Open Access Short report

Prior exposure to an attenuated Listeria vaccine does not reduce immunogenicity: pre-clinical assessment of the efficacy of a Listeria vaccine in the induction of immune responses against HIV

James B Whitney12*, Saied Mirshahidi3, So-Yon Lim12, Lauren Goins24, Chris C Ibegbu5, Daniel C Anderson5, Richard B Raybourne6, Fred R Frankel7, Judy Lieberman28 and Ruth M Ruprecht24

Author Affiliations

1 Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA

2 Harvard Medical School, Boston, MA, 02115 USA

3 Loma Linda University Cancer Center, Loma Linda, CA 92354, USA

4 Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115 USA

5 Division of Research Resources and Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329 USA

6 Immunobiology Branch, Center for Food Safety and Applied Nutrition, Food and Drug Administration, Laurel, MD 20708 USA

7 Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104 USA

8 The Immune Disease Institute and Program in Cellular and Molecular Medicine Children's Hospital Boston, Department of Pediatrics MA 02115 USA

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Journal of Immune Based Therapies and Vaccines 2011, 9:2  doi:10.1186/1476-8518-9-2

Published: 18 January 2011

Abstract

Background

We have evaluated an attenuated Listeria monocytogenes (Lm) candidate vaccine vector in nonhuman primates using a delivery regimen relying solely on oral vaccination. We sought to determine the impact of prior Lm vector exposure on the development of new immune responses against HIV antigens.

Findings

Two groups of rhesus macaques one Lm naive, the other having documented prior Lm vector exposures, were evaluated in response to oral inoculations of the same vector expressing recombinant HIV-1 Gag protein. The efficacy of the Lm vector was determined by ELISA to assess the generation of anti-Listerial antibodies; cellular responses were measured by HIV-Gag specific ELISpot assay. Our results show that prior Lm exposures did not diminish the generation of de novo cellular responses against HIV, as compared to Listeria-naïve monkeys. Moreover, empty vector exposures did not elicit potent antibody responses, consistent with the intracellular nature of Lm.

Conclusions

The present study demonstrates in a pre-clinical vaccine model, that prior oral immunization with an empty Lm vector does not diminish immunogenicity to Lm-expressed HIV genes. This work underscores the need for the continued development of attenuated Lm as an orally deliverable vaccine.