Five months after the first reported US case of H1N1 influenza, and 4 months after the declaration of a Phase 6 Pandemic by WHO, FDA has approved four Influenza A (H1N1) 2009 monovalent vaccines. Three of the vaccines, manufactured by CSL, Novartis, and Sanofi Pasteur, are injectible inactivated vaccines containing 15 mcg of antigen in a 0.5ml dose. They are approved for use as a single intramuscular injection, except in children 4-9 years old (Novartis), and 3-9 years old (Sanofi Pasteur), who require two 0.5 ml intramuscular injections approximately 1 month apart.
Children 6-35 months old require two 0.25 ml doses of the Sanofi vaccine approximately 1 month apart. Sanofi has gone as far as to produce the vaccine in four different presentations, one of which, the prefilled 0.25ml syringe for 6-36 month olds, is distinguished by a pink plunger rod. The CSL vaccine is not approved for people under 18 years of age.
The fourth approved vaccine, manufactured by MedImmune, is an intranasal live attenuated virus vaccine containing 10 million FFUs in a single 0.2 ml dose. A single intranasal dose is recommended for children, adolescents, and adults 10 to 49 years old. As with the inactivated virus vaccines, children 2-9 years old require two doses approximately 1 month apart. The MedImmune vaccine is discussed in detail in the August 10th blog posting.
Clinical results that supported the single 15 mcg dose were finally generated by the NIAID’s Vaccine and Treatment Evaluation Units (VTEUs) at the same time as companies began to publish their independently sponsored clinical trial results. NIAID Director Anthony Fauci reported that, after 8-10 days, a single dose of 15 mcg of the Sanofi Pasteur vaccine generated a robust immune response in 96% of adults aged 18 to 64 and in 56% of adults aged 65 and older. Similarly, among healthy adults who received a single 15 mcg dose of the CSL Limited vaccine, a robust immune response was measured in 80% of adults aged 18 to 64 and in 60% of adults aged 65 and older. CSL independently reported similar results from a trial they sponsored in Australia.
The government has ordered 195 million doses of the vaccine, of which about 45 million doses are expected to be available in mid-October. Of those 45 million doses, it looks like the first available H1N1 vaccine will be MedImmune’s inhaled product. Approximately 3.4 million doses of the inhalable MedImmune vaccine will be shipped and available in the first week of October.
The somewhat surprising (yet replicable) outcome that a single 15 mcg dose of the H1N1 vaccine produces a robust immune response in healthy adults ends a lot of speculation on how many doses will be available for the 2009-2010 flu season. As discussed many times on this blog, the need to go to a higher dose or two shots would have dramatically reduced the already tight vaccine supply; the single 15 mcg dose allows the supply to be stretched further. Only addition of an adjuvant could further stretch the vaccine supply.
Results from a clinical trial sponsored in Germany by GSK show that a single injection of a 5.25 mcg dose combined with their ASO3 adjuvant gave a robust immune response 12 days after immunization in 98% of the healthy volunteers aged 18 to 60 years old. Given the limited global production capacity for the H1N1 vaccine, approval of an adjuvanted H1N1 vaccine, which is likely to occur in Europe, could further boost the global vaccine supply.
