Recent advances in designing an effective vaccine to prevent cytomegalovirus-associated clinical diseases

Abstract

It is now well over a decade since the US Institute of Medicine of the National Academy of Sciences assigned the highest priority for a vaccine to prevent congenital human CMV infection, which was subsequently endorsed by the US National Vaccine Program Office. In spite of extensive efforts over many years, successful licensure of a CMV vaccine formulation remains elusive. While the understanding of immune regulation of CMV infection in healthy virus carriers and diseased patients has dramatically improved, traditional vaccine development programs have failed to exploit this knowledge. Until recently, most efforts have concentrated on designing vaccine formulations that block CMV infection through neutralizing antibodies. However, studies carried out in various disease settings, especially in transplant patients, have clearly emphasized the importance of cellular immunity and it is indeed encouraging to see that recent CMV vaccine development programs have started to incorporate this arm of the immune system. A number of new vaccine candidates have been found to be effective in preclinical studies, and are able to induce CMV-specific immune responses in clinical studies, although firm evidence for long-term efficacy is not yet available. For successful implementation of these vaccines in clinical settings, it will be important to demonstrate that the vaccine can induce effective levels of immunity for prevention of transmission of viral infection from mother to unborn baby and thus reduce CMV-related pathogenesis. For transplant recipients, vaccine strategies should be aimed at the induction of immunity that restricts viral reactivation and limits development of disease.

Keywords::

• antibody
• congenital infection
• epitopes
• herpes virus
• human cytomegalovirus
• prevention of CMV disease
• prophylactic vaccine
• T cells
• transplant
• vaccination

Financial & competing interests disclosure

This work is supported by a grant funding by the National Health and Medical Research Council (NHMRC) Australia and Cancer Council Queensland. R Khanna is supported by a Senior Principal Research Fellowship from NHMRC. R Khanna and V Dasari are listed as inventors on international patents and patent applications on the development of cytomegalovirus vaccine. These patents includes a broad range of cytomegalovirus T-cell epitopes and polyepitope technology. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.