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Recombinant Semliki Forest virus particles encoding the prME or NS1 proteins of louping ill virus protect mice from
Abstract:
Recombinant Semliki Forest virus (rSFV) vaccines encoding louping ill virus (LIV) genes prME and NS1 were examined. Cells transfected with rSFV-prME RNA showed correct processing of the precursor prME and the release into the medium of M and E proteins in particulate form, whilst rSFV-NS1-transfected cells secreted glycosylated, heat-labile NS1 dimers. Mice immunized with rSFV particles produced antibodies against prME and NS1 that were mainly of the IgG2a subtype, indicating that a T-helper 1 immune response was induced. Immunization with prME- or NS1-encoding particles induced T-cell proliferation. Mice vaccinated intraperitoneally (i.p.) with rSFV-prME and/or rSFV-NS1 were significantly protected from lethal i.p. challenge by two strains of LIV, the virulent LI/31 strain, from which the commercial LIV vaccine is derived, and the less-virulent LI/I antibody-escape variant. Intranasal (i.n.) vaccination was protective for rSFV-prME only against LI/31 challenge and not against challenge with LI/I. Immunization with rSFV-NS1 was protective against i.p. and i.n. challenge with both virus strains when given i.p., but was not protective when given i.n. For unvaccinated mice infected with LIV, all animals showing clinical signs had severe degenerative and inflammatory lesions in the central nervous system. None of the rSFV-vaccinated mice that survived challenge showed central nervous system pathology, with the exception of mild leptomeningitis in a minority of LI/31-infected mice. This suggests that protection following immunization with rSFV must occur at early stages of LIV infection.
Insights
Recombinant Semliki Forest virus (rSFV) vaccines expressing louping ill virus (LIV) genes prME and NS1 effectively protected mice against LIV challenge. This rSFV vaccination induced a T-helper 1 immune response and prevented central nervous system pathology.
Area of Science:
- Veterinary Virology
- Vaccine Development
- Immunology
Background:
- Louping ill virus (LIV) is a significant tick-borne pathogen affecting livestock.
- Current vaccines exist, but novel approaches are being explored.
- Recombinant Semliki Forest virus (rSFV) is a potential vector for vaccine delivery.
Purpose of the Study:
- To evaluate the efficacy of rSFV vaccines encoding LIV prME and NS1 genes.
- To assess the immune response induced by these rSFV vaccines.
- To determine the protective potential against virulent and antibody-escape LIV strains.
Main Methods:
- Construction and transfection of rSFV encoding LIV prME and NS1 genes.
- Analysis of protein processing and release in transfected cells.
- Immunization of mice with rSFV particles.
- Assessment of antibody and T-cell responses.
- Challenge studies with virulent (LI/31) and antibody-escape (LI/I) LIV strains via intraperitoneal and intranasal routes.
Main Results:
- rSFV-prME and rSFV-NS1 vaccines induced IgG2a antibodies and T-cell proliferation, indicating a T-helper 1 response.
- Intraperitoneal vaccination with rSFV-prME and/or rSFV-NS1 conferred significant protection against lethal LIV challenge.
- Intranasal vaccination showed partial protection, with rSFV-prME effective only against the virulent strain.
- rSFV-NS1 given intraperitoneally protected against both intranasal and intraperitoneal challenge.
- Vaccinated survivors showed minimal to no central nervous system pathology.
Conclusions:
- rSFV-based vaccines encoding LIV prME and NS1 are effective in inducing protective immunity.
- The induced immune response is primarily T-helper 1 biased.
- Protection appears to be mediated by early-stage control of LIV infection.
- rSFV vectors show promise for developing novel LIV vaccines.