TWiV 217: I just flu in and my arms are shot

On episode #217 of the science show This Week in Virology, Vincent, Alan, Rich, and Dickson review influenza vaccines.

You can find TWiV #217 at

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.

Influenza A (H1N1) 2009 vaccine: efficacy and safety

influenza-vaccineThere have been many interesting responses to my recent post, “Are you receiving the influenza 2009 H1N1 vaccine?” Some individuals have already been immunized or plan to do so shortly. Others are concerned about the safety and efficacy of the monovalent preparations. As pointed out recently in a Nature editorial, “Mass-vaccination campaigns…must take public concerns into account”, and “officials should focus on providing people with the information they need to make good choices for themselves.” Here are some facts about the influenza H1N1 vaccine for those who haven’t yet made up their minds whether or not to be immunized.

Four companies are licensed to produce the 2009 H1N1 influenza vaccine for the US – CSL Limited, Novartis Vaccines, Sanofi-Pasteur Inc., and MedImmune. The US Food & Drug Administration has published on their website the package insert for each product. These are multipage documents with a good deal of information, including indications, dosage, contraindications, adverse reactions, and the results of clinical studies. Links to the package insert for each vaccine are listed below.

  • CSL Limited – Afluria Influenza A (H1N1) 2009 Monovalent Vaccine (pdf)
  • Novartis Vaccines and Diagnostics – Fluvirin Influenza A (H1N1) 2009 Monovalent Vaccine (pdf)
  • Sanofi Pasteur, Inc – Fluzone Influenza A (H1N1) 2009 Monovalent Vaccine (pdf)
  • MedImmune LLC – Flumist Influenza A (H1N1) 2009 Monovalent Vaccine (pdf)

For example, the package insert for Afluria indicates that the vaccine is supplied as a sterile suspension for intramuscular injection in two forms: a 0.5 mL preservative-free, single-dose, pre-filled syringe; and a 5 mL multi-dose vial containing ten doses. Thimerosal, a mercury derivative, is added as a preservative in the multi-dose vial; each 0.5 mL dose contains 24.5 micrograms of mercury.

The results of two clinical studies on the safety and efficacy of Afluria are also reported: a US study of 1,357 individuals, and a UK study of 275 subjects. No serious adverse effects were reported in either study. The seroconversion rates are included in the form of hemagglutination-inhibition titers.

I encourage everyone to read at least one of these package inserts to become familiar with the extent to which these vaccines have been tested in people. If any aspects of these documents are not clear, don’t hesitate to contact me.

Note added after publication: It was pointed out in the comments that the safety and efficacy data reported in the package inserts were obtained with the seasonal influenza vaccines, Afluria, Fluvirin, Fluzone, and Flumist, not the 2009 monovalent H1N1 vaccine. My apologies for implying otherwise. I will locate the safety and efficacy data for the monovalent H1N1 vaccines and update the post with that information.

Second addendum: According to the FDA, the influenza A (H1N1) 2009 monovalent vaccine has been tested in the same way as new seasonal vaccines that are produced each year. The inactivated influenza A (H1N1) monovalent vaccine manufactured by CSL Limited was tested in 120 adults. By day 21 after vaccination, HI antibody titers of 1:40 or more were observed in 116 (97%) of 120 adults who received a 15 μg dose. Injection site tenderness or pain was reported by 46% of subjects, while 45% of the subjects reported one or more systemic symptoms (headache, malaise, or myalgia). These observations are similar to those observed in testing of seasonal influenza vaccines. The preliminary results have been published.

The Sanofi Pasteur 2009 H1N1 vaccine has been tested in children aged 6-35 months, 3-9 years, and 10-17 years, and the results have been reported by NIAID. After immunization with a single 15 μg dose of vaccine, 25%, 36% and 76% of individuals in each age group developed HI antibody titers of 1:40 or more. No information on adverse effects have been provided.

Medimmune and Novartis have reported immunogenicity and safety study results similar to those observed for seasonal vaccines, but the data have not yet been released.

Although the 2009 H1N1 vaccines produced by all four manufacturers have been approved by the FDA, all the data used for approval have not yet been published or released. As soon as these data are available I will pass them on.