In Jan 2012 a group of experts convened in the USA to identify and discuss the key issues related to the development and evaluation of human cytomegalovirus (HCMV) vaccines. It was organised by four federal agencies of the equivalent of the UK Department of Health and included:
- Leading researchers from around the world
- Pharmaceutical companies interested in manufacturing and marketing a vaccine
- Regulators (US: the Food and Drug Administration FDA, Europe: European Medicines Agency EMEA ) who will make the ultimate recommendation as to whether a vaccine is safe and effective
- US Government agencies dealing with funding, decision-making and implementation
- There are several possible candidates for a vaccine.
- There are some gaps in the current knowledge base and issues to be resolved but these can be overcome. A licenced CMV vaccine is possible for the future and there is strong support from the US Federal Government for achieving this
- However more research is needed before there is clear evidence about whether it is safe and effective to vaccinate pregnant women who catch CMV for the first time, to try and prevent transmission to their unborn baby
There are a number of candidates for a potential vaccineA vaccine is a way of priming the immune system to provide protection from disease, without subjecting the person to that disease. There are two kinds of vaccines. Passive vaccines provide ready-made immunity by given pre-formed antibodies. Active vaccines give a preparation of antigens (a substance that is foreign to the body) to stimulate a protective immune response; (the name antigen comes from generates an antibody response). Many had thought that it would be impossible to make a vaccine against CMV. This virus works by evading the immune system, so sceptics feared it would also evade a vaccine. An extra complication is that there are many different strains of CMV, and immunity to one strain does not protect you from being infected again with another strain. With other viruses, once a person has become infected, he or she typically develops antibodies against it and will not become infected again. But it appears that having CMV does not make a person completely immune to future infections, although the immune system does give some protection. Despite these challenges there are a number of different active CMV vaccines that are showing promising results. These vaccines are in different stages of trials. Phase I trials test the safety of a treatment on a small group of people and determine proper dosage. Phase II trials then test the safety and effectiveness of a therapy in larger groups. Finally, regulators require large-scale Phase III trials before they will licence a vaccine for use. CMV vaccines may be tested in Phase I and II trials on transplant patients before testing on groups of women who may become pregnant, to provide early evidence about safety.
- The first studies to produce promising results used an active vaccine with an antigen called glycoprotein B (gB). Results of a phase II trial on women of childbearing age were published in 2009 (Pass et al). Women in the vaccine group caught CMV at about half the rate of women who received a placebo.
- Studies of this same vaccine preparation in transplant patients have shown some interesting additional effects that are significant for tackling the risks of reinfection. A Phase II study of transplant patients published in 2011 (Griffiths et al) showed that the vaccine increased CMV antibodies in those who already had natural immunity. This is important because these antibodies can help control infections like CMV which directly target the immune system. It also had a significant impact on reducing re-infection in transplant patients who had already had CMV and received an organ from a donor who had also had CMV before. This means that it boosted immunity to other strains.
- A phase II study of a different vaccine in transplant patients reported in Jan 2012 (Kharfan-Dabaja et al), strengthening the evidence that HCMV vaccines could be effective.
Key stakeholders are now positive about the potential to develop a vaccine for congenital CMVDuring the course of this event attendees discussed a number of specific issues including:
- Which babies are most at risk of being born with congenital CMV?
- What should the goal of a phase III trial be? To reduce CMV infection rates in pregnant women, to reduce the proportion of children born with CMV or to reduce the health burden of congenital CMV?
- Which group to target a phase III trial on? Teenagers, women of childbearing age, toddlers?
- Who should you ultimately aim to vaccinate? Teenagers, toddlers or mums to be? Males as well as females?
- What proportion of the population would you need to vaccinate in order to wipe out CMV?