The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Neutralizing Antibodies to Adenovirus Serotype 5 Vaccine Vectors Are Directed Primarily against the Adenovirus Hexon Protein
Abstract
The utility of recombinant adenovirus serotype 5 (rAd5) vector-based vaccines for HIV-1 and other pathogens will likely be limited by the high prevalence of pre-existing Ad5-specific neutralizing Abs (NAbs) in human populations. However, the immunodominant targets of Ad5-specific NAbs in humans remain poorly characterized. In this study, we assess the titers and primary determinants of Ad5-specific NAbs in individuals from both the United States and the developing world. Importantly, median Ad5-specific NAb titers were >10-fold higher in sub-Saharan Africa compared with the United States. Moreover, hexon-specific NAb titers were 4- to 10-fold higher than fiber-specific NAb titers in these cohorts by virus neutralization assays using capsid chimeric viruses. We next performed adoptive transfer studies in mice to evaluate the functional capacity of hexon- and fiber-specific NAbs to suppress the immunogenicity of a prototype rAd5-Env vaccine. Hexon-specific NAbs were remarkably efficient at suppressing Env-specific immune responses elicited by the rAd5 vaccine. In contrast, fiber-specific NAbs exerted only minimal suppressive effects on rAd5 vaccine immunogenicity. These data demonstrate that functionally significant Ad5-specific NAbs are directed primarily against the Ad5 hexon protein in both humans and mice. These studies suggest a potential strategy for engineering novel Ad5 vectors to evade dominant Ad5-specific NAbs.
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Novel approaches for vaccine development
Gebre, M. S., Brito, L. A., Tostanoski, L. H., Edwards, D. K., Carfi, A., & Barouch, D. H. (2021) · Cell · doi:10.1016/j.cell.2021.02.030 · Cited by 347
Self-citationPre-existing immunity against Ad vectors: Humoral, cellular, and innate response, what's important?
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Adenoviral Vector Immunity: Its Implications and Circumvention Strategies
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Metadata
- Authors
- Sumida, S. M., Truitt, D. M., Lemckert, A. A. C., Vogels, R., Custers, J. H. H. V., Addo, M. M., Lockman, S., Peter, T., Peyerl, F. W., Kishko, M. G., Jackson, S. S., Gorgone, D. A., Lifton, M. A., Essex, M., Walker, B. D., Goudsmit, J., Havenga, M. J. E., & Barouch, D. H.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-06-01
- Volume
- 174
- Issue
- 11
- Pages
- 7179-7185
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2164806280
- Cited by
- 369
- References
- 31
- FWCI
- 11.60
- Type
- journal article
- Language
- en
- Open access
- closed
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- Sumida, S. M., Truitt, D. M., Lemckert, A. A. C., Vogels, R., Custers, J. H. H. V., Addo, M. M., Lockman, S., Peter, T., Peyerl, F. W., Kishko, M. G., Jackson, S. S., Gorgone, D. A., Lifton, M. A., Essex, M., Walker, B. D., Goudsmit, J., Havenga, M. J. E., & Barouch, D. H. (2005). Neutralizing Antibodies to Adenovirus Serotype 5 Vaccine Vectors Are Directed Primarily against the Adenovirus Hexon Protein. The Journal of Immunology. https://doi.org/10.4049/jimmunol.174.11.7179
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
