title: Rabies pre-exposure prophylaxis elicits long-lasting immunity in humans.
abstract: Despite the availability of safe and effective human vaccines, rabies remains a global threat, with an estimated 60,000 human deaths annually attributed to rabies. Pre-exposure prophylaxis against rabies infection is recommended for travelers to countries where rabies is endemic, and also for those with a higher risk of exposure. In this study, the rabies-specific neutralising antibody responses in a cohort of rabies-vaccinated recipients over a period of twenty years have been assessed. In particular, the antibody response to primary vaccinations and boosters, and the waning of antibody post primary vaccination and post booster were investigated. The significance of gender, age at vaccination, vaccine manufacturer and vaccination intervals were also evaluated. These data confirm that rabies vaccination can elicit a neutralising antibody response that can remain at detectable levels for a number of years, without additional booster vaccinations. The antibody response following both primary vaccination and booster was significantly influenced by the gender of the subject (p=0.002 and 0.03 respectively), with supportive data that suggests an effect by the make of vaccine administered following primary vaccination, with significantly higher VNA titres observed for one vaccine manufactured prior to 2006 (p<0.001) in a small subset of recipients (n=5). Additionally, the decay rate was demonstrated through the overall decline in antibody titre for all individuals, which was a 37% and 27% reduction per 2-fold change in time following primary and booster vaccination respectively. Individuals within older age groups demonstrated a significantly faster decline in antibody titre following the primary vaccination course (p=0.012). Rate of decline in antibody titre was also significantly influenced by the vaccine make following primary course (p<0.001). The assessment of neutralising antibody titre decline has also provided an insight into the most appropriate timing for booster administration, and enabled the prediction of long term titres from post-vaccination antibody titres.
authors.affiliation: Wildlife Zoonoses and Vector-borne Diseases Research Group, Animal and Plant Health Agency (APHA), UK; Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Mansfield
authors.affiliation: Statistics, Modelling and Economics Department, National Infection Service, Public Health England (PHE), London, UK.
authors.forename: Nick
authors.initials: N
authors.lastname: Andrews
authors.affiliation: Wildlife Zoonoses and Vector-borne Diseases Research Group, Animal and Plant Health Agency (APHA), UK.
authors.forename: Hooman
authors.initials: H
authors.lastname: Goharriz
authors.affiliation: Wildlife Zoonoses and Vector-borne Diseases Research Group, Animal and Plant Health Agency (APHA), UK.
authors.forename: Trudy
authors.initials: T
authors.lastname: Goddard
authors.affiliation: Wildlife Zoonoses and Vector-borne Diseases Research Group, Animal and Plant Health Agency (APHA), UK; Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
authors.forename: Lorraine M
authors.initials: LM
authors.lastname: McElhinney
authors.affiliation: Virus Reference Department, National Infection Service, Public Health England (PHE), London, UK.
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Brown
authors.affiliation: Wildlife Zoonoses and Vector-borne Diseases Research Group, Animal and Plant Health Agency (APHA), UK; Institute of Infection and Global Health, University of Liverpool, Liverpool, UK; Institute for Infection and Immunity, St. George's Hospital Medical School, University of London, London, UK. Electronic address: Tony.Fooks@apha.gsi.gov.uk.
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Fooks
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D015331:Cohort Studies; D019353:Endemic Diseases / Q000517:prevention & control; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007271:Injections, Intradermal; D008297:Male; D065129:Pre-Exposure Prophylaxis; D011818:Rabies / Q000276:immunology* / Q000517:prevention & control; D011819:Rabies Vaccines / Q000008:administration & dosage / Q000276:immunology*; D012737:Sex Factors; D013997:Time Factors; D014195:Travel; D064166:Vaccine Potency
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D011819:Rabies Vaccines
keywords: Antibody titre; Longevity; Pre-exposure prophylaxis; Rabies; VNA; Vaccination