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Placenta-derived gp96 as a multivalent prophylactic cancer vaccine.

ABSTRACT: A major challenge for designing prophylactic cancer vaccines is to define immunogenic and safe cancer antigens. Given the striking similarity of antigen expression patterns between cancer and embryonic tissues, we defined a prototype strategy of using placenta-derived heat shock protein gp96, which induces prophylactic anti-tumor T cell responses. Immunization with placental gp96 provided partial protection and long-term (at least 3 months) anti-tumor immunity against growth of transplantable melanoma or breast tumors in mice, elicited total protection against 7, 12-dimethylbenz(a)-anthracene (DMBA)-induced mammary tumors in rats, and significantly reduced the occurrence and growth of autochthonous breast tumors in HER2 transgenic mice. Placental gp96 activated HER2- and MUC1-specific T cell responses through binding to tumor-associated antigens. Our results reveal the novel immunogenicity of placental gp96 and its potential use as a multivalent cancer vaccine.

SUBMITTER: Zhao B

PROVIDER: S-EPMC3674428 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Placenta-derived gp96 as a multivalent prophylactic cancer vaccine.

Zhao Bao B Wang Yanzhong Y Wu Bo B Liu Shan S Wu Erjie E Fan HongXia H Gui MingMing M Chen Lizhao L Li Changfei C Ju Ying Y Zhang Wei W Meng Songdong S

Scientific reports 20130101

A major challenge for designing prophylactic cancer vaccines is to define immunogenic and safe cancer antigens. Given the striking similarity of antigen expression patterns between cancer and embryonic tissues, we defined a prototype strategy of using placenta-derived heat shock protein gp96, which induces prophylactic anti-tumor T cell responses. Immunization with placental gp96 provided partial protection and long-term (at least 3 months) anti-tumor immunity against growth of transplantable me ...[more]

PMID: 23739295

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Project description:The search for a universal filovirus vaccine that provides protection against multiple filovirus species has been prompted by sporadic but highly lethal outbreaks of Ebolavirus and Marburgvirus infections. A good prophylactic vaccine should be able to provide protection to all known filovirus species and as an upside potentially protect from newly emerging virus strains. We investigated the immunogenicity and protection elicited by multivalent vaccines expressing glycoproteins (GP) from Ebola virus (EBOV), Sudan virus (SUDV), Taï Forest virus (TAFV) and Marburg virus (MARV). Immune responses against filovirus GP have been associated with protection from disease. The GP antigens were expressed by adenovirus serotypes 26 and 35 (Ad26 and Ad35) and modified Vaccinia virus Ankara (MVA) vectors, all selected for their strong immunogenicity and good safety profile. Using fully lethal NHP intramuscular challenge models, we assessed different vaccination regimens for immunogenicity and protection from filovirus disease. Heterologous multivalent Ad26-Ad35 prime-boost vaccination regimens could give full protection against MARV (range 75%-100% protection) and EBOV (range 50% to 100%) challenge, and partial protection (75%) against SUDV challenge. Heterologous multivalent Ad26-MVA prime-boost immunization gave full protection against EBOV challenge in a small cohort study. The use of such multivalent vaccines did not show overt immune interference in comparison with monovalent vaccines. Multivalent vaccines induced GP-specific antibody responses and cellular IFNγ responses to each GP expressed by the vaccine, and cross-reactivity to TAFV GP was detected in a trivalent vaccine expressing GP from EBOV, SUDV and MARV. In the EBOV challenge studies, higher humoral EBOV GP-specific immune responses (p = 0.0004) were associated with survival from EBOV challenge and less so for cellular immune responses (p = 0.0320). These results demonstrate that it is feasible to generate a multivalent filovirus vaccine that can protect against lethal infection by multiple members of the filovirus family.

Dataset Information

Placenta-derived gp96 as a multivalent prophylactic cancer vaccine.

Publications

Placenta-derived gp96 as a multivalent prophylactic cancer vaccine.

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