Despite high levels of vaccine mismatch, an inactivated quadrivalent influenza vaccine (IIV4) may prevent influenza A and B in children aged 6 to 35 months, according to a study recently published in the Lancet Child & Adolescent Health.
This phase 3 study (ClinicalTrials.gov identifier: NCT01439360) aimed to fill the evidence gap among children aged 6 to 35 months by investigating the efficacy and healthcare effects of an IIV4. Because traditional trivalent vaccines only contain 1 B strain, a quadrivalent vaccine was used that contains 2 A strains (H1N1 and H3N2) and both B strains (Yamagata and Victoria), offering broader protection.
A total of 12,018 children in 13 temperate and subtropical countries were recruited in 5 independent cohorts between 2011 and 2014. Healthy children were eligible, irrespective of influenza vaccination in previous seasons. Children were randomly assigned (1:1) to receive either IIV4 (n=6006) or 1 of the following control vaccines (n=6012): pneumococcal conjugate vaccine, hepatitis A vaccine, or varicella vaccine. Surveillance for influenza-like episodes began for each individual child from 14 days after their final vaccination until the end of the influenza season.
Efficacy was in relation to whether the vaccine was matched or mismatched to circulating strains over the course of 5 influenza seasons. A vaccine-matched strain was defined as up to 4-fold difference in hemagglutination-inhibiting or hemagglutination-neutralizing antibody titers relative to a reference serum; a mismatch was defined as >4-fold difference. For each influenza episode, a nasal swab was collected within 7 days, influenza virus A or B was determined via RT polymerase chain reaction, and results were reported as either matched or mismatched to the vaccine strain.
Vaccine efficacy was seen despite substantial mismatch between strains contained in the vaccine and those circulating in the community. At least 1 case of RT polymerase chain reaction-confirmed influenza was reported in 356 (6%) children in the IIV4 group and 693 (12%) children in the control group. Of the 1049 influenza strains, 138 (13%) were A/H1N1, 529 (50%) were A/H3N2, 69 (7%) were B/Victoria, and 316 (30%) were B/Yamagata. Overall, mean titer of hemagglutination-inhibiting antibodies increased 9- to 17-fold against all strains after administration of IIV4.
Vaccine efficacy against moderate to severe influenza was 63%, whereas efficacy against influenza of any intensity was 50%. In addition, immunogenicity and efficacy were higher in the 18- to 35-month age group than in the 6- to 17-month age group.
IIV4 also reduced the influenza effect on healthcare use and daily activities by half. Influenza-related emergency department visits were reduced by 79%. No significant differences in safety outcomes between IIV4 and control vaccine were found.
The study authors concluded that their study “adds to the body of existing evidence to support universal vaccination of all children from 6 months of age, irrespective of risk status, to prevent influenza in this age group and to reduce to spread of influenza in the general population.”
Disclosure: This study was funded by GlaxoSmithKline Biologicals SA.
Claeys C, Zaman K, Dbaibo G, et al; for the Flu4VEC Study Group. Prevention of vaccine-matched and mismatched influenza in children aged 6–35 months: a multinational randomised trial across five influenza seasons [published online March 5, 2018]. Lancet Child Adolesc Health. doi: 10.1016/S2352-4642(18)30062-2