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
. 2016 Oct 26;8(362):362ra145.
doi: 10.1126/scitranslmed.aaf9387.

A replication-defective human cytomegalovirus vaccine for prevention of congenital infection

Dai Wang  1 , Daniel C Freed  2 , Xi He  2 , Fengsheng Li  2 , Aimin Tang  2 , Kara S Cox  2 , Sheri A Dubey  2 , Suzanne Cole  2 , Muneeswara Babu Medi  2 , Yaping Liu  2 , Jingyuan Xu  2 , Zhi-Qiang Zhang  2 , Adam C Finnefrock  2 , Liping Song  2 , Amy S Espeseth  2 , John W Shiver  2 , Danilo R Casimiro  2 , Tong-Ming Fu  1
Affiliations

A replication-defective human cytomegalovirus vaccine for prevention of congenital infection

Dai Wang et al. Sci Transl Med. .

Abstract

Congenital human cytomegalovirus (HCMV) infection occurs in ~0.64% of infants born each year in the United States and is the leading nongenetic cause of childhood neurodevelopmental disabilities. No licensed HCMV vaccine is currently available. Natural immunity to HCMV in women before pregnancy is associated with a reduced risk of fetal infection, suggesting that a vaccine is feasible if it can reproduce immune responses elicited by natural infection. On the basis of this premise, we developed a whole-virus vaccine candidate from the live attenuated AD169 strain, with genetic modifications to improve its immunogenicity and attenuation. We first restored the expression of the pentameric gH/gL/pUL128-131 protein complex, a major _target for neutralizing antibodies in natural immunity. We then incorporated a chemically controlled protein stabilization switch in the virus, enabling us to regulate viral replication with a synthetic compound named Shield-1. The virus replicated as efficiently as its parental virus in the presence of Shield-1 but failed to produce progeny upon removal of the compound. The vaccine was immunogenic in multiple animal species and induced durable neutralizing antibodies, as well as CD4+ and CD8+ T cells, to multiple viral antigens in nonhuman primates.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

  NODES
Association 1
twitter 2