I spent the best part of my 30th wedding anniversary writing a preventative neurology grant targeting EBV and infectious mononucleosis as therapeutic target to prevent MS. This is a strategic development grant for our medical school and something that brings together 15+ years of thinking and work. I am excited.
The question is does an anti-EBV vaccine have to cause sterilising immunity, i.e. prevent infection with EBV completely, or can it just prevent IM. As IM is the main risk factor for MS, simply preventing it may be sufficient to protect recipients from developing MS. If this is the case then we have thrown the baby out with the bathwater. The GSK vaccine below did just that; it prevented IM, but not wild-type EBV infection. As it did not stop wild-type EBV infection GSK stopped developing the vaccine and sold it to Medimmune. The last we heard is that Medimmune have mothballed the programme and the vaccine is not going anywhere soon. More worrying is the business case for an EBV vaccine; believe it, or not, IM & MS prevention are not sufficiently big enough to support the market for an EBV vaccine. The business case will need to be based on oncoprevention, i.e. preventing lymphomas. The scary thing is that Big Pharma need the vaccine to sell upwards of ~$2 billion per year to justify the investment in developing and producing such a vaccine. Vaccine development is a risky, and very expensive, business. As it has been shown with Ebola, and now Zika, infection the commercial development and large scale production of vaccines can only be done by Pharma. Governments simply don't have the resources, know-how and appetite for risk to take vaccine development on. Interestingly, they did in the past. What has changed? The regulatory environment and rules governing safety. Commercial vaccine development arguably one of the greatest innovations of all time is beyond is now in the hands of Pharma. Is this a good idea?
However, we have decided that we are not going to get despondent and worry about the business case. We believe that there is an unmet need for an effective anti-EBV vaccine and that human perseverance and determination will come through at the end of the day. We have a dream; 'a world free of MS'.
Sokal et al. Recombinant gp350 vaccine for infectious mononucleosis: a phase 2, randomized, double-blind, placebo-controlled trial to evaluate the safety, immunogenicity, and efficacy of an Epstein-Barr virusvaccine in healthy young adults. J Infect Dis. 2007 Dec 15;196(12):1749-53.
BACKGROUND: To date, there is no commercially available vaccine to prevent infectious mononucleosis, a disease frequently induced by Epstein-Barr virus (EBV) infection in adolescents or adults devoid of preexisting immunity to the virus.
METHODS: A total of 181 EBV-seronegative, healthy, young adult volunteers were randomized in a double-blind fashion to receive either placebo or a recombinant EBV subunit glycoprotein 350 (gp350)/aluminum hydroxide and 3-O-desacyl-4'-monophosphoryl lipid A (AS04) candidate vaccine in a 3-dose regimen.
RESULTS: The vaccine had demonstrable efficacy (mean efficacy rate, 78.0% [95% confidence interval {CI}, 1.0%-96.0%]) in preventing the development of infectious mononucleosis induced by EBV infection, but it had no efficacy in preventing asymptomatic EBV infection. One month after receipt of the final dose of gp350 vaccine, 98.7% of subjects showed seroconversion to anti-gp350 antibodies (95% CI, 85.5%-97.9%), and they remained anti-gp350 antibody positive for >18 months. Furthermore, there were no concerns regarding the safety or reactogenicity of the gp350/AS04 vaccine.
CONCLUSION: These data support the clinical feasibility of using an EBV vaccine to prevent infectious mononucleosis.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00430534.