy T. Moorhead, Yimin Wu, Andres G. Lescano, G. Christian Baldeviano, A Turner, Gavin J. Wright, Simon J. Draper, Daniel G. W. Alanine, Carole A. Long, Kazutoyo Miura, Karina P. Leiva, S. Josefin Bartholdson, Ababacar Diouf |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Cancer Research
Antibodies Protozoan Heterologous Antigens Protozoan Immunity Heterologous Microbiology Article Antigen Neutralization Tests Immunity In vivo Immunology and Microbiology(all) Virology Malaria Vaccines parasitic diseases medicine Animals Molecular Biology biology Plasmodium falciparum biology.organism_classification medicine.disease Antibodies Neutralizing Malaria 3. Good health Bacterial adhesin Disease Models Animal Aotus trivirgatus biology.protein Female Parasitology Antibody Carrier Proteins |
| Zdroj: | Cell Host & Microbe |
| ISSN: | 1934-6069 1931-3128 |
| Popis: | Summary Antigenic diversity has posed a critical barrier to vaccine development against the pathogenic blood-stage infection of the human malaria parasite Plasmodium falciparum. To date, only strain-specific protection has been reported by trials of such vaccines in nonhuman primates. We recently showed that P. falciparum reticulocyte binding protein homolog 5 (PfRH5), a merozoite adhesin required for erythrocyte invasion, is highly susceptible to vaccine-inducible strain-transcending parasite-neutralizing antibody. In vivo efficacy of PfRH5-based vaccines has not previously been evaluated. Here, we demonstrate that PfRH5-based vaccines can protect Aotus monkeys against a virulent vaccine-heterologous P. falciparum challenge and show that such protection can be achieved by a human-compatible vaccine formulation. Protection was associated with anti-PfRH5 antibody concentration and in vitro parasite-neutralizing activity, supporting the use of this in vitro assay to predict the in vivo efficacy of future vaccine candidates. These data suggest that PfRH5-based vaccines have potential to achieve strain-transcending efficacy in humans. Graphical Abstract Highlights • Vaccines based on the P. falciparum merozoite antigen PfRH5 were tested in Aotus monkeys • PfRH5-based vaccines afforded protection against heterologous strains of P. falciparum • Protection correlated with anti-PfRH5 IgG concentration and in vivo neutralization Antigenic diversity has hindered development of vaccines against the pathogenic blood-stage of Plasmodium falciparum. Douglas et al. demonstrate that human-compatible PfRH5-based vaccines can protect Aotus monkeys against vaccine-heterologous P. falciparum challenge. Protection correlated with anti-PfRH5 antibody concentration and parasite-neutralizing activity. PfRH5-based vaccines have potential to achieve strain-transcending efficacy in humans. |
| Databáze: | OpenAIRE |
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