Comparative studies of the capsid precursor polypeptide P1 and the capsid protein VP1 cDNA vectors for DNA vaccination against foot‐and‐mouth disease virus

Abstract

This strategy of using the whole capsid precursor protein P1 cDNA for vaccination, intentionally without the use of virus-specific protease or other encoding genes for safety reasons, may thus be employed as a relevant experimental system for induction or upgrading of effective neutralizing antibody response, and as a convenient surrogate test system for DNA vaccination studies of FMDV and presumably other viral diseases.

Immunization of DNA vaccine encoding C3d-VP1 fusion enhanced protective immune response against foot-and-mouth disease virus

“…Furthermore, VP1 DNA immunization could not provide protection in FMDV challenge experiment in mice [11]. The proposed reason was that the loop of VP1 in the naturally occurring virus could display multiple conformations and thus elicit a different population of antibodies during the immune responses [11,36,37]. In order to improve the immunity of DNA vaccine, the complete gene cassette P1-2A-3C-3D encoding the whole ''empty capsid'' was used and the results demonstrated that the capsid gene cassette conferred a good protection against viral challenge.…”

“…Unfortunately, although VP1 indeed elicited antibody response shown by previous reports and this study, the level of neutralizing antibodies in comparison was low [36] or under the detectable levels. Furthermore, VP1 DNA immunization could not provide protection in FMDV challenge experiment in mice [11]. The proposed reason was that the loop of VP1 in the naturally occurring virus could display multiple conformations and thus elicit a different population of antibodies during the immune responses [11,36,37].…”

“…In order to improve the immunity of DNA vaccine, the complete gene cassette P1-2A-3C-3D encoding the whole ''empty capsid'' was used and the results demonstrated that the capsid gene cassette conferred a good protection against viral challenge. However, there is a safety consideration that the authentic viral capsid might be beneficial to virus recombination in the host at the virus assembly level [11]. Therefore, we explored the possibility to improve the immunity of VP1 DNA by using molecular adjuvant C3d.…”

“…In contrast, DNA vaccine expressing the whole capsid precursor protein P1 or its extension P1-2A-3C-3D containing the complete ''empty capsid'' gene cassette could provide better protection [11,12]. However there is a safety consideration of virus recombination to make use of the whole capsid precursor protein DNA vaccine [11]. The alternative strategies are utilized to enhance the immune response of VP1 or the epitope combinations by using immunoglobulin heavy chain tag [12], gene fusion to ubiquitin [10], CpG [13], IL-1 and IL-2 [14,15], and IFN-c [16].…”

“…The DNA encoding the major viral antigen VP1, a capsid protein with critical determinants for infection and immunity failed to elicit high level of neutralization antibody and efficient protection either. In contrast, DNA vaccine expressing the whole capsid precursor protein P1 or its extension P1-2A-3C-3D containing the complete ''empty capsid'' gene cassette could provide better protection [11,12]. However there is a safety consideration of virus recombination to make use of the whole capsid precursor protein DNA vaccine [11].…”