Effects of Immunization with CCR5-Based Cycloimmunogen on Simian/HIVSF162P3 Challenge
| Autor: | Takaaki Iiboshi, Kuniomi Tachibana, Masashi Kusaba, Nobutoki Takamune, Shibata Hideaki, Shozo Shoji, Mamoru Umeda, Shogo Misumi, Tadashi Nakasone, Masafumi Endo, Daisuke Nakayama, Ryouzaburo Mukai |
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| Rok vydání: | 2006 |
| Předmět: |
Receptors
CCR5 HIV Antigens Immunology Peptide Biology Simian Peptides Cyclic Macaque chemistry.chemical_compound biology.animal Extracellular Animals Humans Immunology and Allergy Autoantibodies AIDS Vaccines Antiserum chemistry.chemical_classification Vaccines Synthetic Dipeptide virus diseases Viral Load biology.organism_classification Virology In vitro Protein Structure Tertiary Macaca fascicularis Immunization chemistry HIV-1 Simian Immunodeficiency Virus |
| Zdroj: | The Journal of Immunology. 176:463-471 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.176.1.463 |
| Popis: | A synthetic cycloimmunogen targeting the HIV-1 coreceptor CCR5 was evaluated for its capacity to induce CCR5-specific Abs with anti-HIV-1 activity in cynomolgus macaques. The cyclic closed-chain dodecapeptide (cDDR5) mimicking the conformation-specific domain of human CCR5 was chemically prepared, in which the Gly-Glu dipeptide links the amino and carboxy termini of the decapeptidyl linear chain (Arg168 to Thr177) derived from the undecapeptidyl arch (Arg168 to Cys178) of extracellular loop-2 in CCR5. The immunization of cynomolgus macaques with the cDDR5-conjugated multiple-Ag peptide (cDDR5-MAP) induced anti-cDDR5 serum production for ∼15 wk after the third immunization. The antisera raised against cDDR5-MAP reacted with both human and macaque CCR5s, and potently suppressed infection by the R5 HIV-1 laboratory isolate (HIVJRFL), R5 HIV-1 primary isolates (clade A:HIV93RW004 and clade C:HIVMJ4), and a pathogenic simian/HIV (SHIVSF162P3) bulk isolate in vitro. To examine the prophylactic efficacy of anti-CCR5 serum Ab for acute HIV-1 infection, cynomolgus macaques were challenged with SHIVSF162P3. The cDDR5-MAP immunization attenuated the acute phase of SHIVSF162P3 replication. The geometric mean plasma viral load in the vaccinated macaques was 217.10 times lower than that of the control macaques at 1 wk postchallenge. Taken together, these results suggest that cDDR5-MAP immunization is an effective prophylactic vaccine strategy that suppresses and delays viral propagation during the initial HIV-1 transmission for the containment of HIV-1 replication subsequent to infection. |
| Databáze: | OpenAIRE |
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