Concomitant administration of seasonal trivalent and pandemic monovalent H1N1 live attenuated influenza vaccines

To the editor: In the United States, live attenuated influenza vaccine (LAIV) will play a prominent role in the novel A(H1N1) pandemic vaccination campaign; more than 40 million doses have been purchased by the US Government. Additionally, approximately 10 million doses of seasonal trivalent LAIV will be available for use during the 2009–2010 influenza season. Seasonal trivalent LAIV is currently approved for use in eligible individuals aged 2–49 years in the United States, South Korea and Hong Kong. Because some US populations have been recommended to receive both seasonal trivalent and pandemic monovalent vaccine during the 2009–2010 influenza season, questions have arisen regarding concomitant vaccination with seasonal trivalent and pandemic monovalent LAIV. Historically, recommendations of the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices (ACIP) have stated, ‘In the absence of specific data indicating interference, following ACIP’s general recommendations for vaccination is prudent. Inactivated vaccines do not interfere with the immune response to other inactivated vaccines or to live vaccines. Inactivated or live vaccines can be administered simultaneously with LAIV. However, after administration of a live vaccine, at least 4 weeks should pass before another live vaccine is administered’. Specific guidance was published in 2009 related to vaccination with pandemic monovalent vaccines, which stated, ‘Simultaneous administration of inactivated vaccines against seasonal and novel influenza A (H1N1) viruses is permissible if different anatomic sites are used. However, simultaneous administration of LAIV against seasonal and novel influenza A (H1N1) virus is not recommended’. It was subsequently noted that the recommendation against simultaneous intranasal administration of seasonal and pandemic LAIV was because of theoretical concerns for potential interference between the vaccines. Here, we report the results of a study designed to examine the potential for interference following concomitant administration of seasonal and pandemic LAIV in ferrets, a widely accepted and relevant animal model often used to examine influenza virus and influenza vaccine immunogenicity, including annual World Health Organization and US Food and Drug Administration evaluation of candidate vaccine strains. Twenty 8-week-old male ferrets (Triple F Farms, Sayre, PA, USA) seronegative for all four influenza strains were used in the study. One cohort (n = 4) was inoculated intranasally with a 0Æ2-ml dose (0Æ1 ml per nostril) of seasonal trivalent LAIV containing 10 fluorescent focus units (FFU) of each of the three cold-adapted, temperature-sensitive vaccine strains recommended for inclusion in the 2009–2010 vaccine: A ⁄ South Dakota ⁄ 6 ⁄ 2007 (H1N1) (A ⁄Brisbane ⁄ 59 ⁄ 2007-like), A ⁄Uruguay ⁄ 716 ⁄ 2007 (H3N2) (A ⁄Brisbane ⁄ 10 ⁄ 2007-like) and B ⁄Brisbane ⁄ 60 ⁄ 2008. A second cohort (n = 4) was inoculated intranasally with 10 FFU per dose of the cold-adapted, temperaturesensitive 2009 H1N1 monovalent vaccine, A ⁄California ⁄ 07 ⁄ 2009 (H1N1). A third group (n = 12) was inoculated intranasally with pandemic monovalent LAIV followed by seasonal trivalent LAIV approximately 15 seconds later. This third cohort included more animals to allow for further division into three subgroups to investigate second-dose responses if interference was observed. Sera were collected weekly, and the immunogenicity and kinetics of the immune response were determined by strain-specific serum hemagglutination inhibition (HAI) on days 0 (pre-dose), 14 and 28 post-inoculation using standard methods with 0Æ5% chicken erythrocytes. Coldadapted virus antigen was used for A ⁄California ⁄ 07 ⁄ 2009; wild-type antigen was used for seasonal strains. DOI:10.1111/j.1750-2659.2009.00109.x www.blackwellpublishing.com/influenza Letter to the Editor