Work on a Cytomegalovirus Vaccine

Much of the age-related decline of the immune system can be blamed on cytomegalovirus (CMV). Near everyone is exposed to this type of herpesvirus at some point in life, and because the immune system cannot effectively clear it from the body ever more immune cells become uselessly and redundantly specialized to attack it. Since the immune system is limited in the number of cells it can support at any given time, this means that there are ever fewer cells capable of responding effectively to new threats, or patrolling the body to destroy senescent or cancerous cells.

An effective cytomegalovirus vaccine or other method of clearance and prevention will be useful for the young, and research is progressing, but this isn't an effective treatment for the old. There, the damage is already done. The best approach for rejuvenation of the immune system in this case is something along the lines of introducing new cells and destroying existing CMV-specialized cells to free up space. Nonetheless, here is an example of progress towards an effective vaccine for CMV:

Identification of immune correlates of protection for viral vaccines is complicated by multiple factors, but there is general consensus on the importance of antibodies that neutralize viral attachment to susceptible cells. Development of new viral vaccines has mostly followed this neutralizing antibody paradigm, but as a recent clinical trial of human cytomegalovirus (HCMV) vaccination demonstrated, this singular approach can yield limited protective efficacy.

Since HCMV devotes more than 50% of its coding capacity to proteins that modulate host immunity, it is hypothesized that expansion of vaccine targets to include this part of the viral proteome will disrupt viral natural history. HCMV and rhesus cytomegalovirus (RhCMV) each encode an ortholog to the cellular interleukin-10 (cIL-10) cytokine: cmvIL-10 and rhcmvIL10, respectively. Despite extensive sequence divergence from their host's cIL-10, each viral IL-10 retains nearly identical functionality to cIL-10.

Uninfected rhesus macaques were immunized with engineered, nonfunctional rhcmvIL-10 variants, which were constructed by site-directed mutagenesis to abolish binding to the cIL-10 receptor. Vaccinees developed antibodies that neutralized rhcmvIL-10 function with no cross-neutralization of cIL-10. Following subcutaneous RhCMV challenge, the vaccinees exhibited both reduced RhCMV replication locally at the inoculation site and systemically and significantly reduced RhCMV shedding in bodily fluids compared to controls. Attenuation of RhCMV infection by rhcmvIL-10 vaccination argues that neutralization of viral immunomodulation may be a new vaccine paradigm for HCMV by expanding potential vaccine targets.

Link: http://dx.doi.org/10.1128/JVI.01925-13

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