Vectored immunoprophylaxis protects humanized mice from mucosal HIV transmission

Alejandro B Balazs, Yong Ouyang, Christin M Hong, Joyce Chen, Steven M Nguyen, Dinesh S Rao, Dong Sung An     & David Baltimore. Nat. Med., (2014) 20, 296-300.

Speaker: Wei-Han Deng (鄧暐翰)                                        Time: 15:00~16:00, May. 6, 2015

Commentator: Dr. Guey-Chuen Perng (彭貴春 老師)        Place: Room 601

Abstract

More than 60 million people worldwide have been infected with human immunodeficiency virus (HIV), and nearly half of these individuals have died. The development of a safe and effective HIV vaccine is a global health priority. Broadly neutralizing antibodies that target HIV have demonstrated the potential protection during the infection. However, it is unclear whether immunogens can be designed that will elicit these rare antibodies efficiently. Vectored immunoprophylaxis (VIP), the transfer of genes encoding antibodies, is a novel protective strategy that bypasses the natural immune response by directing the production of antibodies from nonhematopoietic tissues, such as muscle. Because this approach skips many of the steps in the usual path of vaccine development, it has been described as a 'leapfrog' strategy. In previous studies, the authors demonstrated that the ability of VIP to prevent intravenous transmission of the CXCR4-tropic NL4-3 HIV strain in humanized mice using VRC01 and b12 monoclonal antibodies. Therefore, they further challenged humanized mice with CCR5-tropic JR-CSF HIV strain. Results have shown that only VRC01 could prevent the loss of CD4⁺ T cells in humanized mice and provide the protection. Furthermore, they modified the established high-dose, single vaginal challenge model in BLT humanized mice to implement a repetitive, non-abrasive, low-dose viral challenge. This model can better reflect the stochastic nature of human transmission. Later on, the authors set out to determine the minimum protective dose of recently isolated antibodies to ascertain their in vivo potency. The data show that animals receiving VIP that expresses a modified VRC07 antibody were completely resistant to repetitive intravaginal challenge by a heterosexually transmitted founder HIV strain. In conclusion, VIP may be effective in preventing vaginal transmission of HIV between humans.

References

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