| Autor: |
Forbes, Emily K., Biswas, Sumi, Collins, Katharine A., Gilbert, Sarah C., Hill, Adrian V. S., Draper, Simon J. |
| Jazyk: |
angličtina |
| Rok vydání: |
2011 |
| Předmět: |
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| Popis: |
Replication-deficient adenovirus and modified vaccinia virus Ankara (MVA) vectors expressing single pre-erythrocytic or blood-stage Plasmodium falciparum antigens have entered clinical testing using a heterologous prime-boost immunization approach. Here we investigated the utility of the same immunization regime when combining viral vectored vaccines expressing the 42kDa C-terminus of the blood-stage antigen merozoite surface protein 1 (MSP142) and the pre-erythrocytic antigen circumsporozoite protein (CSP) in the P. yoelii mouse model. We find that vaccine co-administration leads to maintained antibody responses and efficacy against blood-stage infection, but reduced secondary CD8+ T cell responses against both antigens and efficacy against liver-stage infection. CD8+ T cell interference can be minimized by co-administering the MVA vaccines at separate sites, resulting in enhanced liver-stage efficacy in mice immunized against both antigens compared to just one. CD8+ T cell interference (following MVA co-administration as a mixture) may partly be caused by a lack of physiological space for high magnitude responses against multiple antigens, but is not caused by competition for presentation of antigen on MHC class I molecules, nor is it due to restricted T cell access to APCs presenting both antigens. Instead, enhanced killing of peptide-pulsed cells is observed in mice possessing pre-existing T cells against two antigens, in comparison to just one, suggesting priming against multiple antigens may in part reduce the potency of multi-antigen MVA vectors to stimulate secondary CD8+ T cell responses. These data have important implications for the development of a multi-stage or multi-component viral vectored malaria vaccine for use in humans. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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