A critical question for HIV vaccine development Which antibo(2)

A critical question for HIV vaccine development Which antibodies to induce.

PERSPECTIVE

elicit a protective immune response medi-ated primarily by antibodies (Abs).This is particularly challenging in the case of HIV because the virus mutates rapidly,leading to many viral subgroups.A successful vaccine would therefore need to elicit Abs that are able to recognize a range of genetically diverse strains.

response in nearly all infected individuals,only ~1%produce Abs that can neutralize a wide range of HIV subtype Abs (1),and only ~10to 25%of HIV-infected subjects produce cross-neutralizing Ab responses with moderate breadth and po-tency.The majority of infected individuals make “conventional Abs ”that have limited breadth and potency in standard neutralization assays characteristics of conventional and bnAbs is shown in Table 1.A great deal of effort and funding cur-rently supports the design of vaccine regimens that will elicit these exceptional bnAbs,because it is thought that such a vaccine would induce high levels of protection.However,extensive data suggest that vaccine-induced conventional Abs may provide a level of protection that could have a considerable impact on the epidemic.Many factors contribute to the rarity of bnAbs in patients and the difficulty of inducing them by vaccination:(i)the epitopes they target are poorly immunogenic;(ii)bnAbs are character-ized by extensive somatic hypermutation (4,5);(iii)bnAbs are often polyreactive and/or autor-eactive (6,7);(iv)bnAbs display unusual structural characteristics in their antigen binding region (8–10);and (v)bnAbs take months to years to evolve in response to virus evolution within the host (11–13).Since their discovery,a critical ques-tion for HIV vaccine development has been whether to design vaccines that stimulate these exceptional bnAbs.This approach would repre-sent a departure from previous vaccine strategies that elicit conventional Abs —i.e.,Abs that are normally induced by infection or vaccines that are not highly mutated from germline immuno-globulin genes and do not display unusual struc-tural or genetic characteristics (14,15).Therefore,the induction of exceptional bnAbs through vac-cination is a new and major challenge.Although this approach has not been attempted previously,there is a general consensus that a set of immu-nogens will be needed to “guide ”the immune SCIENCE 11JULY 2014•VOL 345ISSUE 6193

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New York Veterans Affairs Harbor Healthcare System,New E-mail:zollas01@med.nyu.edu