UNASSIGNED: The demonstrated clinical efficacy of a @entity8310 virus (rVSV) vaccine vector has stimulated the investigation of additional serologically distinct Vesiculovirus vectors as therapeutic and/or prophylactic vaccine vectors to combat emerging @entity1800 . Amongst these viral threats are encephalitic alphaviruses, Venezuelan and eastern equine encephalitic viruses ( @entity22146 , EEEV), which have demonstrated potential for natural disease outbreaks, yet no licensed vaccines are available in the event of an epidemic. Here we report rescue of recombinant @entity68866 (rISFV) from genomic cDNA as a potential new vaccine vector platform. The rISFV genome was modified to attenuate virulence and engineered to express @entity22146 and EEEV E2/E1 surface glycoproteins as vaccine antigens. A single dose of the rISFV vaccine vectors elicited neutralizing antibody responses and protected @entity19 from lethal @entity22146 and EEEV challenge at one month post-vaccination as well as lethal @entity22146 challenge at eight months post-vaccination. A mixture of rISFV vectors expressing @entity22146 and EEEV E2/E1 glycoproteins also provided durable, single-dose protection from lethal @entity22146 and EEEV challenge, demonstrating the potential for a multivalent vaccine formulation. These findings were paralleled in studies with an attenuated form of rVSV expressing @entity22146 E2/E1 glycoproteins. Both rVSV and rISFV vectors were attenuated using an approach which has demonstrated safety in @entity1 trials of an rVSV/ @entity2858 vaccine. @entity18186 based on either of these vaccine vector platforms may present a safe and effective approach to prevent alphavirus induced disease in @entity1 . IMPORTANCE: This work introduces rISFV as a novel vaccine vector platform that is serologically distinct and phylogenetically distant from VSV. The rISFV vector has been attenuated by an approach used for an rVSV vector that has demonstrated safety in clinical studies. The vaccine potential of the rISFV vector was investigated in a well-established alphavirus disease model. The findings indicate the feasibility of producing a safe, efficacious, multivalent vaccine against the encephalitic alphaviruses @entity22146 and EEEV, both of which can cause @entity66 . The work also demonstrates efficacy of an attenuated rVSV vector that has already demonstrated safety and immunogenicity in multiple @entity2858 Phase I clinical studies. The absence of serological cross-reactivity between rVSV and rISFV and their phylogenetic divergence within the Vesiculovirus genus indicates potential for two stand-alone vaccine vector platforms that could be used to target multiple bacterial and/or viral agents in successive immunization campaigns, or as heterologous prime-boost agents.

Recombinant XXXX and @entity8310 virus vaccine vectors provide durable, multivalent, single dose protection against lethal alphavirus challenge.

@entity1 :: ('9606', 'Species') :: ['humans', 'human'] @entity68866 :: ('290008', 'Species') :: ['Isfahan virus'] @entity66 :: ('MESH:D004194', 'Disease') :: ['fatal disease'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity2858 :: ('11676', 'Species') :: ['HIV-1'] @entity8310 :: ('MESH:D054243', 'Disease') :: ['recombinant vesicular stomatitis'] @entity18186 :: ('MESH:D014612', 'Chemical') :: ['Vaccines'] @entity1800 :: ('MESH:D014777', 'Disease') :: ['viral diseases'] @entity22146 :: ('11036', 'Species') :: ['VEEV']
@entity68866 :: (290008,Species) :: ['Isfahan virus']
