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Development of cell-expressed and virion-incorporated CCR5-targeted vaccine
Authors:Misumi Shogo  Eto Ayumi  Mitsumata Ryotarou  Yamada Masanori  Takamune Nobutoki  Shoji Shozo
Institution:a Department of Pharmaceutical Biochemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Kumamoto 862-0973, Japan
b Kumamoto Health Science University, Kumamoto 861-5598, Japan
Abstract:Our previous study demonstrated that the immunization with a cycloimmunogen derived from extracellular loop-2 (ECL-2) of CCR5 (cDDR5) attenuated acute phase of CCR5-tropic simian-human immunodeficiency virus (SHIV)SF162P3 replication in vivo. Although the study showed that the antisera raised against cDDR5 reacted with cell-expressed CCR5, we have not yet demonstrated whether the antisera can react with virion-incorporated CCR5. Here, we show that rhesus cDDR5 (rcDDR5)-specific antibodies react with not only cell-expressed but also virion-incorporated simian CCR5s (siCCR5s), but may predominantly exert their inhibitory effects on simian immunodeficiency virus (SIV) infection by the binding of cell-expressed rather than virion-incorporated CCR5s. These results suggest that the virion-incorporated CCR5 may contribute to the reactivation of the anti-rcDDR5 antibody-producing B-cells by SIV particles after rcDDR5 immunization, although the binding of anti-rcDDR5 antibody to virion-incorporated CCR5 results in a partial inhibitory effect on SIV infection.
Keywords:SHIV  simian-human immunodeficiency virus  ECL-2  extracellular loop-2  siCCR5  simian CCR5  SIV  simian immunodeficiency virus  UPA  undecapeptidyl arch  HIV  human immunodeficiency virus  R5  CCR5-tropic
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