Induction of Immune Responses in Mice and Monkeys to Ebola Virus after Immunization with Liposome-Encapsulated Irradiated Ebola Virus: Protection in Mice Requires CD4 ⁺ T Cells

Abstract

Ebola Zaire virus (EBO-Z

Induction of Humoral and CD8+ T Cell Responses Are Required for Protection against Lethal Ebola Virus Infection

“…eVLP-vaccinated BALB/c mice generated GP-specific CD8 ϩ responses to a single epitope from amino acids 161-169 (20,37), whereas C57BL/6 mice generated both CD4 ϩ and CD8 ϩ T cells specific for a single amino acid sequence within GP 531-545 . Interestingly, this CD4/CD8 stimulatory peptide WIPYFGPAAEGIYTE contains the putative fusion peptide sequence in the GP2 portion of the EBOV GP (41).…”

“…These findings provide evidence that VLP vaccination does not provide sterilizing immunity in mice given that novel immune responses to proteins beyond those used for vaccination are generated following challenge. Several other vaccine strategies have been shown to induce CTL responses against EBOV-specific GP and/or NP in mice, including several epitopes previously identified either before or following EBOV challenge (20,(23)(24)(25). The importance of CTL responses was demonstrated by transfer of NPspecific T cells to naive mice, which was sufficient to protect the recipient mice against lethal EBOV infection (23).…”

“…Specific CD8 ϩ T cell responses were detected in eVLP-vaccinated BALB/c and C57BL/6 mice using IFN-␥ production as a marker (Table I). In BALB/c mice, a GP-specific CD8 ϩ response was generated to the amino acid sequence LYDRLASTV (GP 161-169 ), a sequence that was previously described by Rao et al (20,37). A response to GP 161-169 in a representative set of mice is shown in Fig.…”

“…For EBOV, several vaccine strategies including liposomes encapsulating inactivated EBOV, DNA alone, DNA prime/adenovirus boost, and alphavirus replicon vaccines induce CTL responses against EBOV-specific epitopes of GP and/or nucleoprotein (NP) in mice (20,(23)(24)(25)(26). The importance of CTL responses was further demonstrated by successful adoptive transfer of NP-specific CTLs (23).…”

Status and challenges of filovirus vaccines

“…inoculation of the virus, the mouse model is not considered ideal for studies of the human disease. Mice have, however, been used as a tool for studying innate immunity, screening vaccine candidates, and elucidating protective epitopes for humoral and cellular immunity to ZEBOV [49][50][51][52][53][54][55][56][57][58].…”