Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Influenza H1N1 vaccine
Panvax H1N1 vaccine (CSL)
single dose vials containing 15 microgram of haemagglutinin in 0.5 mL and multi dose vials containing 5 mL or 10 mL vaccine
Approved indication: prevention of 2009 H1N1 influenza
Australian Medicines Handbook section 20.1
Following the rapid spread of a new influenza A H1N1 virus, also called swine flu, the World Health Organization (WHO) declared an influenza pandemic on 11 June 2009.1 This prompted the development of a 2009 H1N1 vaccine.
Using the same methods employed to make the seasonal influenza vaccine2, a monovalent split-virus inactivated vaccine that does not have adjuvant has been developed. The virus, which was grown in embryonated chicken eggs, was prepared from the reassortant vaccine virus NYMC X-179A derived from the influenza A/California/7/2009 H1N1 virus (recommended by the WHO).
The safety and immunogenicity of two doses of the vaccine 15 microgram of haemagglutinin antigen in 0.25 mL and 30 microgram in 0.5 mL have been tested in 240 healthy adults (aged 18-64 years) in South Australia.3 Half of the participants were aged 50 or over. Pregnant women were not included in the trial. Two injections of the vaccine were given three weeks apart, in the deltoid muscle of the upper arm. An interim analysis of patient sera found that most people in the trial had produced a robust antibody response three weeks after receiving the first dose (15 or 30 microgram). Neutralising antibody titres of 1:40 or more in a haemagglutination-inhibition assay were observed in 96.7% of people in the lower dose group and 93.3% in the higher dose group. (The haemagglutination-inhibition assay quantifies the highest dilution of patient sera that is able to block haemagglutination of red blood cells by H1N1 virus.) On average, 74.2% (66.1-82.3%) of participants had either seroconverted or had a significant increase in antibody titre. However, people aged 50 or over had a lower-fold increase in antibody response from baseline compared to younger participants.3
The fact that most people had high antibody titres after one vaccination was an unexpected result - it was anticipated that two doses of the vaccine would be needed as most people would not have had previous exposure to the H1N1 virus. However, at baseline it turned out that over a third of participants (76 of 240) already had antibody titres of 1:40 or more in the haemagglutination-inhibition assay, regardless of their age. This proportion was even higher in people who had received the 2009 seasonal influenza vaccine 44% of them (48 of 108) had antibody titres of 1:40 or more at baseline.
The most commonly reported adverse events in the trial were tenderness (30.8% of vaccinees), pain (20.8%) and induration (10%) at the injection site. Other common events included headache (25.8%), malaise (11.7%) and myalgia (15.8%). Three people reported influenza-like illness one of these tested positive for 2009 H1N1 influenza eight days after vaccination while the other two people tested negative. There were no withdrawals from the trial.3
The vaccine is indicated for adults, adolescents and children over 10 years of age and should be given by intramuscular or deep subcutaneous injection. However, it should not be given to people who have had a life-threatening reaction to influenza vaccination, or who have had Guillain-Barr syndrome within six weeks of a previous influenza vaccination. Likewise, it is contraindicated in people who have anaphylactic hypersensitivity to eggs, chicken protein or other constituents of the vaccine. Immune responses to the vaccine may be lower in immunocompromised patients. Immunisation should be postponed in people who have a febrile illness or acute infection.
Based on the interim analysis, it appears that a single 15 microgram dose of the vaccine is immunogenic in healthy adults. However, around a third of people in the trial already had H1N1-specific antibodies before they were vaccinated.3 The actual effectiveness of the vaccine to protect against influenza A H1N1 virus will not be known until after a mass immunisation program has taken place. Vulnerable groups of patients such as pregnant women, children, the elderly and people with impaired immunity were not included in the trial so it is not known how the vaccine will perform in these individuals.
manufacturer provided additional useful information
Notes on references
At the time the comment was prepared, information about this drug was available on the web site of the Food and Drug Administration in the USA (www.fda.gov).
At the time the comment was prepared, a scientific discussion about this drug was available on the website of the European Medicines Agency (www.emea.europa.eu).
- World Health Organization. Director-General statement following the meeting of the Emergency Committee. 2009 Jun 11. www.who.int/csr/disease/swineflu/4th_meeting_ihr/en/index.html[cited 2009 Sep 29]
- Talbot HK, Keitel W, Cate TR, Treanor J, Campbell J, Brady RC, et al. Immunogenicity, safety and consistency of new trivalent inactivated influenza vaccine. Vaccine 2008;26:4057-61.
- Greenberg ME, Lai MH, Hartel GF, Wichems CH, Gittleson C, Bennet J, et al. Response after one dose of a monovalent influenza A (H1N2) 2009 vaccine - preliminary report. N Engl J Med 2009;361:1-10.