The 2009 H1N1 Influenza Virus Vaccine

Introduction

There are a lot of questions about the vaccine for 2009 H1N1 influenza virus (i.e., novel H1N1 flu, swine flu). Some clinical trials are wrapping up, and data on efficacy and safety of the vaccine are becoming available. In fact, the first vaccines for 2009 H1N1 flu, marketed by CSL, MedImmune, Novartis, and Sanofi Pasteur, were just approved by FDA on September 15, 2009.1 This document reviews information on the H1N1 flu vaccine.

Evidence for Safety and Efficacy

One study of the 2009 H1N1 flu virus vaccine looked at the response to single doses of a monovalent inactivated virus vaccine in healthy persons between the ages of 18 and 64 years of age (n=240). The study was conducted in Australia.2

Subjects got either one 15 mcg dose of the vaccine, or one 30 mcg dose of the vaccine. The vaccine was administered intramuscularly.2

A primary endpoint of the study was achievement of adequate antibody titers. At 21 days after vaccination, around 97% of subjects who received the 15 mcg dose achieved adequate antibody titers, and about 93% of subjects who received the 30 mcg dose achieved adequate antibody titers.2 This outcome confirming the efficacy of a single dose of vaccine was important. Prior to this, it was anticipated that two doses of the vaccine would actually be required.

There were no reports of serious adverse events. Almost half of patients reported a local adverse event, like injection site tenderness or pain. In addition, almost half of subjects reported a systemic adverse event, like headache, malaise, or myalgia. About two-thirds of systemic adverse events were considered related to the vaccine.2

Preliminary data from the U.S. NIH studies which included almost 3,000 subjects appear to similarly support the efficacy of a single 15 mcg dose of the 2009 H1N1 flu vaccine in adults.12

Another study looked at response to adjuvanted vs. nonadjuvanted 2009 H1N1 flu vaccine in adult subjects (n=100). (The addition of an adjuvant to a vaccine can enhance immunogenicity, allowing for smaller doses to be given and increasing the number of persons who can be immunized.) Preliminary data from this study suggest that the immunogenicity imparted by one vs. two 7.5 mcg doses (second dose given on day seven or 14) of the adjuvanted vaccine is similar at day 21. Data on comparisons with the nonadjuvanted vaccine are yet to be published.3 However, adjuvanted vaccines for 2009 H1N1 flu are not expected to be available in the near future.1,4

A trial of 2009 H1N1 flu vaccine was launched in pregnant women in early September 2009. Pregnant women are at a high risk for severe illness with H1N1 flu. Subjects will get either 15 mcg or 30 mcg of the inactivated vaccine manufactured by Sanofi Pasteur. This data, and data on the use of the vaccine in children (trials were approved to begin in August 2009) will be forthcoming. One of the trials in children is looking at the efficacy and safety of the 2009 H1N1 flu vaccine. (In fact, preliminary results show there's good efficacy with one 15 mcg dose of the vaccine for children ten and older.)13 The other is looking at the safety and efficacy of administration of the 2009 H1N1 flu vaccine in relation to the seasonal flu vaccine.5

Miscellaneous Q&A on 2009 H1N1 vaccine

When will the vaccine be available? Vaccines for 2009 H1N1 flu are expected to be available around mid-October 2009.1 Register with your state or local health department to get it. A listing of state contacts is available at http://www.cdc.gov/h1n1flu/vaccination/statecontacts.htm.

Will the vaccines contain adjuvants? People are asking if the vaccines contain adjuvants, like squalene. The answer is "no." All four companies who are manufacturing the 2009 H1N1 flu vaccine have a history of making safe seasonal flu vaccines. The 2009 H1N1 flu vaccines are manufactured using the same process, which does not include the use of adjuvants.1,15

Keep in mind that an adjuvanted vaccine might be considered an option if, at some point in time, the vaccine supply needs to be stretched to cover more people. This isn't expected for the upcoming season.4

As a side note, the World Health Organization (WHO) has looked at the safety of squalene as a vaccine adjuvant. Millions of people have received vaccines that contain squalene. Based on the absence of reports of significant vaccine-related adverse events, WHO has determined that it's safe.14

Will the vaccines contain the preservative thimerosal? Some formulations do contain thimerosal (i.e., Novartis products and the CSL and Sanofi Pasteur multi-dose vials) and some don't (i.e., Sanofi Pasteur single dose products and MedImmune nasal live virus formulation).6-9

Are the vaccines safe and efficacious in pregnant women and children? Experience with seasonal flu vaccine suggests that the immune response in older children, pregnant women, and immunocompetent adults with chronic conditions is similar to that of healthy nonpregnant adults. However, the immune response in children is unclear. Younger children usually have an inferior response to vaccines compared to healthy adults. At this point, children younger than ten years of age should get two doses of the 2009 H1N1 flu vaccine (inactivated or live/intranasal), separated by approximately one month.4,6-9 Individuals ten years and older should only get one dose.4,6-9

Keep in mind that the 2009 H1N1 flu vaccine made by CSL is only approved for adults (i.e., people 18 years and older). The Novartis product is for those who are four years of age and older. The MedImmune product can be used in children as young as two years and in adults as old as 49 years. And the Sanofi Pasteur product can be used in children as young as six months.6-9

The live nasal vaccine made by MedImmune is not approved for use in pregnant women. Only injectable inactivated vaccine should be used in pregnant women.6-9

Will the supply of 2009 H1N1 flu vaccine be adequate? A shortage of the vaccine is not expected, although the vaccine is likely to be available in limited quantities initially.10

Since seasonal flu vaccine is recommended to be given as early as possible, will the effects of a single dose of seasonal flu vaccine last all the way through flu season? Despite the recommendation for early administration of seasonal flu vaccine, CDC does not indicate that a second dose of seasonal flu vaccine should be given to prolong its effect. (Of course children <9 years old who are receiving seasonal flu vaccine [inactivated or live/intranasal] for the first time should get two doses, separated by at least four weeks).11

Conclusion

The first vaccines for 2009 H1N1 influenza are expected to be available by around mid-October 2009. There are currently four manufacturers of the products. Two doses of the H1N1 vaccine are recommended for children younger than ten years of age. A single dose is recommended for those who are ten years and older. The U.S. Department of Health and Human Services Centers for Disease Control and Prevention has more answers to frequently asked questions on 2009 H1N1 flu vaccine available at http://www.cdc.gov/h1n1flu/vaccination/vaccine_safety_qa.htm.

For parents who express concerns about vaccinating their children, pass along our handout "Common Concerns About Childhood Vaccinations" to help them make informed decisions.

Project Leader in preparation of this Detail-Document: Stacy A. Hester, R.Ph., BCPS, Assistant Editor

References

  1. U.S. Food and Drug Administration. FDA approves vaccines for 2009 H1N1 influenza virus. September 15, 2009. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm182399.htm. (Accessed September 17, 2009).
  2. Greenberg ME, Lai MH, Hartel GF, et al. Response after one dose of a monovalent influenza A (H1N1) 2009 vaccine-preliminary report. N Engl J Med 2009;DOI:10.1056/NEJMoa0907413.
  3. Clark TW, Pareek M, Hoschler K, et al. Trial of influenza A (H1N1) 2009 monovalent MF59-adjuvanted vaccine-preliminary report. N Engl J Med 2009;DOI:10.1056/NEJMoa0907650.
  4. Neuzil KM. Pandemic influenza vaccine policy-considering the early evidence. N Engl J Med 2009;DOI:10.1056/NEJMe0908224.
  5. National Institute of Allergy and Infectious Diseases. Questions and Answers. August 19, 2009. http://www3.niaid.nih.gov/news/QA/qaH1N1pedvax.htm. (Accessed September 17, 2009).
  6. Product information for Influenza A (H1N1) 2009 monovalent vaccine. Novartis. Cambridge, MA 02139. September 2009.
  7. Product information for Influenza A (H1N1) 2009 monovalent vaccine. CSL. King of Prussia, PA 19406. September 2009.
  8. Product information for Influenza A (H1N1) 2009 monovalent vaccine. Sanofi Pasteur. Swiftwater, PA 18370. September 2009.
  9. Product information for Influenza A (H1N1) monovalent vaccine live, intranasal. MedImmune. Gaithersburg, MD 20878. September 2009.
  10. Anon. Vaccination. http://pandemicflu.gov/individualfamily/vaccination/index.html. Flu.gov. (Accessed September 17, 2009).
  11. U.S. Department of Health and Human Services Centers for Disease Control and Prevention. Timing of vaccination. http://www.cdc.gov/flu/professionals/acip/timing.htm. (Accessed September 18, 2009).
  12. Fauci A. Early results from clinical trials of 2009 H1N1 influenza vaccines in healthy adults. September 11, 2009. http://www3.niaid.nih.gov/news/newsreleases/2009/H1N1TrialsResults.htm. (Accessed September 21, 2009).
  13. National Institute of Allergy and Infectious Diseases. Early results: in children, 2009 H1N1 influenza vaccine works like seasonal flu vaccine. September 21, 2009. http://www.nih.gov/news/health/sep2009/niaid-21.htm. (Accessed September 22, 2009).
  14. World Health Organization. Squalene-based adjuvants in vaccines. December 2008. http://www.who.int/vaccine_safety/topics/adjuvants/squalene/questions_and_answers/en/index.html. (Accessed September 21, 2009).
  15. CDC. General questions and answers on 2009 H1N1 influenza vaccine safety. September 17, 2009. http://www.cdc.gov/h1n1flu/vaccination/vaccine_safety_qa.htm (Accessed September 28, 2009).

Cite this Detail-Document as follows: The 2009 H1N1 influenza virus vaccine. Pharmacist's Letter/Prescriber's Letter 2009;25(10):251001.

October 2009

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