Priming a broadly neutralizing antibody response to HIV-1 using a germline-targeting immunogen
2015; American Association for the Advancement of Science; Volume: 349; Issue: 6244 Linguagem: Inglês
10.1126/science.aac5894
ISSN1095-9203
AutoresJoseph G. Jardine, Takayuki Ota, Devin Sok, Matthias Pauthner, Daniel W. Kulp, Oleksandr Kalyuzhniy, Patrick Skog, Theresa C. Thinnes, Deepika Bhullar, Bryan Briney, Sergey Menis, Meaghan Jones, Mike Kubitz, Skye Spencer, Yumiko Adachi, Dennis R. Burton, William R. Schief, David Nemazee,
Tópico(s)Herpesvirus Infections and Treatments
ResumoSteps in the right direction HIV-1 mutates rapidly, making it difficult to design a vaccine that will protect people against all of the virus' iterations. A potential successful vaccine design might protect by eliciting broadly neutralizing antibodies (bNAbs), which target specific regions on HIV-1's trimeric envelope glycoprotein (Env) (see the Perspective by Mascola). Jardine et al. used mice engineered to express germline-reverted heavy chains of a particular bNAb and immunized them with an Env-based immunogen designed to bind to precursors of that bNAb. Sanders et al. compared rabbits and monkeys immunized with Env trimers that adopt a nativelike conformation. In both cases, immunized animals produced antibodies that shared similarities with bNAbs. Boosting these animals with other immunogens may drive these antibodies to further mutate into the longsought bNAbs. Chen et al. report that retaining the cytoplasmic domain of Env proteins may be important to attract bNAbs. Removing the cytoplasmic domain may distract the immune response and instead generate antibodies that target epitopes on Env that would not lead to protection. Science , this issue p. 139 , 10.1126/science.aac4223 , p. 156 ; see also p. 191
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