Questions and Answers: The NIH 2009 H1N1 Influenza Vaccine Trials in HIV-Infected Children, Youth and Pregnant Women
Why is it important to test the 2009 H1N1 influenza vaccine in HIV-infected children, youth and pregnant women?
It is important to test the 2009 H1N1 influenza vaccine in HIV-infected populations, particularly children, youth and pregnant women, because HIV infection and pregnancy both increase the risk for a poor immune response to the normal 15-microgram dose of seasonal influenza vaccine given to the general population. In addition, children, young people and pregnant women are at higher risk for more severe illness from the 2009 H1N1 influenza virus than other groups, and HIV-infected individuals in these populations may be particularly vulnerable. Because of the increased vulnerability of these populations, these trials are testing whether doses of licensed 2009 H1N1 influenza vaccine that are higher than doses being tested in other groups can safely elicit protective immune responses in HIV-infected children, youth and pregnant women.
Who will participate in these 2009 H1N1 influenza vaccine clinical trials?
One trial will enroll 130 HIV-infected pregnant women ages 18 to 39 years who are in their second or third trimester (14 to 34 weeks) of pregnancy. The other trial will enroll 140 children and youth aged 4 to 24 years who were infected with HIV at birth.
When did the trials begin and when will results become available?
The trial in HIV-infected pregnant women began on October 7, 2009, and the trial in HIV-infected children and youth began on October 14, 2009. Results from both trials will become available during the first quarter of 2010.
Where will the trials take place?
The following 35 sites and eight sub-sites across the United States and Puerto Rico are eligible to participate in the trials:
||The Children's Hospital, University of Colorado Denver
||Johns Hopkins University
University of Maryland
||University of Alabama Birmingham
||Boston Medical Center Pediatric HIV Program
Children's Hospital of Boston
||Children's Memorial Hospital
Rush University Cook County Hospital
||Wayne State University
|District of Columbia:
||Howard University Hospital Department of Pediatrics
Children's National Medical Center
Washington Hospital Center
||Duke University Medical Center Department of Pediatrics
|Fort Lauderdale, Fla.:
||Children's Diagnostic & Treatment Center
||Texas Children's Hospital
||University of Florida Jacksonville
|Long Beach, Calif.:
||Miller Children's Hospital
|Los Angeles, Calif.:
||Children's Hospital of Los Angeles
UCLA Medical Center Department of Pediatrics
University of Southern California Health Sciences Campus
||Regional Medical Center at Memphis
St. Jude Children's Research Hospital
||University of Miami Department of Pediatrics
||University of Medicine & Dentistry of New Jersey
||Bellevue Hospital Center, NYU Medical Center
Bronx/Lebanon Hospital, Department of Pediatrics
Jacobi Medical Center
Metropolitan Hospital Center
Morgan Stanley Children's Hospital of New York-Presbyterian
||The Children's Hospital of Philadelphia
|University of Puerto Rico Maternal Infant Studies Center
||Strong Memorial Hospital, University of Rochester
||UC San Diego Medical Center
||University of California San Francisco
|San Juan City Hospital
||Harborview Medical Center
Seattle Children's Hospital
University of Washington
|Stony Brook, N.Y.:
||SUNY Stony Brook
||University of South Florida
||Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center
||University of Massachusetts Medical School
Who is funding, sponsoring and conducting these 2009 H1N1 influenza vaccine trials?
The International Maternal Pediatric Adolescent AIDS Clinical Trials Group is conducting the studies, which are sponsored and funded by the National Institute of Allergy and Infectious Diseases (NIAID) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, both part of the National Institutes of Health.
NIAID's Division of Microbiology and Infectious Diseases is supporting laboratory analyses for the study of the vaccine in HIV-infected pregnant women.
Who manufactured the 2009 H1N1 influenza vaccine being tested in these trials?
Novartis Vaccines and Diagnostics of Cambridge, Mass., manufactured the 2009 H1N1 influenza vaccine being tested in these clinical trials. This vaccine is licensed by the U.S. Food and Drug Administration.
Is it possible to become infected with the 2009 H1N1 influenza virus by receiving the vaccine in these trials?
No. The vaccine is made from an inactivated form of the 2009 H1N1 influenza virus. It is impossible to become infected with the virus by receiving this vaccine.
Does the vaccine contain an adjuvant or thimerosal?
The vaccine does not contain an adjuvant, a substance that is added to some vaccines to improve the body's immune response to the vaccine.
The 2009 H1N1 influenza vaccine manufactured by Novartis contains a trace amount of thimerosal, a mercury derivative used in the manufacture of the vaccine and removed by subsequent purification steps. The only known side effects of receiving trace amounts of thimerosal in vaccines have been minor reactions such as redness and swelling at the injection site. More information on the use of thimerosal in vaccines can be found on the Web site of the Centers for Disease Control and Prevention (CDC -- Concerns -- Mercury and Vaccines (Thimerosal) -- Vaccine Safety).
What are the study designs?
Both trials are Phase II, multi-site, open-label studies.
Participants will receive two 30-microgram doses of the vaccine 21 days apart. The HIV-infected children and youth will be followed for 7 months, while the HIV-infected pregnant women will be followed from the time they enroll in the study until 6 months after giving birth. Their newborns, who will not receive any vaccinations, will be followed for 6 months after birth.
All participants in the trial of pregnant women must be taking antiretroviral therapy (ART).
In the trial with children and youth, participants will be stratified by age into three groups to better monitor age-related variation in their response to the vaccine.
Group 1: 4 to 9 years of age
Group 2: 10 to 17 years of age
Group 3: 18 to 24 years of age
Participating children and youth do not need to be taking ART, but if they are, they must have been on a stable ART regimen for at least 90 days prior to vaccination with no intention to modify the regimen within the next 60 days following study entry. If the children and youth are not on ART, they should not intend to initiate therapy within the next 60 days following study entry.
If a youth becomes pregnant before receiving the second dose of vaccine, that dose will be deferred until at least her 14th week of pregnancy, and she will be followed until up to 28 days after giving birth.
How is safety being monitored in the trial?
The study team is monitoring the safety of volunteers when they receive their vaccinations and during follow-up visits, and the site investigators and NIH medical officers are monitoring safety on a weekly basis. Also, an independent panel of experts known as a Safety Monitoring Committee is available for ad hoc meetings as needed throughout the trials.
How will the investigators know whether the vaccine has a protective effect against 2009 H1N1 influenza virus in HIV-infected children, youth and pregnant women?
The strength and longevity of the immune response elicited by the vaccine will be gauged in several ways.
The study team will take blood samples from the pregnant women after each dose and 3 and 6 months after delivery to measure the concentration of antibodies the women produce against 2009 H1N1 influenza virus and how strong that antibody response remains over time. After the women give birth, study staff will sample umbilical cord blood to measure the concentration of maternal antibodies against the virus that were transferred to the infants through the placenta. The study team also will collect small blood samples from the infants at 3 and 6 months of age to measure their levels of maternally-derived antibody protection from the virus over time. The infants will not receive the vaccine.
Similarly, in children and young people, the strength and longevity of the immune response will be gauged by testing blood samples taken 21 days after the first dose, 10 days after the second dose, and 6 months after entering the study.
Why aren't these trials testing 15-microgram doses of 2009 H1N1 influenza vaccine like the trials in healthy individuals, and what is the scientific rationale for giving HIV-infected children, youth and pregnant women higher doses of the 2009 H1N1 influenza vaccine than other groups?
Previous studies have shown that HIV infection increases the risk of inadequate immune responses to standard doses of some vaccines. Research on seasonal influenza vaccine and vaccines for other diseases in HIV-infected and other populations suggest that higher doses of vaccine tend to elicit stronger immune responses. These stronger responses, in turn, increase the concentration of protective antibodies in the bloodstream, which is beneficial to both the vaccinated individual and, if pregnant, to her fetus. This is the rationale for testing whether higher doses of licensed 2009 H1N1 influenza vaccine elicit a protective immune response in HIV-infected individuals and whether that protection is transferred to the fetuses of vaccinated pregnant women.
Will the vaccine provide protection to a newborn whose mother was vaccinated during pregnancy?
It is expected that the vaccine will give the infants of vaccinated mothers protection against infection by the 2009 H1N1 influenza virus. This protection likely will result from the transfer of anti-H1N1 influenza antibodies from the vaccinated mother through the placenta to her fetus.
In a study of maternal immunization published in 2008, there was a 63 percent reduction of influenza illness in infants up to 6 months of age whose mothers had received inactivated seasonal influenza vaccine while pregnant. (See K Zaman et al. Effectiveness of maternal influenza immunization in mothers and infants. New England Journal of Medicine DOI:10.1056/NEJMoa0708630 .)
How does the 2009 H1N1 influenza vaccine compare with the seasonal influenza vaccine?
The 2009 H1N1 flu vaccine being tested in this clinical trial is very similar to the annual influenza vaccine recommended by the CDC. The vaccine is produced in the same way as most seasonal flu vaccines: virus is grown in fertilized chicken eggs, then the virus is inactivated and used to make the vaccine. Seasonal inactivated virus influenza vaccines have been used in the United States for decades and have an excellent safety profile.
Where can I get information about other NIAID-sponsored trials of H1N1 influenza vaccine?
For information about other NIAID-sponsored clinical trials of 2009 H1N1 flu vaccines, please see the following sets of questions and answers:
Where can I get additional information about HIV and H1N1 influenza virus?
Additional information about HIV and H1N1 influenza virus is available from the CDC.
Where can I get additional information about influenza and pregnancy?
Information for the general public and for healthcare providers about 2009 H1N1 influenza vaccines in pregnant women is available from the CDC.
Also available is a www.flu.gov Web chat on 2009 H1N1 influenza and pregnant women featuring a panel of experts including NIAID Director Anthony S. Fauci, M.D.
For more information about the NIH-sponsored clinical trials of H1N1 influenza vaccine in HIV-infected pregnant women, children and youth, see NIH Launches 2009 H1N1 Influenza Vaccine Trial in HIV-Infected Pregnant Women: Trial in HIV-Infected Children, Youth to Begin Next Week.