[PDF][PDF] Broadly neutralizing antibodies for HIV-1 prevention or immunotherapy

M Caskey, F Klein, MC Nussenzweig - N Engl J Med, 2016 - natap.org
M Caskey, F Klein, MC Nussenzweig
N Engl J Med, 2016natap.org
Despite tremendous efforts to prevent transmission of human immunodeficiency virus type 1
(HIV-1), new infections and AIDS-related deaths continue to be a global problem.
Antiretroviral therapy (ART) can effectively suppress HIV-1 replication and limit disease
progression. However, ART fails to eradicate the virus, and suppression requires lifelong
therapy, which may have side effects and poses a risk of the development of resistance.
New approaches to preventing and treating HIV-1 infection are therefore necessary to …
Despite tremendous efforts to prevent transmission of human immunodeficiency virus type 1 (HIV-1), new infections and AIDS-related deaths continue to be a global problem. Antiretroviral therapy (ART) can effectively suppress HIV-1 replication and limit disease progression. However, ART fails to eradicate the virus, and suppression requires lifelong therapy, which may have side effects and poses a risk of the development of resistance. New approaches to preventing and treating HIV-1 infection are therefore necessary to contain the epidemic and to bolster nascent efforts to find a cure. A new generation of highly potent broadly neutralizing antibodies (bNAbs) may represent a promising approach to combating HIV-1 infection. 1 Although antibodies that neutralize HIV-1 were discovered shortly after the disease was first described, most HIV-1–infected people produce nonneutralizing antibodies or antibodies that neutralize only a limited number of different HIV-1 strains. However, high serum titers of HIV-1 neutralizing activity develop in a small fraction of infected persons. In contrast to the typical antibody response, bNAbs can take years to develop, and it has not yet proved possible to elicit them by standard immunization strategies. Isolation of bNAbs from infected persons with high levels of HIV-1–neutralizing serum activity (so-called elite neutralizers) was not easily achieved until the advent of single-cell–based anti-HIV-1 antibody cloning techniques. 2 The anti–HIV-1 antibodies obtained
natap.org