The changing zeitgeist of CMV vaccines

     

Professor Paul Griffiths

Professor of Virology, University College London

CMV represents a very real public health concern.
This virus damages more babies than many better known infections and every year one or two in every  200 babies are born with CMV.1
This makes CMV the most common infection passed from mother to her baby.

Sadly, around one in every five of these babies will have problems as a result of congenital CMV infection.2 These include vision loss, cerebral palsy, epilepsy, physical impairment, as well as behavioural and learning difficulties. In addition, some 13 per cent of babies born with CMV develop hearing loss,3 and at a quarter of all cases, CMV infection is the leading cause of preventable hearing loss in childhood.4

Clearly these problems can place considerable burdens on the affected child and their family. But they also place burdens on health, social and educational services. The cost to the NHS of hearing loss, for example, is significant; the hearing loss associated with CMV infection is frequently progressive, with the commonest severity being severe-profound, for which the lifelong cost of a cochlear implant is £82,000 - £108,000.5

Similarly, the cost of the provision of specialist health care for other conditions caused by CMV can be high. The total cost of care for epilepsy conditions is around £2billion in direct and indirect costs,6 and the annual recurrent cost of NICE recommended care for ADHD around £40million.7 If we add to this the costs of NHS care for vision loss, cerebral palsy, developmental problems and the many other conditions caused by CMV, the total burden rises even further. 

Of course, eradication of CMV will not completely remove all of these costs—since they can all be caused by other diseases—but they would at least remove an important preventable component of the overall total. Health economic assessments are needed to more accurately determine some of these burdens.

One by one, the scourges of polio, measles, mumps and rubella began to be eliminated in many countries. In terms of public health, CMV was an obvious early candidate for a vaccine. It damaged many more babies each year than did rubella for example, and the costs of treating the consequences are high. Unfortunately, for various reasons, a suitable vaccine was not quickly identified and researchers turned their attention to making successful vaccines against viruses like hepatitis A, hepatitis B, rotavirus and chickenpox. 

Over the decades few researchers showed enthusiasm for tackling the problem of CMV.
It was seen as too complex a virus because it infected each person more than once and can lie dormant or latent for years before reawakening to cause recurrent infections in some. The molecular biology of the virus itself showed it to be adept at evading the human immune system and many argued it would simply be “impossible” to make a vaccine against CMV.

Nevertheless, some investigators persisted, citing the need for evidence before giving up on such an important cause of disease. And their persistence is showing encouraging signs of being rewarded. 

The results of three studies in particular have been reported in recent years8,9,10 and, while none of the vaccines was good enough to yet offer to the general public, there are at least some signs now that there is the potential for making improvements through further development and additional clinical trials. Some of these are so-called ‘Phase 1’ (very early) studies, but there is now at least one vaccine in ‘Phase 3’ trials—the type of large-scale study from which regulatory bodies are able to determine whether the vaccine should be made available to the general public. So it seems that some progress is being made.

So is there anything that the public can do to help? The good news is that they can get involved with family members, friends and neighbours to take part in randomised controlled trials. Tens of thousands of volunteers will eventually be needed including toddlers, teenagers of both sexes and women of childbearing age. These studies take time but they will provide the best way of ensuring that a CMV vaccine is being given a fair chance to demonstrate its safety and efficacy. 

How long will it take before we have a vaccine to routinely protect against the terrible effects of congenital CMV, just as we now routinely protect against the effects of measles, mumps, rubella and polio? Realistically, it will need years or even decades, and we don’t know how many vaccine candidates will have to be evaluated before one is found that is good enough to be licensed. But the zeitgeist has definitely changed from when it was deemed “impossible”, we now talk not of “if we get a CMV vaccine” but “when we get a CMV vaccine”. The future may not be now, but it’s getting very much closer.

 

Public education

  • In the US, the Centers for Disease Control and Prevention (CDC) recommends doctors tell pregnant women about CMV and is investing in a public education programme
  • The state of Utah have made CMV education mandatory and Hawaii’s legislature recently took the first step in passing their proposed law on communicating the dangers of CMV to pregnant women. Similar legislation is being considered in a number of other states including Connecticut, Illinois, Tennessee and Texas
  • Professional and Public Health bodies across several other countries recommend that health professionals educate women about CMV. For example, The Australian Society for Infectious Diseases (ASID) recommends CMV counselling at prenatal and antenatal appointments. In France, the ANAES (Agence Nationale d’Accréditation et d’Evaluation en Santé) and CSHPF (Conseil supérieur d’hygiène publique de France) also recommend giving information to pregnant women about CMV infection
  • There are no recommendations in the UK for antenatal education

Antenatal screening

  • Testing of pregnant women is controversial and its use is not recommended in the UK or US
  • However, Israel and eight European countries (France, Belgium, Spain, Italy, Germany, Austria, Portugal and the Netherlands) routinely screen the majority of pregnant women serologically for CMV.11 This routine serologic screening occurs without the recommendations or guidelines of any governmental agency, authority or professional medical society

Screening of neonates 

  • Screening programmes for newborns have not yet been implemented at national level in the US or Europe but there is increasing enthusiasm for this among health care professionals
  • In the US, a large study is evaluating whether CMV screening should be routinely implemented and the feasibility of such a programme
  • In the state of Utah CMV testing is mandatory for newborns who fail their hearing screen and other states are planning a similar approach

Other healthcare guidelines 

  • In the US, the Institute of Medicine has ranked the development of a CMV vaccine as one of their highest priorities because of the lives it would save and the disabilities it would prevent. However, it may be a number of years before there is a Food and Drug Administration-approved CMV vaccine
  • In the UK, health technology assessment bodies such as the National Institute for Health and Care Excellence (NICE) and the Scottish Medicines Consortium (SMC) have no current plans to update guidelines involving CMV
 
     

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