Oral immunization with a live coxsackievirus/HIV recombinant induces gag p24-specific T cell responses.
The development of an HIV/AIDS vaccine has proven to be elusive. Because human vaccine trials have not yet demonstrated efficacy, new vaccine strategies are needed for the HIV vaccine pipeline. We have been developing a new HIV vaccine platform using a live enterovirus, coxsackievirus B4 (CVB4) vect...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-09-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2932689?pdf=render |
| _version_ | 1819261964339118080 |
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| author | Rui Gu Anae Shampang Toufic Nashar Manisha Patil Deborah H Fuller Arlene I Ramsingh |
| author_facet | Rui Gu Anae Shampang Toufic Nashar Manisha Patil Deborah H Fuller Arlene I Ramsingh |
| author_sort | Rui Gu |
| collection | DOAJ |
| description | The development of an HIV/AIDS vaccine has proven to be elusive. Because human vaccine trials have not yet demonstrated efficacy, new vaccine strategies are needed for the HIV vaccine pipeline. We have been developing a new HIV vaccine platform using a live enterovirus, coxsackievirus B4 (CVB4) vector. Enteroviruses are ideal candidates for development as a vaccine vector for oral delivery, because these viruses normally enter the body via the oral route and survive the acidic environment of the stomach.We constructed a live coxsackievirus B4 recombinant, CVB4/p24(73(3)), that expresses seventy-three amino acids of the gag p24 sequence (HXB2) and assessed T cell responses after immunization of mice. The CVB4 recombinant was physically stable, replication-competent, and genetically stable. Oral or intraperitoneal immunization with the recombinant resulted in strong systemic gag p24-specific T cell responses as determined by the IFN-gamma ELISPOT assay and by multiparameter flow cytometry. Oral immunization with CVB4/p24(73(3)) resulted in a short-lived, localized infection of the gut without systemic spread. Because coxsackieviruses are ubiquitous in the human population, we also evaluated whether the recombinant was able to induce gag p24-specific T cell responses in mice pre-immunized with the CVB4 vector. We showed that oral immunization with CVB4/p24(73(3)) induced gag p24-specific immune responses in vector-immune mice.The CVB4/p24(73(3)) recombinant retained the physical and biological characteristics of the parental CVB4 vector. Oral immunization with the CVB4 recombinant was safe and resulted in the induction of systemic HIV-specific T cell responses. Furthermore, pre-existing vector immunity did not preclude the development of gag p24-specific T cell responses. As the search continues for new vaccine strategies, the present study suggests that live CVB4/HIV recombinants are potential new vaccine candidates for HIV. |
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| language | English |
| last_indexed | 2024-12-23T19:50:10Z |
| publishDate | 2010-09-01 |
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| spelling | doaj.art-339ecbe3e108401689302a51d34c4f8e2022-12-21T17:33:24ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-09-015910.1371/journal.pone.0012499Oral immunization with a live coxsackievirus/HIV recombinant induces gag p24-specific T cell responses.Rui GuAnae ShampangToufic NasharManisha PatilDeborah H FullerArlene I RamsinghThe development of an HIV/AIDS vaccine has proven to be elusive. Because human vaccine trials have not yet demonstrated efficacy, new vaccine strategies are needed for the HIV vaccine pipeline. We have been developing a new HIV vaccine platform using a live enterovirus, coxsackievirus B4 (CVB4) vector. Enteroviruses are ideal candidates for development as a vaccine vector for oral delivery, because these viruses normally enter the body via the oral route and survive the acidic environment of the stomach.We constructed a live coxsackievirus B4 recombinant, CVB4/p24(73(3)), that expresses seventy-three amino acids of the gag p24 sequence (HXB2) and assessed T cell responses after immunization of mice. The CVB4 recombinant was physically stable, replication-competent, and genetically stable. Oral or intraperitoneal immunization with the recombinant resulted in strong systemic gag p24-specific T cell responses as determined by the IFN-gamma ELISPOT assay and by multiparameter flow cytometry. Oral immunization with CVB4/p24(73(3)) resulted in a short-lived, localized infection of the gut without systemic spread. Because coxsackieviruses are ubiquitous in the human population, we also evaluated whether the recombinant was able to induce gag p24-specific T cell responses in mice pre-immunized with the CVB4 vector. We showed that oral immunization with CVB4/p24(73(3)) induced gag p24-specific immune responses in vector-immune mice.The CVB4/p24(73(3)) recombinant retained the physical and biological characteristics of the parental CVB4 vector. Oral immunization with the CVB4 recombinant was safe and resulted in the induction of systemic HIV-specific T cell responses. Furthermore, pre-existing vector immunity did not preclude the development of gag p24-specific T cell responses. As the search continues for new vaccine strategies, the present study suggests that live CVB4/HIV recombinants are potential new vaccine candidates for HIV.http://europepmc.org/articles/PMC2932689?pdf=render |
| spellingShingle | Rui Gu Anae Shampang Toufic Nashar Manisha Patil Deborah H Fuller Arlene I Ramsingh Oral immunization with a live coxsackievirus/HIV recombinant induces gag p24-specific T cell responses. PLoS ONE |
| title | Oral immunization with a live coxsackievirus/HIV recombinant induces gag p24-specific T cell responses. |
| title_full | Oral immunization with a live coxsackievirus/HIV recombinant induces gag p24-specific T cell responses. |
| title_fullStr | Oral immunization with a live coxsackievirus/HIV recombinant induces gag p24-specific T cell responses. |
| title_full_unstemmed | Oral immunization with a live coxsackievirus/HIV recombinant induces gag p24-specific T cell responses. |
| title_short | Oral immunization with a live coxsackievirus/HIV recombinant induces gag p24-specific T cell responses. |
| title_sort | oral immunization with a live coxsackievirus hiv recombinant induces gag p24 specific t cell responses |
| url | http://europepmc.org/articles/PMC2932689?pdf=render |
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