气候变化领域集成服务门户(CCPortal): Adenovirus-vectored vaccine containing multidimensionally conserved parts of the HIV proteome is immunogenic in rhesus macaques

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DOI	10.1073/PNAS.2022496118
	Adenovirus-vectored vaccine containing multidimensionally conserved parts of the HIV proteome is immunogenic in rhesus macaques
	Murakowski D.K.; Barton J.P.; Peter L.; Chandrashekar A.; Bondzie E.; Gao A.; Barouch D.H.; Chakraborty A.K.
发表日期	2021
ISSN	00278424
卷号	118 期号:5
英文摘要	An effective vaccine that can protect against HIV infection does not exist. A major reason why a vaccine is not available is the high mutability of the virus, which enables it to evolve mutations that can evade human immune responses. This challenge is exacerbated by the ability of the virus to evolve compensatory mutations that can partially restore the fitness cost of immune-evading mutations. Based on the fitness landscapes of HIV proteins that account for the effects of coupled mutations, we designed a single long peptide immunogen comprising parts of the HIV proteome wherein mutations are likely to be deleterious regardless of the sequence of the rest of the viral protein. This immunogen was then stably expressed in adenovirus vectors that are currently in clinical development. Macaques immunized with these vaccine constructs exhibited T-cell responses that were comparable in magnitude to animals immunized with adenovirus vectors with whole HIV protein inserts. Moreover, the T-cell responses in immunized macaques strongly targeted regions contained in our immunogen. These results suggest that further studies aimed toward using our vaccine construct for HIV prophylaxis and cure are warranted. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Fitness landscape; HIV; Subunit vaccines
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/181186
作者单位	Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard University, Cambridge, MA 02139, United States; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States; Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, United States
推荐引用方式 GB/T 7714	Murakowski D.K.,Barton J.P.,Peter L.,et al. Adenovirus-vectored vaccine containing multidimensionally conserved parts of the HIV proteome is immunogenic in rhesus macaques[J],2021,118(5).
APA	Murakowski D.K..,Barton J.P..,Peter L..,Chandrashekar A..,Bondzie E..,...&Chakraborty A.K..(2021).Adenovirus-vectored vaccine containing multidimensionally conserved parts of the HIV proteome is immunogenic in rhesus macaques.Proceedings of the National Academy of Sciences of the United States of America,118(5).
MLA	Murakowski D.K.,et al."Adenovirus-vectored vaccine containing multidimensionally conserved parts of the HIV proteome is immunogenic in rhesus macaques".Proceedings of the National Academy of Sciences of the United States of America 118.5(2021).