The rationale for quadrivalent influenza vaccines

Abstract

Two antigenically distinct lineages of influenza B viruses have circulated globally since 1985. However, licensed trivalent seasonal influenza vaccines contain antigens from only a single influenza B virus and thus provide limited immunity against circulating influenza B strains of the lineage not present in the vaccine. In recent years, predictions about which B lineage will predominate in an upcoming influenza season have been no better than chance alone, correct in only 5 of the 10 seasons from 2001 to 2011. Consequently, seasonal influenza vaccines could be improved by inclusion of influenza B strains of both lineages. The resulting quadrivalent influenza vaccines would allow influenza vaccination campaigns to respond more effectively to current global influenza epidemiology. Manufacturing capacity for seasonal influenza vaccines has increased sufficiently to supply quadrivalent influenza vaccines, and methods to identify the influenza B strains to include in such vaccines are in place. Multiple manufacturers have initiated clinical studies of quadrivalent influenza vaccines. Data from those studies, taken together with epidemiologic data regarding the burden of disease caused by influenza B infections, will determine the safety, effectiveness, and benefit of utilizing quadrivalent vaccines for the prevention of seasonal influenza disease.

Figure 1. Influenza B circulation as a proportion of circulating influenza strains: US and European data for 2001 to 2011. US data (A) were extracted from cumulative data reported in the final CDC weekly influenza surveillance report for each season (available at www.cdc.gov/flu/weekly/pastreports.htm). Data for 2008–2009 represent cumulative data through April 18, 2009. EU data (B) were extracted from cumulative Euroflu sentinel site data reported in the final weekly influenza surveillance bulletin for each season beginning with the 2003–2004 season (available at www.euroflu.org/cgi-files/bulletin_v2.cgi). Because Euroflu bulletins issued before 2003–2004 do not provide cumulative season data, data presented for the 2001–2002 and 2002–2003 influenza seasons were extracted from the final cumulative European Influenza Surveillance Scheme report issued in 2007 (available at www.euroflu.org/documents/eiss_annual_report_2006-2007.pdf).

Figure 2. Proportion of US pediatric influenza deaths by viral type (2004 to 2011, excluding 2009–2010 pandemic). Values in columns represent the number of deaths in each category for each season. Data for the 2004–2005 through 2008–2009 seasons were obtained via personal communication with the CDC. Pediatric influenza deaths became reportable in 2004–2005; as a result, comparable data are not available prior to 2004–2005. Data for the 2010–2011 season was obtained from the CDC 2010–2011 Influenza Season Summary (available at www.cdc.gov/flu/weekly/pastreports.htm).

Figure 3. Evolution of two antigenically distinct lineages of influenza B (1970–2006). Phylogenetic tree of the influenza B virus HA1 domain based on 214 sequences sampled annually between 1970 and 2006. Data for the B/Victoria/02/87-like and B/Yamagata/16/88-like lineages are shown. Representative vaccine strains are also shown. Adapted with permission from Chen R. Holmes E.C. The evolutionary dynamics of human influenza B virus.

Figure 4. Influenza B circulation by lineage: US and European data for 2001 to 2011. Data were obtained as reported for Figure 1. US data are represented in panel A (A) and European data are represented in panel B (B). The influenza B lineage (Victoria or Yamagata) recommended for inclusion in the trivalent vaccine is shown on the x-axis for each season. EU data regarding the proportion of B viruses by lineage were not available for the 2001–2002 and 2002–2003 influenza seasons.