Chimeric virus-like particles and capsomeres induce similar CD8(+)T cell responses but differ in capacity to induce CD4(+)T cell responses and antibody responses

Pattinson, David J., Apte, Simon H., Wibowo, Nani, Rivera-Hernandez, Tania, Groves, Penny L., Middelberg, Anton P.J., and Doolan, Denise L. (2020) Chimeric virus-like particles and capsomeres induce similar CD8(+)T cell responses but differ in capacity to induce CD4(+)T cell responses and antibody responses. Frontiers in Immunology, 11. 564627.

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Abstract

Despite extensive research, the development of an effective malaria vaccine remains elusive. The induction of robust and sustained T cell and antibody response by vaccination is an urgent unmet need. Chimeric virus-like particles (VLPs) are a promising vaccine platform. VLPs are composed of multiple subunit capsomeres which can be rapidly produced in a cost-effective manner, but the ability of capsomeres to induce antigen-specific cellular immune responses has not been thoroughly investigated. Accordingly, we have compared chimeric VLPs and their sub-unit capsomeres for capacity to induce CD8(+)and CD4(+)T cell and antibody responses. We produced chimeric murine polyomavirus VLPs and capsomeres each incorporating defined CD8(+)T cell, CD4(+)T cell or B cell repeat epitopes derived fromPlasmodium yoeliiCSP. VLPs and capsomeres were evaluated using both homologous or heterologous DNA prime/boost immunization regimens for T cell and antibody immunogenicity. Chimeric VLP and capsomere vaccine platforms induced robust CD8(+)T cell responses at similar levels which was enhanced by a heterologous DNA prime. The capsomere platform was, however, more efficient at inducing CD4(+)T cell responses and less efficient at inducing antigen-specific antibody responses. Our data suggest that capsomeres, which have significant manufacturing advantages over VLPs, should be considered for diseases where a T cell response is the desired outcome.

Item ID: 64940
Item Type: Article (Research - C1)
ISSN: 1664-3224
Keywords: malaria, vaccine, T cells, virus-like particle, capsomere, murine polyomavirus, chimeric, Plasmodium yoelii
Copyright Information: Copyright © 2020 Pattinson, Apte, Wibowo, Rivera-Hernandez, Groves, Middelberg and Doolan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s)are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Funders: National Health and Medical Research Council (NHMRC), Australian Infectious Diseases Network (AIDN)
Projects and Grants: NHMRC grant no. 1037304, AIDN UQ-QIMR Seed grant, NHMRC Principal Research Fellowship #1023636
Date Deposited: 04 Nov 2020 07:44
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3207 Medical microbiology > 320704 Medical parasitology @ 100%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200104 Prevention of human diseases and conditions @ 100%
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