Antibody-based protection against HIV infection by vectored immunoprophylaxis
Open accessAbstract
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.
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Using viral vectors, sustained expression of low to mid microgram per milliliter levels was obtained in different models and conferred protection against influenza and RSV challenges.
“Using viral vectors, sustained expression of low to mid microgram per milliliter levels was obtained in different models and conferred protection against influenza and RSV challenges (Lewis et al, 2002; Skaricic et al, 2008; Balazs et al, 2011).”
From mRNA mediates passive vaccination against infectious agents, toxins, and tumors (2017) · cites this paper as Balazs et al, 2011
The Abstract reports sustained antibody expression after AAV-vector administration and protection at 8.3 and 34 µg/mL. But its challenge experiments used HIV, not influenza or RSV, so it does not support that part of the citing sentence. (LLM, conf=0.88)
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- Authors
- Balazs, A. B., Chen, J., Hong, C. M., Rao, D. S., Yang, L., & Baltimore, D.
- Affiliations
- California Institute of Technology (US)
- University of California, Los Angeles (US)
- Corresponding author
- Baltimore, David
- Venue
- Nature
- Published
- 2011-11-30
- Volume
- 481
- Issue
- 7379
- Pages
- 81-84
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3253190
- OpenAlex
- W2016364569
- Cited by
- 545
- References
- 38
- Citations by year
- 2026: 12 · 2025: 13 · 2024: 19 · 2023: 22 · 2022: 21 · 2021: 42 · 2020: 25 · 2019: 30 · 2018: 33 · 2017: 53 · 2016: 38 · 2015: 67 · 2014: 69 · 2013: 58 · 2012: 41
- FWCI
- 21.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- CaltechAUTHORS (California Institute of Technology) (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Bill and Melinda Gates Foundation (37866)
- amfAR, The Foundation for AIDS Research
- University of Pennsylvania
- California Institute of Technology
- National Institutes of Health (n01ai50035-4-0-0, HHSN266200500035C)
- U.S. Public Health Service (HHSN266200500035C)
- National Cancer Institute (K08CA133521)
- National Institute of Allergy and Infectious Diseases (N01 AI050035, pNL4-3, P30AI027763)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Keywords
- HIV infection, broadly neutralizing antibodies, adeno-associated virus vectors, humanized mice, HIV vaccine, intramuscular injection, prophylaxis, somatic mutations, affinity maturation
- MeSH terms
- Dependovirus, Animals, Antibodies, Monoclonal, Genetic Vectors, Humans, Immunoglobulin G, Immunization, Passive, Mice, Inbred BALB C, Mice, Inbred C57BL, HIV Antibodies, CD4-Positive T-Lymphocytes, HIV Infections, Mice, SCID, Mice, Inbred NOD, AIDS Vaccines, CD4 Lymphocyte Count, Mice, Antibodies, Neutralizing
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