![Figure 1. HIV-1 infection in humanized mice passively infused with b12-IgA or b12-IgG isotype. (A) Neutralization activity of anti-HIV human mAb b12-IgA. Reporter cell line TZM-bl cells that express CD4, CXCR4, CCR5, and a Tat-responsive reporter gene for luciferase were infected with 200 TCID50 of replication-defective pseudovirus containing Env (SF162.LS) in the presence of various concentrations of anti-HIV monoclonal antibodies. Neutralization activity was measured by the reduction in luciferase reporter gene expression after a single round of pseudovirus infection in TZM-bl cells in triplicate. b12-IgG1 and the recombinant b12-IgA2 were compared at indicated concentrations. (B) Antibody level in circulation after passive transfer. NSG-hu mice were injected intravenously with various concentrations of purified b12-IgA2 (pIgA: mIgA = 1:1, mass ratio) or b12-IgG1 and the blood was collected after 4 hours. The plasma antibody concentrations were measured using ELISA. (n = 4-6, mean ± SEM). (C-D) Concentrations of b12 antibodies in plasma (C) or genital secretions (D) at the time of challenge. NSG-hu mice were injected intravenously with either 200 μg of b12-IgA2 or 20 μg of b12-IgG1 per mouse. Blood and genital secretions were collected after 4 hours. (E-I) Peripheral CD4+ T cell loss after HIV-1 challenge in NSG-hu mice injected with different b12 antibody isotypes; (E) purified human IgG/κ control antibody (hIgG/κ); (F) b12-IgA2 includes both monomeric and polymeric IgA as described in (B), (b12IgA2 [M+P]); (G) b12-IgG1; (H) b12-IgA2 monomer only (b12IgA2 [M]). Mice were challenged intravaginally with HIV-1JR-CSF. (I) Average percent CD4+ T cells in CD3 T cells in PBMCs at each time points (n = 5-9). Statistical analysis was performed using unpaired t test. (*P = .0313 and ***P < .0001 between IgA [M+P] +HIV and control Ab [hIgG/κ] + HIV). (J) Plasma viral loads in HIV infected NSG-hu mice. HIV viral RNA was measured by Abbott HIV viral load test. Dotted line indicates the detection limit. (N/D indicates not detected; n = 4, indicated P values are from unpaired t test between Ab-treated groups with HIV and hIgG/κ-treated groups with HIV.)](https://ash.silverchair-cdn.com/ash/content_public/journal/blood/120/23/10.1182_blood-2012-04-422303/4/zh89991299780001.jpeg?Expires=1736050539&Signature=E5W85nJO4rH6gwP8JFEvJrP0~e0HX2kBcdHMwffNByakKu0~CeT-YxBLiRqwNU7eo9cjqSQZJGiRGcxoft11IwFA9vH9viCSwuJqpPkBTS3i8Aw4ylZmgvtGOBtlY9WFgOdvPqtg5eVkeDt-NrmHL3oXCV1gFICMdV~1dlJEaa0ymoIxORsKxSVkGjmTndjet1ZeAcqxp3XfnY8ppi0NIFfzxH1WCJXZQp5EDWHSLDphynwWPELzxN6UDfTZVSjfXe5vS6mF6Ecce2sxVEH5dgANZqo~VhtB4JB8z0wznBGpV2kjB4LgW0HG5jMzPGM40MtEknXNC0hDxO5pNMFhHA__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
HIV-1 infection in humanized mice passively infused with b12-IgA or b12-IgG isotype. (A) Neutralization activity of anti-HIV human mAb b12-IgA. Reporter cell line TZM-bl cells that express CD4, CXCR4, CCR5, and a Tat-responsive reporter gene for luciferase were infected with 200 TCID50 of replication-defective pseudovirus containing Env (SF162.LS) in the presence of various concentrations of anti-HIV monoclonal antibodies. Neutralization activity was measured by the reduction in luciferase reporter gene expression after a single round of pseudovirus infection in TZM-bl cells in triplicate. b12-IgG1 and the recombinant b12-IgA2 were compared at indicated concentrations. (B) Antibody level in circulation after passive transfer. NSG-hu mice were injected intravenously with various concentrations of purified b12-IgA2 (pIgA: mIgA = 1:1, mass ratio) or b12-IgG1 and the blood was collected after 4 hours. The plasma antibody concentrations were measured using ELISA. (n = 4-6, mean ± SEM). (C-D) Concentrations of b12 antibodies in plasma (C) or genital secretions (D) at the time of challenge. NSG-hu mice were injected intravenously with either 200 μg of b12-IgA2 or 20 μg of b12-IgG1 per mouse. Blood and genital secretions were collected after 4 hours. (E-I) Peripheral CD4+ T cell loss after HIV-1 challenge in NSG-hu mice injected with different b12 antibody isotypes; (E) purified human IgG/κ control antibody (hIgG/κ); (F) b12-IgA2 includes both monomeric and polymeric IgA as described in (B), (b12IgA2 [M+P]); (G) b12-IgG1; (H) b12-IgA2 monomer only (b12IgA2 [M]). Mice were challenged intravaginally with HIV-1JR-CSF. (I) Average percent CD4+ T cells in CD3 T cells in PBMCs at each time points (n = 5-9). Statistical analysis was performed using unpaired t test. (*P = .0313 and ***P < .0001 between IgA [M+P] +HIV and control Ab [hIgG/κ] + HIV). (J) Plasma viral loads in HIV infected NSG-hu mice. HIV viral RNA was measured by Abbott HIV viral load test. Dotted line indicates the detection limit. (N/D indicates not detected; n = 4, indicated P values are from unpaired t test between Ab-treated groups with HIV and hIgG/κ-treated groups with HIV.)
