Broadly Neutralizing Antibodies and the Promise of Universal Vaccines

Where Are We Now?

Kathleen L Hefferon

Disclosures

Immunotherapy. 2014;6(1):51-57. 

In This Article

Abstract and Introduction

Abstract

Recent research has provided strong support for the utility of broadly neutralizing antibodies generated against viruses, which inherently possess a high degree of antigenic variability (such as influenza virus or HIV) as a feasible means to prevent infection. Many of these antibodies share the ability to bind to highly conserved regions within the stem of the virus 'spike' or surface glycoprotein, in such a way that they interfere with virus entry, including membrane fusion. As a result, broadly neutralizing antibodies could be supplied to patients as a form of passive immunotherapy, as well as play a role in the design of new 'universal' vaccines and antiviral agents. The following article describes the most recent innovations in this exciting field.

Introduction

The ability to effectively prevent infection by viruses that possess high levels of antigenic variability, such as influenza virus and HIV-1, has proven to be a difficult task. In the vast majority of cases, this variability can be centered around the viral spike protein, which plays a role in both host cell-specific receptor binding and in enabling the virus to enter the host cell via receptor-mediated endocytosis. This spike glycoprotein actually consists of two domains, a receptor binding 'head' domain that contains the antigenic variability, and a 'stalk' or 'stem' domain that contains a fusogenic region. To date, much of the considerable challenge involved in using neutralizing antibodies or antiviral agents to block virus infection can be attributed to the rapid changes in the immunogenic head of the viral glycoproteins, hemagglutinin of influenza and Env of HIV-1. More recently, researchers have turned to the identification and utilization of broadly neutralizing antibodies, which are capable of successfully blocking infection of a wide spectrum of virus subtypes. Not only can broadly neutralizing antibodies be administered to patients as a form of passive immunotherapy, but information gathered from the nature of their interaction with highly conserved regions of the virus glycoprotein can strengthen the knowledge base necessary for the rational design of universal vaccines and antiviral molecules. This article discusses the potential of broadly neutralizing antibodies for immunotherapy against influenza, HIV-1 and other virus infections.

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