With all the hype regarding COVID-19 and a vaccine that may or may not be coming soon, we can use the story of RSV as an object lesson. Why do we give passive immunization to preterm infants against RSV rather than a vaccine?
RSV vaccines have been produced in the past, but there was significantly worse illness among babies who became infected despite vaccination. The vaccine was an inactivated virus but triggered “a nonprotective antibody response and CD4+ T helper priming in the absence of cytotoxic T lymphocytes. This response to vaccination led to a pathogenic Th2 memory response with eosinophil and immune complex deposition in the lungs after RSV infection”. Which is a phrase that I quote directly from (Acosta PL, et al. Brief History and Characterization of Enhanced Respiratory Syncytial Virus Disease. Clin Vaccine Immunol. 2015;23(3):189-95.) because I understand little of it, immunology was invented after I went to medical school.
Anyway, I can understand that under certain circumstances a vaccine could make things worse. As far as I can see, the trials in which the enhanced disease that occurred in vaccinated children led to the trials being stopped, and I don’t think a vaccine has ever actually been licensed as a result. Which makes me grateful for the FDA and other agencies around the world that require good evidence prior to the widespread use of a drug or vaccine. (In contrast to the claims of the antivaxers). So prior to rushing to introduce a vaccine for COVID-19 we need to be sure that it is safe and effective. Especially as severe cases of COVID seem to be associated with excessive immune responses, so there is a real possibility that a vaccine could make things worse at least for some recipients.
Newer candidate RSV vaccines will also have to be tested in adequate trials before we can be confident that they work and are safe. Vaccinating mothers is one possible way of getting around some of the problems, (Madhi SA, et al. Respiratory Syncytial Virus Vaccination during Pregnancy and Effects in Infants. N Engl J Med. 2020;383(5):426-39), However in this trial among 4,500 mothers who either received a vaccine based on the RSV fusion protein (F) or a placebo at between 28 and 36 weeks gestation, the overall reduction in clinically significant RSV disease in their infants during their first 90 days of life was from 2.4 to 1.5%. Which was not enough to conclude adequate efficacy, there were some signs of benefit, in terms of hospitalisations and severe disease, but not much more than about a 40% reduction for either.
For now then, I think we will be continuing with passive immunization while other candidate RSV vaccines (and there appear to be several) are being tested. Unfortunately that currently means monthly IM palivizumab injections at an exorbitant price, and a lot of discomfort. One improvement in passive immunization would be an antibody with a much lower clearance, such as this one (Griffin MP, et al. Single-Dose Nirsevimab for Prevention of RSV in Preterm Infants. N Engl J Med. 2020;383(5):415-25) so that a single dose would last the whole RSV season. In this trial, 1453 infants who had been born preterm (29 to <35 weeks gestation) but were not eligible for RSV prophylaxis according to their local guidelines were randomized to receive one dose of the new long-acting antibody nirsevimab, or placebo in a 2:1 ratio, if they were under 1 year of age at the start of RSV season. The primary outcome was the occurrence of RSV disease needing medical attention during the first 180 days, which was substantially reduced from 9,5% to 2.6%, and hospitalizations for RSV bronchiolitis were reduced from 4.1 to 0.8%.
I have little trust when it comes to big pharma, and I give you this prediction, that nirsevimab will cost substantially more than palivizumab. Probably the producers will calculate the average number of doses of palivizumab that babies receive (which is probably about 3.5) they will then price nirsevimab to be 3.5 times more expensive than palivizumab, so that they will be able to tell you that there is a substantial saving in resources with the new drug (which would be true), and a reduction in pain and discomfort, but they will still be able to screw our health systems for as much profit as they possibly can! I used to think that drug pricing was based on development and production costs, with a profit margin added; how naive! Drug prices are based on the principle of AMAWCGAW (as much as we can we get away with, ©Barrington 2020), and I can’t see AzstraZeneca and Sanofi Pasteur deviating from that time-honoured principle.
I would love to be proved wrong.