New vaccine prevents CMV infection and disease in mice

June 22, 2007

Researchers at the University of California, San Diego (UCSD) Skaggs School of Pharmacy and Pharmaceutical Sciences have patented a strategy for developing a human vaccine to prevent against Human Cytomegalovirus (hCMV) infection and disease.

CMV, a type of herpes virus, is the leading viral cause of birth defects and a serious problem in patients with compromised immune systems. The body’s natural immunity doesn’t protect against infection by the virus, estimated to be present in 50 to 75 percent of all adults.

“Until now, scientists haven’t been able to develop a vaccine to protect against CMV,” said Deborah H. Spector, Ph.D., UCSD Professor of Cellular and Molecular Medicine and faculty member of the Skaggs School of Pharmacy and Pharmaceutical Sciences. “Using a two-pronged approach, we successfully created and tested a vaccine in a mouse model with CMV that shows enormous promise for re-directing the body’s immune system, enabling it to fight the virus.”

The mouse vaccine generates an immune response that protects against both infection and development of disease when the virus is present by completely disarming the virus’s ability to replicate and establish a persistent infection. The work is currently online in advance of publication in the July issue of Journal of Virology.

“Our approach generates an immune response that is different from the normal response to the virus, and we hope to have found an ‘Achilles’ heel’ in the defenses that the virus uses to evade the immune system,” said Spector. “The virus has evolved to persist in the host by evading the immune responses either by hiding or by misdirecting the host’s immune responses. We found a way to teach the host immune system to not be tricked by the virus.” She added that the next step is to apply this strategy to create a vaccine for use in humans.

CMV is a virus that, while carried by the majority of adults in the United States, can remain dormant for years, if not the lifetime, of a healthy individual. However, two percent of all children are born with the virus passed on by the mother in utero, and 15 percent of those children will show symptoms such as hearing loss, mental retardation, motor or learning disabilities. Because the host’s natural immune system can protect from the disease but can’t rid the body of the virus, people remain infected and can become re-infected or infect others through saliva.

“Children in day care settings, for example, or adults who are sexually active, can pass along the virus,” explained Spector. “It becomes a serious problem in developing infants during the pregnancy or in those whose immune system is compromised, such as AIDS or transplant patients.”

When a persistent virus such as CMV infects an individual, it disarms the host immune system in two ways – by hiding or masking the proteins that would normally provoke an immune response, or by fooling the immune system into mounting a response that doesn’t work to eradicate the virus.

“We needed a way to make the host defense system sit up and take notice,” said Christopher S. Morello, Ph.D., first author of the study.

To do this, the researchers devised a vaccine with a one-two punch that combines a DNA immunization that targets T-cells to essential genes required for CMV replication, with a killed virus that prompts the body’s B-cells to generate an antibody response.

The vaccine contains the DNA of two essential genes that are essential for replication of the virus. These genes – which are also found in other herpes viruses such as chicken pox or herpes simplex – have the same or very similar sequence, structure and function whether in human or mouse viruses, and present a novel target for the host’s T-cells to muster forces and attack the virus. Secondly, the vaccine also contains a “boost” from an inactivated virus, which generates an antibody response. Neither approach alone would give complete protection.

“In mice, the vaccine not only fought the disease, but prevented the infection from being established in the first place,” Morello said.

Researchers at UCSD hope to begin pre-clinical work on development of a human vaccine. If successful, an FDA-approved, commercially licensed hCMV vaccine could be administered to specific at-risk populations, such as females prior to child-bearing years, day care providers, organ transplant recipients, or as part of regular childhood immunizations.

“This approach may also be valid for a number of diseases associated with persistent or latent infections, including all types of herpes-associated diseases, AIDS, or hepatitis,” said Spector. These viruses persist because immune responses generated by the viral infection are not able to eradicate the virus.

Source: University of California - San Diego

Explore further: Scientists uncover why Hepatitis C virus vaccine has been difficult to make

Related Stories

Nanoparticle vaccinates mice against dengue fever

October 20, 2016

Every year, more than 350 million people in over 120 countries contact dengue fever, which can cause symptoms ranging from achy muscles and a skin rash to life-threatening hemorrhagic fever. Researchers have struggled to ...

Zika virus infection alters human and viral RNA

October 20, 2016

Researchers at University of California San Diego School of Medicine have discovered that Zika virus infection leads to modifications of both viral and human genetic material. These modifications—chemical tags known as ...

Study sheds light on Dengue immune response

October 20, 2016

India suffers from the highest number of dengue infections in the world, but there are few studies, if any, to understand the immune cells involved in fighting the virus.

Recommended for you

Natural compound reduces signs of aging in healthy mice

October 27, 2016

Much of human health hinges on how well the body manufactures and uses energy. For reasons that remain unclear, cells' ability to produce energy declines with age, prompting scientists to suspect that the steady loss of efficiency ...

Mitochondria control stem cell fate

October 27, 2016

What happens in intestinal epithelial cells during a chronic illness? Basic research conducted at the Chair of Nutrition and Immunology at the Technical University of Munich (TUM) addressed this question by generating a new ...

Scientists develop 'world-first' 3-D mammary gland model

October 27, 2016

A team of researchers from Cardiff University and Monash Biomedicine Discovery Institute has succeeded in creating a three-dimensional mammary gland model that will pave the way for a better understanding of the mechanisms ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.