The other severe but non-serious event, asthma, was reported 65 days after the second dose in a 2 year old, and deemed unrelated to study vaccine, with attribution to viral illness

The other severe but non-serious event, asthma, was reported 65 days after the second dose in a 2 year old, and deemed unrelated to study vaccine, with attribution to viral illness. to moderate injection site tenderness, pain and erythema was observed, with the most commonly reported systemic reactogenicity being irritability in children 635 months, and headache and fatigue in children 917 years old. Children 635 months old, whether they received 7.5mcg or 15mcg/dose, had low HAI and Neut antibody responses after two doses compared to older children. Children under 9 years of age required two doses of vaccine to demonstrate a response, while 917 year olds responded well after one dose. Previous influenza vaccination and older age were associated with higher immune responses to H3N2v vaccine. Children 917 years of age also developed cross-reactive antibodies against recent seasonal H3N2 influenza viruses. == Conclusion == The H3N2v vaccine was safe and immunogenic in children and adolescents. Age-related increases in immunogenicity against H3N2v and seasonal H3N2 viruses were observed, suggesting prior priming via infection and/or immunization. Clinical trial registry: The trial is registered withNCT02100436. Keywords:Influenza, H3N2 variant, children, adolescents, safety, immunogenicity, cross-reactive antibodies == Introduction == The recent emergence of novel influenza A viruses in humans, including H1N1pdm09, H5N1, H7N7, H7N9, and H9N2 subtypes, has added urgency to ongoing efforts to prepare for influenza pandemics (1,2,3). From 2011 to 2012, infections with a variant of influenza A/H3N2 that originated in swine (H3N2v) were reported in the United States (410). In contrast to earlier swine-origin H3N2 outbreaks, some patients had no known contact with swine, suggesting limited human-to-human transmission. By late 2013, the Centers for Disease Control and Prevention (CDC) reported a total of 340 confirmed human infections of H3N2v in 13 states, with most infections occurring in children with likely little to no pre-existing immunity (11). Although fewer cases were reported in 2014 and 2015, another outbreak occurred in the summer of 2017 (12). Sustained human-to-human transmission has not occurred (6,11,12). Triple reassortant swine influenza A/H3N2 viruses containing genes from human, swine and avian influenza viruses emerged in swine in 1998 (6). These H3N2v isolates have the matrix gene from the 2009 2009 A/H1N1 pandemic virus (6), with a hemagglutinin (HA) most closely related to H3N2 viruses that circulated in the 1990s. Studies using animal antisera that cross-react with current widely circulating H3N2 influenza strains and viruses used in recent seasonal influenza vaccines exhibit no cross-reactivity with H3N2v. Furthermore, limited serologic studies indicate that young children have little to no pre-existing antibodies to H3N2v, and immunization with seasonal inactivated influenza vaccine (IIV) elicits minimal to no cross-reactive antibodies (1316). Similarly, the prevalence of putatively protective antibody titers against H3N2v before and after seasonal IIV vaccination in adults is low (1316). Influenza vaccines made using current and recently circulating seasonal H3N2 strains are therefore unlikely to significantly protect against H3N2v. After studying a monovalent A/H3N2v vaccine in adults (17), we evaluated its safety and immunogenicity in JNJ-632 children and adolescents. In addition, we evaluated the cross reactivity of vaccine-elicited antibodies to drifted seasonal H3N2 viruses that recently circulated in the US. We hypothesized JNJ-632 that children under 9 years of age would need two doses of monovalent A/H3N2v vaccine to achieve protective antibody concentrations, and that children older than 9 years would respond well to one dose, particularly if previously exposed to similar H3N2 viruses through prior infection or vaccination. == Materials and Methods == == Study Design == We conducted a phase II open label study to assess the safety and immunogenicity of a unadjuvanted subvirion monovalent inactivated influenza A/H3N2v vaccine in healthy children 6 months to 17 years of age, stratified by age group: 635 months, 38 years, and 917 years old. Participants were scheduled to receive 2 doses of H3N2v vaccine administered 21 days apart. Children 635 months were randomized to receive either 7.5mcg or 15mcg of HA/dose. All children 38 years and 917 years old received 15mcg of HA/dose. The study was conducted at 8 National Institutes of Health-funded Vaccine and Treatment Evaluation Units (VTEU) in the US between June 2014 and March 2015. The protocol was approved KSHV K8 alpha antibody by each institutions respective ethics committee and written informed consent and assent were provided by legal guardians and study participants, as appropriate. The trial is registered JNJ-632 withNCT02100436 == Vaccine == The study vaccine was an unadjuvanted monovalent inactivated split influenza virus vaccine produced in eggs using the same manufacturing process for production of the licensed IIV vaccine Fluzone by Sanofi Pasteur, with slight modifications in the formulation step. The H3N2v reassortant for the vaccine (designated A/Minnesota/11/2010 NYMC X-203) was derived from the.