Special Issue "Advances in Antibody-based HIV-1 Vaccine Development"
A special issue of Vaccines (ISSN 2076-393X).
Deadline for manuscript submissions: closed (30 June 2019) | Viewed by 58449
Despite the great success of antiretroviral therapy, both in the treatment and prevention of HIV-1 infection, a vaccine is still urgently needed to end the epidemic. Intensive collaborative work in the last decade resulted in the isolation of antibodies from a subset of HIV-positive patients, that can potently neutralize a broad spectrum of primary HIV-1 isolates in vitro and protect from infection in animal models, advancing these broadly neutralizing antibodies (bnAbs) to clinical trials in recent years. In parallel, detailed structural characterizations of bnAbs in complex with HIV-1 envelope proteins (Env) gave structural insights into particular features of these antibodies and their epitopes. Unfortunately, HIV-1 Env immunogens derived from this knowledge were not able to date to induce bnAbs upon vaccination of humans or non-human primates. However, they can do so in certain species like camelids or cows, which naturally generate antibodies with special characteristics of bnAbs. Detailed immunological studies are being performed to understand the generation of bnAbs in patients with the aim to recapitulate the underlying mechanisms in vaccination approaches. A continous coevolution of virus and antibodies driven by immunological escape mutants seems to be essential and serves as the basis for the generation of a series of Env immunogens for the next vaccine trials. Besides neutralization, Fc-mediated effector functions of antibodies are also important to control viremia by targeting cytotoxic immune activities to HIV-1 infected cells, thus potentially eliminating viral reservoirs in the body. In view of future therapeutic vaccine trials, the focus will be on choosing the right combinations of antibodies as well as delivery modes in order to achieve persisting and highly effective antibody concentrations. For prophylactic passive vaccine trials, bnAbs or derivatives may be particularly interesting to prevent infection in high risk cohorts. For classical active vaccination programs it has to be shown whether suitable Env immunogens can be identified that are able to stimulate naive B cell precursors in large populations to generate bnAbs.
Dr. Ursula Dietrich
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- HIV-1 vaccine development
- broadly neutralizing antibodies
- natural vs. vaccine-induced antibody response
- effector functions of antibodies
- structure-based immunogen design
- vectors for vaccine delivery
- perspectives for clinical applications