Induction of neutralizing antibody against human immunodeficiency virus type 1 (HIV-1) by immunization with gp41 membrane-proximal external region (MPER) fused with porcine endogenous retrovirus (PERV) p15E fragment.
The membrane-proximal external region (MPER) of HIV-1 gp41 is recognized by all three anti-HIV antibodies 2F5, 4E10 and Z13 that were directly derived from AIDS patients and have broader anti-HIV neutralizing activities. Thus, the MPER has been the focus of anti-HIV vaccine design and development. However, it has been unsuccessful to generate anti-HIV neutralizing antibodies targeting this region. One possible reason is that the MPER-containing immunogens have failed to maintain the correct conformation of the MPER present within the HIV-1 viral gp41 protein. The porcine endogenous retrovirus (PERV) p15E protein is structurally similar to HIV-1 gp41, and it was recently reported that the p15E fragment can be expressed in soluble form and was capable of inducing neutralizing antibodies against the epitope within the MPER of PERV p15E. In the present study, we attempted to use the p15E fragment as a carrier and fused the HIV-1 gp41 MPER with the p15E fragment. The vesicular stomatitis virus (VSV) recombinants expressing the fusion proteins (HIV-1 gp41 MPER-p15E) were prepared as primary immunogens, and the soluble fusion protein purified from a baculovirus expression system as booster immunogens. Our results showed that the antisera obtained from immunized rabbits specifically recognized the MPER determinant presented in the gp41 fragment. Importantly, we found that the antisera had neutralizing activities against HIV-1 viruses containing HIV-1 HXB2 and JRFL envelope glycoproteins. These results offer a new strategy for HIV-1 vaccine design and development targeting the gp41 MPER.
Luo
Min
M
Department of Cell Biology and Genetics, The College of Life Sciences, No. 5 Yi He Yuan Road, Peking University, Beijing 100871, China.
Yuan
Fei
F
Liu
Yanxia
Y
Jiang
Siming
S
Song
Xijun
X
Jiang
Pengfei
P
Yin
Xiaolei
X
Ding
Mingxiao
M
Deng
Hongkui
H
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D018929:Cell Culture Techniques; D017988:Gammaretrovirus / Q000235:genetics / Q000276:immunology; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007114:Immunization; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018411:Spodoptera
D016915:AIDS Vaccines; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D011994:Recombinant Proteins