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    GlaxoSmithKline attachment inhibitor fostemsavir III demonstrates strong clinical efficacy
    Date:Jul 26, 2019

          Cytomegalovirus (CMV) based vaccine vectors have strong T cell induction and resistance to a variety of pathogens. However, CMV is harmful to people with immunodeficiency or immunosuppression.


          Previous studies have confirmed that rhesus monkey cytomegalovirus (RhCMV) strain 68-1 derived virus vector expressing simian immunodeficiency virus (SIV) protein (68-1 RhCMV/SIV) can initiate and maintain cellular immune response, thereby protecting rhesus monkeys from mucosal attack by highly pathogenic SIV. However, these effective 68-1 RhCMV/SIV vectors have the ability to replicate and transmit, so they have the potential to cause disease in immunocompromised subjects.


          To develop a safer CMV-based clinical vaccine, researchers from Oregon University of Health and Sciences, Frederick National Cancer Research Laboratory and Fred Hutchinson Cancer Research Center in the United States attenuated the R110 gene (Rh110), which encodes the membrane protein pp71, in a new study. The virulence of 68-1 RhCMV/SIV vectors allows the suppression of cleavage gene expression. Relevant research results were published in the July 17, 2019 Journal Science Translational Medicine, entitled "A live-attenuated RhCMV/SIV vaccine shows long-term efficacy against heterologous SIV challenge".


          Compared with 68-1 RhCMV/SIV viral vectors whose virulence was not weakened, Rh11068-1 RhCMV/SIV viral vectors had a high transmission defect in vivo (that is, they could not transmit efficiently in vivo). Their transmission ability decreased by about 1000 times, but they could still infect RhCMV-positive rhesus monkeys repeatedly, and they had a high real estate rate. Effective effect - memory biased T cell response.


          These researchers confirmed that the Rh11068-1 RhCMV/SIV vectors expressing homologous or heterologous SIV antigens were highly effective against intravaginal SIVmac239 virus (a highly pathogenic strain of SIV, a non-human primate retrovirus similar to HIV): 59% of the vaccines received (i.e., Rh11068). - In rhesus monkeys inoculated with 1 RhCMV/SIV vector, it controls SIV infection and progressively clears SIV. In addition, nine of the 12 rhesus monkeys who received the vaccine controlled the initial SIV attack and gradually cleared the SIV were able to strictly control the second SIV attack about three years after the last vaccination, which confirmed the sustainability of the vaccine.



          Therefore, the Rh11068-1 RhCMV/SIV vector is safe and effective, which will be helpful for clinical evaluation of the corresponding human cytomegalovirus (HCMV) vector as a preventive HIV/AIDS vaccine in the future. The mutation of HCMV should be able to produce a powerful but restricted HCMV virus vector, which may be widely used in human body.


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