Novartis influenza A H1N1 vaccine clinical data

influenza-vaccineAlthough the influenza 2009 H1N1 vaccine produced by Novartis, Fluvirin, was previously approved for use in the US, the clinical data supporting its safety and immunogenicity had not been released. The company has now issued a media release containing interim clinical data on the effects of the vaccine in humans.

According to the company, testing of the vaccine in 4,080 adult and elderly (>65 years) US individuals has revealed that a half dose (3.75 micrograms) without adjuvant “fulfilled immune response criteria associated with protection”. I assume that the latter statement means that hemagglutination inhibition titers of 1:40 or greater were observed, but this is not explicitly stated.  Current US guidelines for the 2009 H1N1 2009 vaccine stipulate that adolescents, adults and the elderly should receive one 15 microgram dose, and children 9 years of age and under are required to receive two 15 microgram doses four weeks apart.

Fluvirin with MF59 adjuvant was also tested in children ages 3 to 8, adults ages 18 to 64, and the elderly. The results indicate that a single 3.75 microgram dose of vaccine with adjuvant induced protective levels of immunity. The media release includes the following:

Novartis proprietary MF59 adjuvant has an established safety profile, supported by more than 12 years of clinical safety data and more than 45 million doses of commercial use in Europe. The adjuvant has been studied in clinical trials involving more than 33,000 people, including children, and has been licensed for use in people 65 years of age and over in the seasonal influenza vaccine Fluad® since 1997 in the European Union. Novartis also produces two A(H1N1) vaccines, Focetria® and Celtura®, which contain MF59 and are available outside the US.

MF59 adjuvant contains squalene, polyoxyethylene sorbitan monooleate (Tween 80) and sorbitan trioleate. No vaccine containing this adjuvant has been approved for use in the US.

A media release is no substitute for revealing clinical trial results in a peer-reviewed scientific journal. Novartis indicates that the vaccine trial will be completed in December 2009, and the results should be published shortly thereafter. It’s important for vaccine manufacturers to make clinical trial data freely available to address the concerns of those who are worried about vaccine safety.


twiv-200Hosts: Vincent Racaniello and Jason Rodriguez

On episode #50 of the podcast “This Week in Virology”, Vincent and Jason review influenza 2009 H1N1 vaccine trials and protection against the virus conferred by the 1976 swine flu vaccine, then move on to a virus called XMRV and its possible role in prostate cancer.

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Click the arrow above to play, or right-click to download TWiV #50 (54 MB .mp3, 74 minutes)

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Links for this episode:
One dose of influenza 2009 H1N1 vaccine without adjuvant is enough
Partially completed study on influenza 2009 H1N1 vaccine with MF59 adjuvant
1976 swine flu vaccine induces cross-reactive antibodies against influenza 2009 H1N1 strain
Explanation of hemagglutination-inhibition and microneutralization assays
FDA approves influenza 2009 H1N1 vaccine
XMRV is present in malignant prostatic epithelium and is associated with prostate cancer
Identification of a novel gammaretrovirus in prostate tumors
CDC page on Guillain-Barré syndrome

Weekly Science Picks
Jason Glass Microbiology
Vincent FluWeb Influenza Historical Resources Database

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Adjuvant effect on H1N1 vaccine

There has been a great deal of discussion about the use of adjuvants to improve the immunogenicity of vaccines against the 2009 H1N1 pandemic influenza strain. What effect do these compounds have on the immune response?

Adjuvants are compounds added to vaccines that stimulate the immune response. They are often used when the antigen is in short supply, or does not induce a good antibody response. Because the 2009 H1N1 pandemic influenza strains do not replicate well in eggs, it has been suggested that adjuvants be used to ensure that there is sufficient supply of vaccine.

A recent study demonstrates very clearly the effect of adjuvants on the immune response. Mice were immunized with egg-produced 2009 H1N1 influenza vaccine with or without the adjuvant MF59. A boost inoculation was given on day 21. Sera were taken on days 13 and 21 and the antibody response was measured by hemagglutination-inhibition (HI) assay. If you don’t know how an HI assay works, please read my previous description. The results of the assay are shown in the figure.


One week after immunization with 0.5 micrograms of antigen, the average serum HI titer was 1:15 (bars labeled post1). This titer is barely higher than obtained when mice were immunized with buffer alone (PBS). The HI titer rose to 1:160 after the boost. When MF59 adjuvant was included, the first and second HI titers were significantly higher – 1:63 and 1:1280.

What do thes numbers mean? Protection of humans against seasonal influenza is generally believed to require a HI titer of 1:40 or more. Therefore when MF59 adjuvant is used in mice, one immunization is sufficient to confer protection against disease. Without adjuvant, two doses are required for protection.

Trials are ongoing in adults to determine the immunogenicity of 2009 H1N1 vaccines with and without adjuvant.

I know that many readers are concerned about the possible side effects of adjuvants. MF59 has been used for 12 years in seasonal influenza vaccines in Europe and is considered a safe adjuvant. However, the Centers for Disease Control and Prevention believes that the 2009 H1N1 vaccine will likely not be used with adjuvant.

Dormitzer, PR, Rappuoli, R, Casini, F, Wack, A et al (2009). Adjuvant is necessary for a robust immune response to a single dose of H1N1 pandemic flu vaccine in mice PLoS Currents: Influenza