Priming T-cell responses with recombinant measles vaccine vector in a heterologous prime-boost setting in non-human primates

Bolton, Diane L.; Santra, Sampa; Swett-Tapia, Cindy; Custers, Jerome; Song, Ki Duk; Balachandran, Harikrishnan; Mach, Linh; Naim, Hussein Y.; Kozlowski, Pamela A.; Lifton, Michelle A.; Goudsmit, Jaap; Letvin, Norman L.; Radošević, Katarina

doi:10.1016/j.vaccine.2012.06.029

Cited by 11 publications

(10 citation statements)

References 32 publications

(52 reference statements)

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“…Further, both conventional and plasmacytoid human DCs were shown to cross-present tumor antigens and activate tumor-specific CTLs after exposure to measles virus-infected tumor cells [53,54]. Bolton et al previously showed that a measles vaccine vector can be used to prime SIV Gag-specific T cells in macaques, which could be amplified by a heterologous adenovirus boost [55]. Taken together, these data indicate that measles vaccines can be utilized for induction and promotion of antigen-specific CD8 + T cell responses.…”

Section: Discussionmentioning

confidence: 99%

Measles Vaccines Designed for Enhanced CD8+ T Cell Activation

Busch

Kubon

Mayer

et al. 2020

Viruses

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Priming and activation of CD8 + T cell responses is crucial to achieve anti-viral and anti-tumor immunity. Live attenuated measles vaccine strains have been used successfully for immunization for decades and are currently investigated in trials of oncolytic virotherapy. The available reverse genetics systems allow for insertion of additional genes, including heterologous antigens. Here, we designed recombinant measles vaccine vectors for priming and activation of antigen-specific CD8 + T cells. For proof-of-concept, we used cytotoxic T lymphocyte (CTL) lines specific for the melanoma-associated differentiation antigen tyrosinase-related protein-2 (TRP-2), or the model antigen chicken ovalbumin (OVA), respectively. We generated recombinant measles vaccine vectors with TRP-2 and OVA epitope cassette variants for expression of the full-length antigen or the respective immunodominant CD8 + epitope, with additional variants mediating secretion or proteasomal degradation of the epitope. We show that these recombinant measles virus vectors mediate varying levels of MHC class I (MHC-I)-restricted epitope presentation, leading to activation of cognate CTLs, as indicated by secretion of interferon-gamma (IFNγ) in vitro. Importantly, the recombinant OVA vaccines also mediate priming of naïve OT-I CD8 + T cells by dendritic cells. While all vaccine variants can prime and activate cognate T cells, IFNγ release was enhanced using a secreted epitope variant and a variant with epitope strings targeted to the proteasome. The principles presented in this study will facilitate the design of recombinant vaccines to elicit CD8 + responses against pathogens and tumor antigens.

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Section: Discussionmentioning

confidence: 99%

Measles Vaccines Designed for Enhanced CD8+ T Cell Activation

Busch

Kubon

Mayer

et al. 2020

Viruses

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“…Alternatively, the aerosol route of administration is very effective in humans as a booster for the second MV immunization [38]. In a recent study that also used a vector based upon an attenuated measles virus strain, expressing SIV Gag, transgene immunity was found to be weak, but immunisation was carried out in pre-immune rhesus macaques, albeit in the absence of protective titres of measles neutralising antibodies [59]. That pre-existing immunity may have limited replication of attenuated vaccine virus resulting in low levels of transgene expression and immunogenicity.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity of a Recombinant Measles-HIV-1 Clade B Candidate Vaccine

Stebbings

Février

et al. 2012

PLoS ONE

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Live attenuated measles virus is one of the most efficient and safest vaccines available, making it an attractive candidate vector for a HIV/AIDS vaccine aimed at eliciting cell-mediated immune responses (CMI). Here we have characterized the potency of CMI responses generated in mice and non-human primates after intramuscular immunisation with a candidate recombinant measles vaccine carrying an HIV-1 insert encoding Clade B Gag, RT and Nef (MV1-F4). Eight Mauritian derived, MHC-typed cynomolgus macaques were immunised with 105 TCID50 of MV1-F4, four of which were boosted 28 days later with the same vaccine. F4 and measles virus (MV)-specific cytokine producing T cell responses were detected in 6 and 7 out of 8 vaccinees, respectively. Vaccinees with either M6 or recombinant MHC haplotypes demonstrated the strongest cytokine responses to F4 peptides. Polyfunctional analysis revealed a pattern of TNFα and IL-2 responses by CD4+ T cells and TNFα and IFNγ responses by CD8+ T cells to F4 peptides. HIV-specific CD4+ and CD8+ T cells expressing cytokines waned in peripheral blood lymphocytes by day 84, but CD8+ T cell responses to F4 peptides could still be detected in lymphoid tissues more than 3 months after vaccination. Anti-F4 and anti-MV antibody responses were detected in 6 and 8 out of 8 vaccinees, respectively. Titres of anti-F4 and MV antibodies were boosted in vaccinees that received a second immunisation. MV1-F4 carrying HIV-1 Clade B inserts induces robust boostable immunity in non-human primates. These results support further exploration of the MV1-F4 vector modality in vaccination strategies that may limit HIV-1 infectivity.

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“…The measles vector backbone was based on the Berna vaccine Edmonston Zagreb 19 strain (MVEZb; GenBank accession number HV542005.1), which constituted the measles component of the Triviraten Berna MMR vaccine (Schwarzer et al, 1998). The SIVgag transgene placed between the native P and M genes of rMVEZb2.SIVgag (Bolton et al, 2012) was digested with MluI and AatII and replaced by either the ORFs encoding the MuV-HN protein, the influenza virus HA protein or the RSV-F protein (Fig. 1).…”

Section: Methodsmentioning

confidence: 99%