OBJECTIVE: To elicit broadly neutralizing antibody activity by combining polyclonal human serum IgG antibodies with HIVgp120, human leukocyte antigen (HLA) class I or class II and 70 kDa heat shock protein. DESIGN: : In addition to HIV antigens, HIV-1 virions express HLA class I, HLA class II and 70 kDa heat shock protein molecules, which have quantitative and functional significance. The complementary effect of combining human polyclonal IgG antibodies with these antigens may result in effective broad spectrum neutralizing activity. METHODS: Polyclonal human sera with IgG antibodies and monoclonal antibody to HLA class I or class II, HIVgp120 and 70 kDa heat shock protein were selected and used in single, double or triple combinations. Dose-dependent inhibition studies of HIV-1 clades A, B, C and D were carried out using human CD4 T cells treated with the combinations of human sera and with monoclonal antibodies for clade B. The results are presented as half maximal (IC50) inhibitory concentration and maximum inhibition by these sera. RESULTS: The half maximal (IC50) inhibitory concentration of clade B HIV-1 infection with single or a combination of two antisera was higher than those with three antisera, which also showed maximum inhibition of HIV-1. Further investigations of human sera with HIV-1 clades C and D also showed lower half maximal (IC50) inhibitory concentrations and higher maximum inhibition with combinations of the three antisera, but this was not seen with clade A. CONCLUSION: A novel vaccination strategy eliciting broadly neutralizing antibody activity to the CCR5-using HIV-1 clades B, C and D has been demonstrated by the trimolecular complex of human antisera with HLA class II or class I, HIVgp120 and 70 kDa heat shock protein.
OBJECTIVE: To elicit broadly neutralizing antibody activity by combining polyclonal human serum IgG antibodies with HIVgp120, human leukocyte antigen (HLA) class I or class II and 70 kDa heat shock protein. DESIGN: : In addition to HIV antigens, HIV-1 virions express HLA class I, HLA class II and 70 kDa heat shock protein molecules, which have quantitative and functional significance. The complementary effect of combining human polyclonal IgG antibodies with these antigens may result in effective broad spectrum neutralizing activity. METHODS: Polyclonal human sera with IgG antibodies and monoclonal antibody to HLA class I or class II, HIVgp120 and 70 kDa heat shock protein were selected and used in single, double or triple combinations. Dose-dependent inhibition studies of HIV-1 clades A, B, C and D were carried out using human CD4 T cells treated with the combinations of human sera and with monoclonal antibodies for clade B. The results are presented as half maximal (IC50) inhibitory concentration and maximum inhibition by these sera. RESULTS: The half maximal (IC50) inhibitory concentration of clade B HIV-1 infection with single or a combination of two antisera was higher than those with three antisera, which also showed maximum inhibition of HIV-1. Further investigations of human sera with HIV-1 clades C and D also showed lower half maximal (IC50) inhibitory concentrations and higher maximum inhibition with combinations of the three antisera, but this was not seen with clade A. CONCLUSION: A novel vaccination strategy eliciting broadly neutralizing antibody activity to the CCR5-using HIV-1 clades B, C and D has been demonstrated by the trimolecular complex of human antisera with HLA class II or class I, HIVgp120 and 70 kDa heat shock protein.
Authors: Lesley A Bergmeier; Kaboutar Babaahmady; Jeffrey Pido-Lopez; Kate J Heesom; Charles G Kelly; Thomas Lehner Journal: Immunology Date: 2009-11-25 Impact factor: 7.397