Abstract: Vaccines have been a major factor in the improvement in childhood mortality in the last 200 years. This can be seen in the excellent informatics on https://www.gapminder.org/tools/ (set X-axis to time and Y-axis to life expectancy and then childhood mortality).
Whooping cough used to be a major cause of infant death, but incidence was greatly reduced by the introduction of a killed whole-bacteria vaccine in the late 1950s. In the mid-1970s there was an anti- vaccine whooping cough story in the UK media. Vaccine uptake declined precipitously, and disease increased dramatically. Owing to lack of confidence in the vaccine, a safer ‘acellular’ vaccine was developed and shown to protect against severe disease in infants in large gold-standard placebo-controlled phase III clinical trials in countries that no longer used a whooping cough vaccine and consequently had high incidence of this disease. An unintended consequence of the new acellular vaccine was reduced ability to control colonisation and transmission, resulting in a resurgence of whooping cough in many developed countries using this vaccine (including the UK with 10,000 cases in 2012) and a change in the age profile to disease in older children and adults. Traditional efficacy trials will not be possible to evaluate new vaccines as the current vaccine will continue to be used. Thus, understanding immune correlates of protection and controlled human infection studies are being developed to provide multiple strands of evidence for licensure. The lessons that the whooping cough story has for the development of new vaccines, including to prevent Covid-19, will be discussed.

Biography: Andrew Gorringe is a Scientific Leader at Public Health England, Porton Down and a Visiting Professor at the University of Bath. He leads a research group that is focussed on the assessment of vaccine immune responses, particularly for whooping cough, meningitis and Group B Streptococcus vaccines. He is interested in developing ways of measuring immune responses that correlate with protection against disease. He has been involved in vaccine research since the early 1980s, completing PhD on research that contributed to the development of a subunit whooping cough vaccine similar to that used in UK infants since 2004. Research then changed to focus on serogroup B meningococcal disease, and he led the development of a vaccine that was assessed in a phase I clinical trial. He has collaborated on an experimental infection of adult volunteers with the harmless bacterium Neisseria lactamica. This showed that experimental colonisation with this commensal reduced carriage and new acquisition of the pathogen Neisseria meningitidis. The resurgence of whooping cough seen in some countries was an alert to the lack of understanding of immune responses that protect against this disease, and this is now an active area of research as part of the European Union PERISCOPE consortium. His group are developing new functional antibody assays and collaborating on the development of a whooping cough human challenge model with Professor Robert Read (University of Southampton). The laboratories at PHE Porton Down have responded to the Covid-19 pandemic by moving almost entirely to research on this disease. Andrew Gorringe has been involved with vaccine assessment studies and is a member of a WHO group co-ordinating antibody prevalence studies.