Deglycosylation of HIV-1 AE Gp140 enhances the capacity to elicit neutralizing antibodies against the heterologous HIV-1 clade.
The aim of this study was to test whether deglycosylation of an HIV-1 AE recombinant-derived gp140 could enhance the induction of neutralizing antibodies. N-to-Q mutations were introduced in the V1/V2 (m157/161) or V4 (m382/388) loops by using overlapping PCR. BALB/c mice were inoculated with different DNA vaccines at weeks 0, 2, 4, and 7. The Elispot assay was used to quantify Env-specific T-cell immunity, and the TZM-bl cell-based in vitro neutralizing assay with primary isolates was used to assess humoral immune responses. Our data showed that two mutant DNA vaccines, designated m157/161 and m382/388, mounted total T-cell responses that were at levels similar those of the unmutated vaccine. Although the levels of binding antibodies elicited by the two mutants were significantly lower than the levels elicited by the unmutated vaccine, cross-reactive neutralizing antibodies were observed only in the sera that received the mutant DNA vaccines. These data demonstrate that deglycosylation of HIV-1 Env could enhance the capacity to elicit cross-reactive neutralizing antibodies.
Zhang
Congyou
C
Shanghai Public Health Clinical Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Wan
Yanmin
Y
Shi
Jijing
J
Zhou
Mingzhe
M
Meng
Zhefeng
Z
Yuan
Songhua
S
Qiu
Chao
C
Zhang
Xiaoyan
X
Xu
Xuemei
X
Liu
Chaoqi
C
Xu
Jianqing
J
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D002460:Cell Line; D003429:Cross Reactions / Q000276:immunology; D006031:Glycosylation; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000145:classification / Q000276:immunology*; D006801:Humans; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D009154:Mutation; D009500:Neutralization Tests; D016133:Polymerase Chain Reaction / Q000379:methods; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1