Scientific challenge and advances of the HIV vaccine research

Abstract

After experiencing the failures of first and second generations of HIV vaccines, the RV144 trial in Thailand, combining pox virus and gp120 vaccines, shows a 31% protection for the first time in human study. The main scientific challenge to the vaccine of a Lentivirus where HIV belongs, is the lack of protective immunity in natural infection. Therefore, novel approaches have to be developed to overcome this bottleneck in evolution. Research progresses are made in the following areas: Finding the extremely broad neutralizing antibody (bNAb) and studying their maturation mechanism from the elite controller in HIV infected people; rational design of novel HIV immunogen to trigger germline B cells activation of the bNAb; stabilizing the HIV envelope trimers and enhancing their ability to induce bNAb; using replication competent vector to strengthen the immunogenicity and durability. Only four phase IIb/III clinical trials have been conducted in the first 30 years of HIV vaccine research. More than five phase IIb/III HIV vaccine clinical trials have been planned for the next 5 years. To repeat the RV144 trial in African, NIH started the P5 project of ALVAC/gp120 vaccine started in late 2016. The Harvard and Johnson’s collaborative Ad 26/GP140 vaccine trial will be initiated in 2017/2018. To compare the replicating (rTV) and non-replication (ALVAC) pox virus vector, China CDC and NIH will conduct a joint trial of combining their DNA/rTV with gP145 vaccines in China. The two funded CHAVI-ID groups led by Duke University and the Scripps Research Institute as well as the Vaccine Research Center of NIH will push their HIV env trimer vaccine to Phase IIb trials. With the past successes in the first two lentivirus (EIAV and FIV) vaccines and the 31% human protection of RV144, HIV vaccine research will definitely contribute to the course of Ending AIDS Epidemic by 2030.