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In February and September each year the World Health Organisation (WHO) recommends influenza viruses to be included in influenza vaccines for the forthcoming winters in the Northern and Southern Hemispheres respectively. These recommendations are based on data collected by National Influenza Centres (NIC) through the Global Influenza Surveillance and Response System (GISRS) and a more detailed analysis of representative and potential antigenically variant influenza viruses from the WHO Collaborating Centres for Influenza (WHO CCs) and Essential Regulatory Laboratories (ERLs). This article provides a detailed summary of the antigenic and genetic properties of viruses and additional background data used by WHO experts during development of the recommendations for the 2012 Southern Hemisphere influenza vaccine composition.

Wild type human influenza viruses do not usually grow well in embryonated hens' eggs, the substrate of choice for the production of inactivated influenza vaccine, and vaccine viruses need to be developed specifically for this purpose. In the event of a pandemic of influenza, vaccine viruses need to be created with utmost speed. At the onset of the current A(H1N1) pandemic in April 2009, a network of laboratories began a race against time to develop suitable candidate vaccine viruses. Two approaches were followed, the classical reassortment approach and the more recent reverse genetics approach. This report describes the development and the characteristics of current pandemic H1N1 candidate vaccine viruses.

Influenza vaccines form an important component of the global response against infections and subsequent illness caused in man by influenza viruses. Twice a year, in February and September, the World Health Organisation through its Global Influenza Surveillance Network (GISN), recommends appropriate influenza viruses to be included in the seasonal influenza vaccine for the upcoming Northern and Southern Hemisphere winters. This recommendation is based on the latest data generated from many sources and the availability of viruses that are suitable for vaccine manufacture. This article gives a summary of the data and background to the recommendations for the 2009-2010 Northern Hemisphere influenza vaccine formulation.

Because of delays in the manufacturing of the 2000-2001, trivalent inactivated influenza vaccine in the US, there were concerns that there might be shortages of vaccine supply in the US, Therefore, we conducted a prospective, randomized, open-label, multicenter trial at six C academic medical centers in the US, to evaluate the immunogenicity of a half dose of inactivated vaccine in healthy adults. Healthy adults between the ages of 18 and 49 were randomized to receive either a full 0.5 ml (15.5 mug of each HA antigen) dose or a 0.25 ml (7.75 mug of each HA antigen) dose of the 2000-2001 trivalent inactivated influenza vaccine by intramuscular injection. Sera were obtained for assessment of hemagglutination-inhibiting antibody to each of the three strains contained in the vaccine before and 21 days after vaccination. The proportions of individuals achieving a post-vaccination titer of greater than or equal to1:40, the geometric mean titers (GMTs) of post-vaccination antibody, and the proportions of individuals with a four-fold or greater increase in antibody were lower for all three strains in those receiving 0.25 ml of vaccine compared to those receiving 0.5 ml. However, the differences were small for all three antigens. The upper 95% confidence limits for differences between 0.25 and 0.5 ml doses were less than 20% for rates of achieving a titer of greater than or equal to1:40 and four-fold response, and less than 1.5 for the ratios of GMTs between dose groups, for all three vaccine antigens. These results suggest that when vaccine is in short supply, a strategy using a half dose in healthy adults could increase the number of people vaccinated with relatively little adverse impact on vaccine immunogenicity. (C) 2002 Published by Elsevier Science Ltd.

Vaccination with the influenza A transmembrane protein M2 provides enhanced viral clearance and recovery from influenza A virus infection in mice. However, the high degree of hydrophobicity of the protein limits its purification for vaccine purposes. We have attempted to alter the structure of the M2 protein to allow high level recombinant expression in Escherichia coli, to reduce its hydrophobicity and improve protein solubility, thus improving its properties as a vaccine subunit candidate. Constructs investigated include deletion of the transmembrane domain of M2 (residues 26-43) and an extended deletion (residues 26-55). A full-length M2 protein was not pursued because of poor expression, even in the presence of amantadine. Expressed as glutathione S-transferase fusion proteins and used to vaccinate mice, either deletion construct was found to raise M2-specific serum antibodies and enhance viral clearance in mice challenged with homologous and heterologous influenza A viruses. Enzymatic cleavage from the GST fusion domain produces soluble protein giving similar results. The results demonstrate that large alterations of M2 protein structure can improve its isolation and purification characteristics without detracting from its immunogenic properties.

Because of the time required to identify and produce an antigenically well-matched pandemic vaccine, vaccines that offer broader cross-reactive immunity and protection are desirable. We have compared a live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) based on a related H5 hemagglutinin (HA) from a nonpathogenic avian influenza virus, A/Duck/Pottsdam/1042-6/86 (H5N2), for the ability to induce cross-reactive immunity and/or cross-protective efficacy against a contemporary highly pathogenic H5N1 viruses. Both LAIV and IIV provided cross-protection from systemic infection, severe disease, and death following lethal challenges with antigenically distinct A/Vietnam/1203/2004 (VN/1203) virus. Substantial levels of serum anti-VN/1203 HA IgG were detected in mice that received either IIV or LAIV, while nasal wash anti-VN/1203 HA IgA was detected in mice that received LAIV. Formulation of IIV with alum adjuvant augmented neutralizing antibody responses and protective efficacy. These results demonstrated that vaccination of mice with H5 IIV or LAIV induced a high degree of cross-protection from illness and death following lethal challenges with a heterologous H5N1 virus.

The immunogenicity and efficacy of Russian live attenuated and US inactivated trivalent influenza vaccines administered alone or in three different combinations were evaluated in a randomized, placebo-controlled, double-blinded study of 614 elderly or chronically ill nursing home residents in St. Petersburg, Russia during the 1996-97 influenza season. Postvaccination serum antibody responses were more frequent among individuals administered the combination vaccines than among those vaccinated with live or inactivated vaccine alone. Only individuals who received live vaccine, alone or in combination with inactivated vaccine, achieved significant postvaccination increases in virus-specific nasal IgA. Efficacy in preventing laboratory-confirmed influenza in vaccinated versus nonvaccinated individuals was 67% (95%CI, 36-81%) for recipients of a combination of the vaccines compared with 51% (95%CI, -17-79%) for recipients of live vaccine alone and 50% (95%CI, -26-80%) for recipients of inactivated vaccine alone. These results suggest that administration of a combination of influenza vaccines may provide a strategy for improved influenza vaccination of elderly people.