Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 May;9(3):250-6.
doi: 10.1097/COH.0000000000000056.

Adeno-associated virus delivery of broadly neutralizing antibodies

Affiliations
Review

Adeno-associated virus delivery of broadly neutralizing antibodies

Bruce C Schnepp et al. Curr Opin HIV AIDS. 2014 May.

Abstract

Purpose of review: In the present review, we will discuss the emerging field of vector-mediated antibody gene transfer as an alternative HIV vaccine. This approach is an improvement over classical passive immunization strategies that administer antibodies to the host to provide protection from infection. With vector-mediated gene transfer, the antibody gene is delivered to the host, resulting in long-term endogenous antibody expression from the injected muscle that confers protective immunity.

Recent findings: Large numbers of very potent and broadly neutralizing HIV antibodies have recently been isolated and characterized. Vector-mediated antibody gene transfer allows one to immediately use these antibodies as a vaccine. Gene transfer studies in both mice and monkeys demonstrate long-term antibody expression in serum from a single injection at concentrations that provide sterilizing immunity.

Summary: Vector-mediated antibody gene transfer can rapidly move existing, potent anti-HIV molecules into the clinic. The gene transfer products demonstrate a potency and breadth identical to the original product. This strategy eliminates the need for immunogen design and interaction with the adaptive immune system to generate protection, a strategy that so far has shown little promise.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Immunoprophylaxis by antibody gene transfer
Passive immunization involves intravenous delivery of purified antibodies to engender the host with short-lived immunity in serum and mucosa. In contrast, vector mediated antibody gene transfer uses a viral vector to deliver the antibody gene to the host via intramuscular injection. The antibody is produced endogenously in the muscle and secreted into the circulatory system and mucosa providing long-term protection from infection.
Figure 2
Figure 2. Antibodies vs. Immunoadhesins
A native antibody is depicted on the left, and two types of immunoadhesins are shown to the right. The immunoadhesin shown in the middle has a single-chain antibody (scFv) joined to an Fc fragment while the immunoadhesin on the right shows domain1 and domain 2 of CD4 joined to an Fc fragment.

References

    1. Getting to Zero. The Global AIDS Epidemic. Press Release. 2012
    1. Flynn NM, Forthal DN, Harro CD, et al. Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection. J Infect Dis. 2005;191:654–665. - PubMed
    1. Pitisuttithum P, Gilbert P, Gurwith M, et al. Randomized, double-blind, placebo-controlled efficacy trial of a bivalent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand. J Infect Dis. 2006;194:1661–1671. - PubMed
    1. Buchbinder SP, Mehrotra DV, Duerr A, et al. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet. 2008;372:1881–1893. - PMC - PubMed
    1. McElrath MJ, De Rosa SC, Moodie Z, et al. HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case-cohort analysis. Lancet. 2008;372:1894–1905. - PMC - PubMed

MeSH terms