title: Prior population immunity reduces the expected impact of CTL-inducing vaccines for pandemic influenza control.
abstract: Vaccines that trigger an influenza-specific cytotoxic T cell (CTL) response may aid pandemic control by limiting the transmission of novel influenza A viruses (IAV). We consider interventions with hypothetical CTL-inducing vaccines in a range of epidemiologically plausible pandemic scenarios. We estimate the achievable reduction in the attack rate, and, by adopting a model linking epidemic progression to the emergence of IAV variants, the opportunity for antigenic drift. We demonstrate that CTL-inducing vaccines have limited utility for modifying population-level outcomes if influenza-specific T cells found widely in adults already suppress transmission and prove difficult to enhance. Administration of CTL-inducing vaccines that are efficacious in "influenza-experienced" and "influenza-naive" hosts can likely slow transmission sufficiently to mitigate a moderate IAV pandemic. However if neutralising cross-reactive antibody to an emerging IAV are common in influenza-experienced hosts, as for the swine-variant H3N2v, boosting CTL immunity may be ineffective at reducing population spread, indicating that CTL-inducing vaccines are best used against novel subtypes such as H7N9. Unless vaccines cannot readily suppress transmission from infected hosts with naive T cell pools, targeting influenza-naive hosts is preferable. Such strategies are of enhanced benefit if naive hosts are typically intensively mixing children and when a subset of experienced hosts have pre-existing neutralising cross-reactive antibody. We show that CTL-inducing vaccination campaigns may have greater power to suppress antigenic drift than previously suggested, and targeting adults may be the optimal strategy to achieve this when the vaccination campaign does not have the power to curtail the attack rate. Our results highlight the need to design interventions based on pre-existing cellular immunity and knowledge of the host determinants of vaccine efficacy, and provide a framework for assessing the performance requirements of high-impact CTL-inducing vaccines.
authors: School of Mathematical Sciences, University of Nottingham, Nottingham, United Kingdom; School of Community Health Sciences, University of Nottingham, Nottingham, United Kingdom.
authors: Kirsty J
authors: KJ
authors: Bolton
authors: Vaccine and Immunisation Research Group, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia; Murdoch Childrens Research Institute, Melbourne, Australia.
authors: James M
authors: JM
authors: McCaw
authors: Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia.
authors: Lorena
authors: L
authors: Brown
authors: Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia.
authors: David
authors: D
authors: Jackson
authors: Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia.
authors: Katherine
authors: K
authors: Kedzierska
authors: Vaccine and Immunisation Research Group, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia; Murdoch Childrens Research Institute, Melbourne, Australia.
authors: Jodie
authors: J
authors: McVernon
mesh_terms: D000465:Algorithms; D006801:Humans; D007109:Immunity; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology* / Q000517:prevention & control*; D015233:Models, Statistical; D058873:Pandemics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination
chemical_list: D007252:Influenza Vaccines