Quantifying Protection Against Influenza Virus Infection Measured by Hemagglutination-inhibition Assays in Vaccine Trials. 2016

Xiahong Zhao, and Vicky J Fang, and Suzanne E Ohmit, and Arnold S Monto, and Alex R Cook, and Benjamin J Cowling
From the aSaw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore; bLi Ka Shing Faculty of Medicine, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region, China; cDepartment of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI; and dYale-NUS College, National University of Singapore, Singapore, Singapore.

BACKGROUND Correlations between hemagglutination-inhibition titers (hereafter "titers") and protection against infection have been identified in historical studies. However, limited information is available about the dynamics of how titer influences protection. METHODS Titers were measured in randomized, placebo-controlled vaccine trials in Hong Kong among pediatrics during September 2009-December 2010 and the United States among adults during Oct 2007-April 2008. Intermediate unobserved titers were imputed using three interpolation methods. As participants were recruited at different times leading to varying exposure to infection relative to entry, a modified proportional hazards model was developed to account for staggered entry into the studies and to quantify the correlation of titers with protection against influenza infections, adjusting for waning in titers. The model was fitted using Markov chain Monte Carlo and importance sampling. RESULTS A titer of 1:40 was associated with a reduced infection risk of 40%-70% relative to a titer of 1:10, depending on the circulating strain; the corresponding protection associated with a titer of 1:80 was 54%-84%. Results were robust across interpolation methods. The trivalent-inactivated vaccine reduced cumulative incidence of influenza B and influenza A(H3N2) infections by six percentage points (pp; 95% credible interval = 2 pp, 10 pp) and 1 pp (95% credible interval = 0.3 pp, 2 pp) respectively, but not for influenza A(H1N1)pdm09. The live-attenuated vaccine showed little efficacy against influenza A(H3N2) infections. CONCLUSIONS Titers are correlated with protection against influenza infections. The trivalent inactivated vaccine can reduce the risk of influenza A(H3N2) and influenza B infections in the community.

UI MeSH Term Description Entries
D007251 Influenza, Human An acute viral infection in humans involving the respiratory tract. It is marked by inflammation of the NASAL MUCOSA; the PHARYNX; and conjunctiva, and by headache and severe, often generalized, myalgia. Grippe,Human Flu,Human Influenza,Influenza in Humans,Influenza,Flu, Human,Human Influenzas,Influenza in Human,Influenzas,Influenzas, Human
D007252 Influenza Vaccines Vaccines used to prevent infection by viruses in the family ORTHOMYXOVIRIDAE. It includes both killed and attenuated vaccines. The composition of the vaccines is changed each year in response to antigenic shifts and changes in prevalence of influenza virus strains. The flu vaccines may be mono- or multi-valent, which contains one or more ALPHAINFLUENZAVIRUS and BETAINFLUENZAVIRUS strains. Flu Vaccine,Influenzavirus Vaccine,Monovalent Influenza Vaccine,Universal Flu Vaccine,Universal Influenza Vaccine,Flu Vaccines,High-Dose Trivalent Influenza Vaccine,Influenza Vaccine,Influenza Virus Vaccine,Influenza Virus Vaccines,Influenzavirus Vaccines,Intranasal Live-Attenuated Influenza Vaccine,LAIV Vaccine,Monovalent Influenza Vaccines,Quadrivalent Influenza Vaccine,Trivalent Influenza Vaccine,Trivalent Live Attenuated Influenza Vaccine,Universal Flu Vaccines,Universal Influenza Vaccines,Flu Vaccine, Universal,High Dose Trivalent Influenza Vaccine,Influenza Vaccine, Monovalent,Influenza Vaccine, Quadrivalent,Influenza Vaccine, Trivalent,Influenza Vaccine, Universal,Intranasal Live Attenuated Influenza Vaccine,Vaccine, Flu,Vaccine, Influenza,Vaccine, Influenza Virus,Vaccine, Influenzavirus,Vaccine, LAIV,Vaccine, Monovalent Influenza,Vaccine, Quadrivalent Influenza,Vaccine, Trivalent Influenza,Virus Vaccine, Influenza
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009981 Influenza B virus Species of the genus BETAINFLUENZAVIRUS that cause HUMAN INFLUENZA and other diseases primarily in humans. Antigenic variation is less extensive than in type A viruses (INFLUENZA A VIRUS) and consequently there is no basis for distinct subtypes or variants. Epidemics are less likely than with INFLUENZA A VIRUS and there have been no pandemics. Previously only found in humans, Influenza B virus has been isolated from seals which may constitute the animal reservoir from which humans are exposed. Betainfluenzavirus influenzae,FLUBV,Human Influenza B Virus,Influenza Viruses Type B,Influenza virus type B,Orthomyxoviruses Type B,Influenza B viruses
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D005260 Female Females
D006385 Hemagglutination Inhibition Tests Serologic tests in which a known quantity of antigen is added to the serum prior to the addition of a red cell suspension. Reaction result is expressed as the smallest amount of antigen which causes complete inhibition of hemagglutination. Hemagglutination Inhibition Test,Inhibition Test, Hemagglutination,Inhibition Tests, Hemagglutination,Test, Hemagglutination Inhibition,Tests, Hemagglutination Inhibition
D006723 Hong Kong The former British crown colony located off the southeast coast of China, comprised of Hong Kong Island, Kowloon Peninsula, and New Territories. The three sites were ceded to the British by the Chinese respectively in 1841, 1860, and 1898. Hong Kong reverted to China in July 1997. The name represents the Cantonese pronunciation of the Chinese xianggang, fragrant port, from xiang, perfume and gang, port or harbor, with reference to its currents sweetened by fresh water from a river west of it. Kowloon,New Territories,Hongkong
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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