Oral immunization with a recombinant Lactococcus lactis expressing HIV-1 antigen on GAS pilus induces strong mucosal immunity in the gut
| Autor: | Chamcha, Venkateswarlu, Jones, Andrew, Quigley, Bernard R., Scott, June R., Amara, Rama Rao |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Mice
Inbred BALB C Streptococcus pyogenes viruses Recombinant Fusion Proteins CD8-Positive T-Lymphocytes HIV Antibodies gag Gene Products Human Immunodeficiency Virus Article Lactococcus lactis Mice Peyer's Patches Bacterial Proteins Fimbriae Bacterial HIV-1 bacteria Animals Female Immunization Immunity Mucosal |
| Popis: | The induction of a potent humoral and cellular immune response in mucosal tissue is important for the development of an effective HIV vaccine. Most of the current HIV vaccines under development use the intramuscular route for immunization, which is relatively poor in generating potent and long-lived mucosal immune responses. Here, we explore the ability of an oral vaccination with a probiotic organism, Lactococcus lactis (L. lactis), to elicit HIV-specific immune responses in the mucosal and systemic compartments of BALB/c mice. We expressed the HIV-1 Gag-p24 on the tip of the T3 pilus of Streptococcus pyogenes as a fusion to the Cpa protein (LL-Gag). Following four monthly LL-Gag oral immunizations we observed strong Gag-specific IgG and IgA responses in serum, feces, and vaginal secretions. However, the Gag-specific CD8 T cell responses in the blood were at or below our detection limit. Following an intramuscular modified vaccinia Ankara (MVA)/Gag boost, we observed a robust Gag-specific CD8 T cell responses both in systemic and mucosal tissue, including intraepithelial and lamina propria lymphocytes of the small intestine, Peyer's patches, and mesenteric lymph nodes. Consistent with strong immunogenicity, the LL-Gag induced activation of CD11c+ CD11b+ dendritic cells in the Peyer's patches after oral immunization. Our results demonstrate that oral immunization with L. lactis expressing an antigen on the tip of the Group-A streptococcus pilus serves as an excellent vaccine platform to induce strong mucosal humoral and cellular immunity against HIV. |
| Databáze: | OpenAIRE |
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