Publication Date:
2011-12-06
Description:
Despite tremendous efforts, development of an effective vaccine against human immunodeficiency virus (HIV) has proved an elusive goal. Recently, however, numerous antibodies have been identified that are capable of neutralizing most circulating HIV strains. These antibodies all exhibit an unusually high level of somatic mutation, presumably owing to extensive affinity maturation over the course of continuous exposure to an evolving antigen. Although substantial effort has focused on the design of immunogens capable of eliciting antibodies de novo that would target similar epitopes, it remains uncertain whether a conventional vaccine will be able to elicit analogues of the existing broadly neutralizing antibodies. As an alternative to immunization, vector-mediated gene transfer could be used to engineer secretion of the existing broadly neutralizing antibodies into the circulation. Here we describe a practical implementation of this approach, which we call vectored immunoprophylaxis (VIP), which in mice induces lifelong expression of these monoclonal antibodies at high concentrations from a single intramuscular injection. This is achieved using a specialized adeno-associated virus vector optimized for the production of full-length antibody from muscle tissue. We show that humanized mice receiving VIP appear to be fully protected from HIV infection, even when challenged intravenously with very high doses of replication-competent virus. Our results suggest that successful translation of this approach to humans may produce effective prophylaxis against HIV.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3253190/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3253190/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Balazs, Alejandro B -- Chen, Joyce -- Hong, Christin M -- Rao, Dinesh S -- Yang, Lili -- Baltimore, David -- 1K08CA133521/CA/NCI NIH HHS/ -- HHSN266200500035C/PHS HHS/ -- K08 CA133521/CA/NCI NIH HHS/ -- N01AI50035/AI/NIAID NIH HHS/ -- England -- Nature. 2011 Nov 30;481(7379):81-4. doi: 10.1038/nature10660.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22139420" target="_blank"〉PubMed〈/a〉
Keywords:
AIDS Vaccines/administration & dosage/genetics/*immunology
;
Animals
;
Antibodies, Monoclonal/genetics/immunology
;
Antibodies, Neutralizing/genetics/*immunology
;
CD4 Lymphocyte Count
;
CD4-Positive T-Lymphocytes/cytology/immunology
;
Dependovirus/genetics/immunology
;
Genetic Vectors/administration & dosage/*genetics
;
HIV Antibodies/genetics/*immunology
;
HIV Infections/*immunology/*prevention & control
;
Humans
;
Immunization, Passive/*methods
;
Immunoglobulin G/genetics/immunology
;
Mice
;
Mice, Inbred BALB C
;
Mice, Inbred C57BL
;
Mice, Inbred NOD
;
Mice, SCID
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
