Interplay of Cytokines and Adjuvants in the Regulation of Mucosal and Systemic HIV-Specific CTL
We examined the interplay between cytokines and adjuvants to optimize the induction of CTL by a mucosal HIV peptide vaccine. We show synergy between IL-12 and GM-CSF when administered together with the HIV peptide PCLUS3-18IIIB and cholera toxin (CT) in the induction of CTL activity and protection a...
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Published in | The Journal of immunology (1950) Vol. 165; no. 11; pp. 6454 - 6462 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
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United States
Am Assoc Immnol
01.12.2000
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Abstract | We examined the interplay between cytokines and adjuvants to optimize the induction of CTL by a mucosal HIV peptide vaccine. We show synergy between IL-12 and GM-CSF when administered together with the HIV peptide PCLUS3-18IIIB and cholera toxin (CT) in the induction of CTL activity and protection against mucosal viral transmission. Further, we examine the efficacy of mutant Escherichia coli labile toxin, LT(R192G), as a less toxic adjuvant than CT. LT(R192G) was as effective as or more effective than CT at inducing a mucosal CTL response. Moreover, LT(R192G) was as effective without IL-12 as CT was when combined with IL-12, and the response elicited by LT(R192G) with the vaccine was not further enhanced by the addition of IL-12. GM-CSF synergized with LT(R192G) without exogenous IL-12. Therefore, LT(R192G) may induce a more favorable cytokine response by not inhibiting IL-12 production. In particular, less IL-4 is made after LT(R192G) than CT immunization, and the response is less susceptible to anti-IL-12 inhibition. Thus, the choice of mucosal adjuvant affects the cytokine environment, and the mucosal response and protection can be enhanced by manipulating the cytokine environment with synergistic cytokine combinations incorporated in the vaccine. |
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AbstractList | We examined the interplay between cytokines and adjuvants to optimize the induction of CTL by a mucosal HIV peptide vaccine. We show synergy between IL-12 and GM-CSF when administered together with the HIV peptide PCLUS3-18IIIB and cholera toxin (CT) in the induction of CTL activity and protection against mucosal viral transmission. Further, we examine the efficacy of mutant Escherichia coli labile toxin, LT(R192G), as a less toxic adjuvant than CT. LT(R192G) was as effective as or more effective than CT at inducing a mucosal CTL response. Moreover, LT(R192G) was as effective without IL-12 as CT was when combined with IL-12, and the response elicited by LT(R192G) with the vaccine was not further enhanced by the addition of IL-12. GM-CSF synergized with LT(R192G) without exogenous IL-12. Therefore, LT(R192G) may induce a more favorable cytokine response by not inhibiting IL-12 production. In particular, less IL-4 is made after LT(R192G) than CT immunization, and the response is less susceptible to anti-IL-12 inhibition. Thus, the choice of mucosal adjuvant affects the cytokine environment, and the mucosal response and protection can be enhanced by manipulating the cytokine environment with synergistic cytokine combinations incorporated in the vaccine. Abstract We examined the interplay between cytokines and adjuvants to optimize the induction of CTL by a mucosal HIV peptide vaccine. We show synergy between IL-12 and GM-CSF when administered together with the HIV peptide PCLUS3–18IIIB and cholera toxin (CT) in the induction of CTL activity and protection against mucosal viral transmission. Further, we examine the efficacy of mutant Escherichia coli labile toxin, LT(R192G), as a less toxic adjuvant than CT. LT(R192G) was as effective as or more effective than CT at inducing a mucosal CTL response. Moreover, LT(R192G) was as effective without IL-12 as CT was when combined with IL-12, and the response elicited by LT(R192G) with the vaccine was not further enhanced by the addition of IL-12. GM-CSF synergized with LT(R192G) without exogenous IL-12. Therefore, LT(R192G) may induce a more favorable cytokine response by not inhibiting IL-12 production. In particular, less IL-4 is made after LT(R192G) than CT immunization, and the response is less susceptible to anti-IL-12 inhibition. Thus, the choice of mucosal adjuvant affects the cytokine environment, and the mucosal response and protection can be enhanced by manipulating the cytokine environment with synergistic cytokine combinations incorporated in the vaccine. |
Author | Belyakov, Igor M Clements, John D Berzofsky, Jay A Ahlers, Jeffrey D Strober, Warren |
Author_xml | – sequence: 1 fullname: Belyakov, Igor M – sequence: 2 fullname: Ahlers, Jeffrey D – sequence: 3 fullname: Clements, John D – sequence: 4 fullname: Strober, Warren – sequence: 5 fullname: Berzofsky, Jay A |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/11086085$$D View this record in MEDLINE/PubMed |
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Snippet | We examined the interplay between cytokines and adjuvants to optimize the induction of CTL by a mucosal HIV peptide vaccine. We show synergy between IL-12 and... Abstract We examined the interplay between cytokines and adjuvants to optimize the induction of CTL by a mucosal HIV peptide vaccine. We show synergy between... |
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SubjectTerms | 3T3 Cells Adjuvants, Immunologic - administration & dosage Adjuvants, Immunologic - physiology Administration, Rectal AIDS Vaccines - administration & dosage AIDS Vaccines - chemical synthesis AIDS Vaccines - immunology Amino Acid Sequence Animals Cytokines - administration & dosage Cytokines - physiology Cytotoxicity, Immunologic - immunology Drug Synergism Epitopes, T-Lymphocyte - immunology Female Granulocyte-Macrophage Colony-Stimulating Factor - administration & dosage HIV-1 - immunology Human immunodeficiency virus Immunity, Innate Interleukin-12 - administration & dosage Intestinal Mucosa - immunology Intestinal Mucosa - metabolism Intestinal Mucosa - virology Lymphocyte Activation - immunology Mice Mice, Inbred BALB C Molecular Sequence Data Peyer's Patches - cytology Peyer's Patches - immunology Peyer's Patches - virology Spleen - cytology Spleen - immunology Spleen - virology T-Lymphocytes, Cytotoxic - immunology T-Lymphocytes, Cytotoxic - virology Vaccines, Synthetic - administration & dosage Vaccines, Synthetic - immunology |
Title | Interplay of Cytokines and Adjuvants in the Regulation of Mucosal and Systemic HIV-Specific CTL |
URI | http://www.jimmunol.org/cgi/content/abstract/165/11/6454 https://www.ncbi.nlm.nih.gov/pubmed/11086085 https://search.proquest.com/docview/17731628 |
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