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October 8, 2009

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QUESTIONS AND ANSWERS
NIAID Trials of 2009 H1N1 Influenza Vaccines Plus Adjuvant


1. What is an adjuvant?

An adjuvant is a substance added to a vaccine to enhance the immune response to the vaccine.  The main reasons adjuvants are paired with vaccines are 1) to boost the immune response in certain age groups or in people with underlying health conditions who can not mount an adequate immune response to a vaccine made without adjuvant; 2) to broaden the immune response to a vaccine to provide better protection against a virus if it mutates; and 3) to stretch the vaccine supply if it is limited.

2. Who is sponsoring these trials of 2009 H1N1 influenza vaccines plus adjuvant?

These trials of 2009 H1N1 influenza vaccines plus adjuvant are sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, in collaboration with the Biomedical Advanced Research and Development Authority of the Department of Health and Human Services. NIAID is conducting these trials through its longstanding vaccine clinical trials infrastructure known as the Vaccine and Treatment Evaluation Units.

3. The vaccines being distributed in the U.S. immunization program against 2009 H1N1 influenza do not contain an adjuvant. Why is it important to conduct clinical trials of  these vaccines with an adjuvant?

Early results from ongoing clinical trials conducted independently by NIAID and by vaccine manufacturers indicate that one 15-microgram dose of 2009 H1N1 influenza vaccine without adjuvant will be enough to protect most healthy adults and older children from the virus. Thus, the United States does not plan to use adjuvants in the 2009 H1N1 influenza immunization program.

NIAID is conducting clinical trials of adjuvanted vaccine, however, as a contingency plan in case adjuvants are needed in the future against the 2009 H1N1 influenza virus or other influenza viruses with pandemic potential. Influenza viruses are unpredictable and can mutate as they circulate in animal and human hosts. An adjuvanted vaccine may be required if an influenza virus mutates so it becomes less well-matched to the vaccine; if certain populations do not mount a strong enough immune response to unadjuvanted vaccine; or if the supply of vaccine becomes limited and inadequate to protect the public.

4. What is the adjuvant being used in this trial?

The adjuvant being used in this trial, AS03, is made by GlaxoSmithKline (GSK). AS03 is an oil-in-water emulsion-based adjuvant. Emulsion-based adjuvants have been approved for use in some seasonal and pandemic flu vaccines licensed in Europe.

5. What is known about the safety of the adjuvant being used in this trial?

GSK reports that AS03-adjuvanted vaccines have been tested in clinical trials involving more than 39,000 people and have generally been well tolerated.  GSK’s pre-pandemic and pandemic avian flu vaccines, both of which contain AS03, have received regulatory approvals in both the European Union and some Asian countries.

6. Are there any U.S.-licensed vaccines containing adjuvants?

In the United States, adjuvants made from aluminum salts, called alum, are the only ones approved for use in human vaccines licensed by the Food and Drug Administration. Previous NIAID-sponsored  trials of influenza vaccines containing alum found that this particular adjuvant did not substantially increase the immune response to the influenza vaccine.

Other newer adjuvants, including AS03, have been shown to work better than alum in boosting the immune response to influenza vaccines, and some of these adjuvants have received regulatory approval for use in seasonal and pandemic flu vaccines in the European Union. These and other new adjuvants are likely to play an important role in the continued development of seasonal and pandemic influenza vaccines worldwide.

7. Who is eligible for the trial?

The trial will enroll up to 750 healthy adults: about 500 volunteers will be 18 to 64 years old, and the remainder, approximately 250 participants, age 65 years or older.

8. What is the design of the trial?

Participants will be divided into five groups based on the amount of vaccine they receive and whether or not it is paired with the AS03 adjuvant. The five groups are 3.75, 7.5, or 15 micrograms of vaccine plus adjuvant; and 7.5 or 15 micrograms of vaccine without adjuvant. Each volunteer will receive two doses of the vaccine with or without the adjuvant approximately 21 days apart. Neither the volunteers nor the study researchers will know who receives which vaccine preparation.

Study investigators will gather information about the safety of the adjuvanted vaccine and also will look for indicators of immune responses (such as the production of antibodies against 2009 H1N1 influenza virus). Blood samples will be drawn at set time points before and after the first and second injections to provide information about the immune response to the vaccine.

9. When did the trial start?

On September 24, 2009, the first volunteer received adjuvanted 2009 H1N1 influenza vaccine as part of the study.

10. Where can people enroll in the study?

The study is being conducted at seven sites, including five NIAID Vaccine and Treatment Evaluation Units (VTEUs), a network of clinical trial sites at medical research institutions nationwide. The five participating VTEUs include

  • Seattle Group Health Research Institute, the lead site
  • Emory University, Atlanta
  • University of Iowa, Iowa City
  • Cincinnati Children’s Hospital Medical Center
  • University of Maryland, Baltimore

The two other sites participating in the trial are

  • Stanford University School of Medicine, Stanford, Calif.
  • University of Washington, Seattle
11. Is there a detailed description of the study available?

A detailed description of this study can be found on the ClinicalTrials.gov Web site.

Sanofi H1N1 Influenza Vaccine With and Without AS03 Adjuvant

12. Is it possible to become infected with 2009 H1N1 influenza virus by receiving this vaccine?

No. The trial is testing a 2009 H1N1 flu vaccine produced by Sanofi Pasteur in their U.S. vaccine facility in Swiftwater, PA. The vaccine is made from an inactivated form of 2009 H1N1 influenza virus. It is impossible to become infected with the virus from this vaccine.

13. Does the candidate vaccine contain the preservative thimerosal?

Yes, the 2009 H1N1 vaccine used in this study contains the preservative thimerosal to prevent potential contamination after the vaccine vial is opened. The only known side effects of receiving low doses of thimerosal in vaccines have been minor reactions such as redness and swelling at the injection site. For more information on the safety of thimerosal, see information on the NIAID Web site, on the CDC Web site, and on the Food and Drug Administration Web site.

14. How does the 2009 H1N1 influenza vaccine compare with the seasonal influenza vaccine?

The 2009 H1N1 flu vaccine being tested in this clinical trial was made in the same way as the seasonal influenza vaccine and was produced by Sanofi Pasteur in their U.S. vaccine facility in Swiftwater, PA. The virus is first grown in fertilized chicken eggs and then inactivated and used to make the vaccine. Seasonal inactivated virus influenza vaccines have been used in the United States for more than 50 years and have an excellent safety record.

15. How is safety being monitored in the trial?

Safety is being closely monitored throughout the trial, both by the study investigators and by an independent panel of experts known as a Safety Monitoring Committee. This committee was convened by NIAID to review the data from this and other NIAID-sponsored 2009 H1N1 influenza vaccine trials. The committee reviews safety data to look for patterns in the data that would affect the well-being of people in the trial. The committee has the authority to make recommendations to alter or modify or stop trials based on the safety data.

16. How long will the trial last?
Trial participants will be involved in study-related procedures for up to 13 months.  Investigators will monitor the health of the participants throughout this period.
17. When will results from this trial of adjuvanted vaccine become available?
Preliminary information on the immune response following the first dose of vaccine given with or without adjuvant is expected in late October or early November.
18. Does NIAID plan any additional trials of adjuvanted 2009 H1N1 influenza vaccines?
Yes, NIAID is planning another trial of the same design using AS03 adjuvant paired with 2009 H1N1 influenza vaccine made by a different manufacturer.
19. Where can I get additional information about adjuvants?

General information about vaccine adjuvants is available on the CDC Web site; on the Web site of the CDC-funded Immunization Action Coalition; and on the Web site of the World Health Organization.

20. Where can I get additional information on other NIAID-sponsored trials of candidate 2009 H1N1 influenza vaccines?

Where can I get additional information on other NIAID-sponsored trials of candidate 2009 H1N1 influenza vaccines?

For more information about other NIAID-sponsored clinical trials of candidate 2009 H1N1 flu vaccines, see the following Questions and Answers documents:

Media inquiries can be directed to the NIAID Office of Communications at 301-402-1663, niaidnews@niaid.nih.gov.


NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at www.niaid.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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Last Updated October 07, 2009