title: Comparative mucosal immunogenicity of HIV gp41 membrane-proximal external region (MPER) containing single and multiple repeats of ELDKWA sequence with defensin peptides.
abstract: The MPER of gp41 of HIV-1 has received great attention and is widely recognized as a promising target for the development of AIDS vaccine. We investigated the ability of trirepeat of ELDKWA sequence of gp41 antigen with defensins in liposome using multiple-shot immunization strategy in the mice model. The designed was used to enhance the immunogenicity and exposure of MPER in its native conformation for the induction of MPER-specific HIV-1 neutralizing antibodies. To characterize, we estimated the antibody levels (IgG/IgA) in serum as well as in lung, intestinal, vaginal and rectal washes till day 120 in outbred and inbred (H-2(b) and H-2(d)) mice using liposome as delivery vehicle. The representative sera and washes were also tested for in vitro neutralization with CCR5-tropic Indian HIV-1 primary isolates. We observed that the modified HIV antigen containing trirepeat of ELDKWA with defensins was showing significantly (p<0.001) higher IgG/IgA antibody titre (102,400-204,800) in sera as well as in different mucosal washes (1600-6400) than standard HIV-1 antigen. Furthermore, sera from the modified HIV-1 antigen with defensins found to exhibit higher neutralizing activities (ranging from 59.3% to 84.6%) than the standard HIV-1 antigen. These results show that the induction of MPER-specific HIV-1 neutralizing antibodies could be achieved through a rationally designed vaccine strategy.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences (A.I.I.M.S.), Ansari Nagar, New Delhi 110029, India. Electronic address: mohan.teena@gmail.com.
authors.forename: Teena
authors.initials: T
authors.lastname: Mohan
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences (A.I.I.M.S.), Ansari Nagar, New Delhi 110029, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Verma
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences (A.I.I.M.S.), Ansari Nagar, New Delhi 110029, India. Electronic address: dnrao311@hotmail.com.
authors.forename: D N
authors.initials: DN
authors.lastname: Rao
mesh_terms: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D020816:Amino Acid Motifs / Q000276:immunology*; D000818:Animals; D019138:Antibodies, Blocking / Q000378:metabolism; D000914:Antibodies, Viral / Q000378:metabolism; D023082:Defensins / Q000276:immunology*; D004195:Disease Models, Animal; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects; D007114:Immunization; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D019138:Antibodies, Blocking; D000914:Antibodies, Viral; D023082:Defensins; D018985:Epitopes, B-Lymphocyte; D015700:HIV Envelope Protein gp41; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008081:Liposomes; D010455:Peptides; C514787:gp41 protein, Human immunodeficiency virus 1
keywords: Defensins; HIV; IgG/IgA antibodies; MPER; Neutralization; gp41