Oral immunization with a live coxsackievirus/HIV recombinant induces gag p24-specific T cell responses.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Gu
Rui
R
Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, New York, United States of America.
Shampang
Anae
A
Nashar
Toufic
T
Patil
Manisha
M
Fuller
Deborah H
DH
Ramsingh
Arlene I
AI
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D029822:Enterovirus B, Human / Q000235:genetics / Q000276:immunology*; D005260:Female; D016655:HIV Core Protein p24 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D006801:Humans; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D016655:HIV Core Protein p24; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; C514799:p24 protein, Human Immunodeficiency Virus Type 1
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