Broader HIV-1 neutralizing antibody responses induced by envelope glycoprotein mutants based on the EIAV attenuated vaccine

Lianxing Liu,Haishan Li,Liying Ma,Huiguang Li,Yanmin Wan,Jianping Sun,Yiming Shao,Lan Wu

doi:10.1186/1742-4690-7-71

Abstract

BackgroundIn order to induce a potent and cross-reactive neutralizing antibody (nAb), an effective envelope immunogen is crucial for many viral vaccines, including the vaccine for the human immunodeficiency virus (HIV). The Chinese equine infectious anemia virus (EIAV) attenuated vaccine has controlled the epidemic of this virus after its vaccination in over 70 million equine animals during the last 3 decades in China. Data from our past studies demonstrate that the Env protein of this vaccine plays a pivotal role in protecting horses from both homologous and heterogeneous EIAV challenges. Therefore, the amino acid sequence information from the Chinese EIAV attenuated vaccine, in comparison with the parental wild-type EIAV strains, was applied to modify the corresponding region of the envelope glycoprotein of HIV-1 CN54. The direction of the mutations was made towards the amino acids conserved in the two EIAV vaccine strains, distinguishing them from the two wild-type strains. The purpose of the modification was to enhance the immunogenicity of the HIV Env.ResultsThe induced nAb by the modified HIV Env neutralized HIV-1 B and B'/C viruses at the highest titer of 1:270. Further studies showed that a single amino acid change in the C1 region accounts for the substantial enhancement in induction of anti-HIV-1 neutralizing antibodies.ConclusionsThis study shows that an HIV envelope modified by the information of another lentivirus vaccine induces effective broadly neutralizing antibodies. A single amino acid mutation was found to increase the immunogenicity of the HIV Env.

Highlights

In order to induce a potent and cross-reactive neutralizing antibody, an effective envelope immunogen is crucial for many viral vaccines, including the vaccine for the human immunodeficiency virus (HIV)
Vaccines Construction From the sequence analysis of two Chinese vaccinederived wild-type equine infectious anemia virus (EIAV) strains (LN40 and D510) and two vaccine virus strains (DLV and FDDV), 10 consensus amino acid mutations were identified in the EIAV Env region [2] (Figure 1a)
We modified the HIV-1 gp145 DNA vaccine and recombinant vaccinia vaccine by introducing all of the EIAV amino acid mutations (Table 1 and Figure 1b). They were based on the structural information of the attenuated EIAV vaccine [5,6] (Figure 1c)

Summary

Introduction

In order to induce a potent and cross-reactive neutralizing antibody (nAb), an effective envelope immunogen is crucial for many viral vaccines, including the vaccine for the human immunodeficiency virus (HIV). The clinical manifestations of infections by EIAV and HIV are different, the underlying mechanisms of persistence and pathogenesis are very similar [3,4]. Studies on the animal models of EIAV, FIV, and SIV showed that attenuated vaccines can be highly effective against infection by wild-type strains [18,19,20,21,22]. The Chinese EIAV donkey-leukocyte attenuated vaccine (DLV) was developed through long-term tissue culture attenuation (123 passages) from a highly pathogenic EIAV strain D510. The latter was obtained from in vivo passages (17 and 117 passages in horses and donkeys respectively) of a field EIAV isolates, LN40 strain.

Methods

Results

Conclusion