Overview of Novartis’ H5N1 Influenza Vaccine, surface antigen, adjuvanted with MF59®

Theodore F. Tsai

Title of Contribution: Overview of Novartis’ H5N1 Influenza Vaccine, surface antigen, adjuvanted with MF59®
Author(s):  Theodore F Tsai MD MPH FIDSA   theodore.tsai@novartis.com
Affiliation(s):Novartis Vaccines, Cambridge, MA 02139 USA 

Abstract:
Recurrent avian outbreaks and sporadic human cases of A/H5N1 influenza infection underscore the virus’ potential to spread in more widespread epidemics and, potentially, in a pandemic.  Prepandemic H5N1 vaccination could facilitate public health preparedness to H5N1 outbreaks by providing a measure of protection to the primed population and by allowing for an emergency response that necessitated only a single dose of the pandemic vaccine to rapidly elicit protective immunity.   Novartis’ adjuvanted candidate subunit H5N1 vaccine, AFLUNOV®, currently is formulated with 7.5 µg of a A/Vietnam/1194/2004 strain hemagglutinin (HA) and is adjuvanted with MF59, an oil-in-water emulsion.  Primary vaccination  is with two doses separated by 28 days.  Similar MF-59 adjuvanted formulations containing a H5N1 clade 2.2 antigen, H9N2 or H5N3 HA antigens also have been studied.

The vaccine has exhibited critical features needed in a prepandemic vaccine including

1.  good tolerability and absence of major safety signals in 10 clinical trials, including 5101 subjects, 3 to >85 years of age;
   
2.  no confirmed safety signals in an auxiliary database numbering >33,000 subjects who received the MF59 adjuvant in a variety of investigational and licensed vaccines, in subjects ranging in age from 5 months to 100 years old;  
3. the absence of major safety signals in passive surveillance of 27 million recipients of a licensed seasonal influenza vaccine, also adjuvanted with MF59;
   
4. hemagglutination inhibition (HI), microneutralization (MNT), or single radial hemolysis (SRH) antibody responses to primary vaccination exceeding CHMP criteria for the homologous antigen in subjects from 6 months and older but, also, for a clade 2.2 A/turkey/Turkey/1/2005 antigen in young and older adult subjects;
5.  yet more broadly reacting pseudotype neutralizing antibodies against clade 2.1 (A/Indonesia/5/2005) and clade 2.3.4 (A/Anhui/1/2005) strains;
6.  the rapid induction of memory T cells within 7 days after the first dose and the rapid expansion of this cell population on booster immunization 6 months later;
7.  stimulation of rapid anamestic seroprotective antibody responses, within 7 days after administration of a booster dose in subjects who had been primed 6-8 years earlier with an MF59 vaccine containing an antigenically distinct clade 0-like H5N3 virus - these HI antibodies exceeding a 1:40 titer against representative viruses in clades 0, 1, 1v,  2.1, 2.2, and 2.3.4.

These properties of the MF59-adjuvanted H5N1 vaccine indicate its potential utility in priming populations, especially for persons essential to maintain societal functions during a pandemic.