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Prepublished online as a Blood First Edition Paper on March 20, 2003; DOI 10.1182/blood-2003-01-0110.

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2003-01-0110v1
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Blood, 1 July 2003, Vol. 102, No. 1, pp. 223-228

IMMUNOBIOLOGY

Immunogenicity and protective efficacy of orally administered recombinant Lactococcus lactis expressing surface-bound HIV Env

Ke-Qin Xin, Yuka Hoshino, Yoshihiko Toda, Shizunobu Igimi, Yoshitsugu Kojima, Nao Jounai, Kenji Ohba, Akira Kushiro, Mayumi Kiwaki, Kenji Hamajima, Dennis Klinman, and Kenji Okuda

From the Department of Bacteriology, Yokohama City University School of Medicine, Yokohama, Japan; Food and Drug Administration of National Health Institute, and Yakult Central Institute for Microbiological Research, Tokyo, Japan; Center for Biologics Evaluation and Research, and US Food and Drug Administration, Bethesda, MD.

This study investigates whether genetically modified orally administered Lactococcus lactis (L lactis) could be used as an HIV vaccine. L lactis is immunogenic and extremely safe when delivered orally. We created a recombinant L lactis vector expressing the envelope protein of HIV on its cell surface. Oral immunization with this vector induced high levels of HIV-specific serum IgG and fecal IgA antibodies. Cell-mediated immune responses also were generated in both the regional lymph nodes and the spleen. Dendritic cells are readily infected by L lactis and appear to play a potential role in mediating the development of these immune responses. The protective efficacy of this vaccine strategy was demonstrated by challenging mice intraperitoneally with an HIV Env–expressing vaccinia virus. Their viral loads were 350-fold lower than those of control mice. These findings support the further development of L lactis–based HIV vaccines. (Blood. 2003; 102:223-228)


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