title: Altering the Specificity of the Antibody Response to HIV gp120 with a Glycoconjugate Antigen.
abstract: Some conserved glycans on the HIV envelope protein are targets of broadly neutralizing antibodies (bnAbs) of HIV. BnAbs provide a precise definition of broadly neutralizing epitopes on the envelope protein of HIV. These epitopes are promising for vaccine design. Many glycan-related antigens with high affinity to bnAbs have been tested as immunogens in vivo. However, it was found that no bnAb-like antibodies were induced. Vaccination with different immunogens containing the same neutralizing epitope may enhance the affinity maturation of antibodies which focus on the shared epitope. This combined immunization strategy showed great potential in peptide epitope-based vaccine design. However, it has not yet been explored on glycan-related epitopes to date. Herein, we take 2G12 as a model to validate this strategy on glycan-related epitopes. A high-affinity antigen of 2G12 was constructed by conjugating the D1 arm tetramannoside to bovine serum albumin. Then, the glycoconjugate was coimmunized with a recombinant gp120, which was expected to selectively benefit the induction of antibodies recognizing the neutralizing epitope of 2G12 on gp120. Mice were inoculated with the two antigens simultaneously or alternately to determine the suitable regimen for this strategy. The serological assays demonstrated that the antibody titers and subtypes responded to the whole gp120 were not improved, and the proportion of antibodies competitively bound to the 2G12 epitope was not enhanced significantly either. However, the coimmunized glycoconjugate selectively raised the proportion of antibodies recognizing D1 arm tetramannoside-related structures on gp120. These results provide important experience for the design of glycan-dependent bnAb-based vaccines.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University , Xue Yuan Rd No. 38, Beijing 100191, China.
authors.forename: Chang-Cheng
authors.initials: CC
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University , Xue Yuan Rd No. 38, Beijing 100191, China.
authors.forename: Canjia
authors.initials: C
authors.lastname: Zhai
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University , Xue Yuan Rd No. 38, Beijing 100191, China.
authors.forename: Xiu-Jing
authors.initials: XJ
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University , Xue Yuan Rd No. 38, Beijing 100191, China.
authors.forename: Xin-Shan
authors.initials: XS
authors.lastname: Ye
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology; D000917:Antibody Formation; D000941:Antigens / Q000737:chemistry / Q000276:immunology*; D000080908:Broadly Neutralizing Antibodies; D002417:Cattle; D000939:Epitopes; D005260:Female; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000276:immunology*; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D008351:Mannans / Q000138:chemical synthesis / Q000276:immunology*; D008807:Mice, Inbred BALB C; D009844:Oligosaccharides / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: C529157:2G12 monoclonal antibody; D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000941:Antigens; D000080908:Broadly Neutralizing Antibodies; D000939:Epitopes; D006001:Glycoconjugates; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D008351:Mannans; D009844:Oligosaccharides; D014614:Vaccines, Synthetic; C028569:oligomannoside; D012710:Serum Albumin, Bovine