NIH Launches 2009 H1N1 Influenza Vaccine Trial in HIV-Infected Pregnant Women

NIH Launches 2009 H1N1 Influenza Vaccine Trial in HIV-Infected Pregnant Women
Trial in HIV-Infected Children, Youth to Begin Next Week

The first clinical trials to test whether the 2009 H1N1 influenza vaccine can safely elicit a protective immune response in pregnant women launched yesterday, and a trial to conduct the same test in HIV-infected children and youth will begin next week. 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 (NICHD), both part of the National Institutes of Health.

“These studies are important 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,” says NIAID Director Anthony S. Fauci, M.D. “Moreover, 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,” adds Lynne Mofenson, M.D., chief of the Pediatric, Adolescent and Maternal AIDS Branch in NICHD.


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.

Thirty-five sites and eight sub-sites across the United States and Puerto Rico are eligible to conduct the trials. Each volunteer will receive two 30-microgram doses of 2009 H1N1 influenza vaccine 21 days apart. (In contrast, the NIAID studies of 2009 H1N1 influenza vaccine in HIV-uninfected children, youth and pregnant women are testing doses of 15 and 30 micrograms.)

Safety data will be collected and monitored closely by the study investigators and an independent safety monitoring committee. 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 three and six 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 H1N1 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 level of maternally derived antibody protection from the virus over time. The infants will not receive 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 six months after entering the study.

The vaccine, manufactured by Novartis Vaccines and Diagnostics, contains inactivated 2009 H1N1 influenza virus, so it is impossible to become infected with the virus by receiving the vaccine. The vaccine does not contain adjuvant, a substance added to some vaccines to improve the body’s response to vaccine.

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 likely 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.

For more information about NIAID-sponsored clinical trials in HIV-infected pregnant women, children and youth, see Questions and Answers (coming soon).

For additional information about NIAID-sponsored clinical trials of candidate H1N1 vaccines: Clinical Trials of 2009 H1N1 Influenza Vaccines Conducted by the NIAID-Supported Vaccine and Treatment Evaluation Units; Pediatric Trials of Candidate 2009 H1N1 Vaccine at NIAID Vaccine and Treatment Evaluation Units (VTEUs); NIAID Trial of 2009 H1N1 Influenza Vaccine in Pregnant Women at the Vaccine and Treatment Evaluation Units.

Visit www.flu.gov for one-stop access to U.S. government information on avian and pandemic influenza and www.aids.gov for comprehensive U.S. government information about HIV/AIDS. A www.flu.gov webcast on H1N1 and pregnant women featuring NIAID Director Dr. Fauci is available. Also, visit NIAID’s Web portals on influenza and HIV/AIDS.


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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 http://www.niaid.nih.gov.

The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute’s Web site at http://www.nichd.nih.gov/.

The National Institutes of Health (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. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.
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QUESTIONS AND ANSWERS
Clinical Trials of 2009 H1N1 Influenza Vaccines
Conducted by the NIAID-Supported
Vaccine and Treatment Evaluation Units


1. When did clinical trials of candidate H1N1 influenza vaccine begin?

NIAID announced the initiation of clinical trials on July 22, 2009.

2. How many trials are there, and what is the purpose of these trials?
The NIAID Vaccine and Treatment Evaluation Units (VTEU) are conducting five clinical trials of two candidate H1N1 influenza vaccines.

The trials are designed to answer three primary questions:

Are these vaccines safe in healthy people of various ages?
How large a vaccine dose, and how many doses of vaccine, are needed to induce an immune response that is predictive of protection?
Can 2009 H1N1 influenza vaccine be safely administered at the same time or sequentially with the seasonal flu vaccine, and will both vaccines induce protective immune responses?

3. What are the Vaccine and Treatment Evaluation Units?

The VTEUs were established by the National Institute of Allergy and Infectious Diseases in 1962. They provide a ready resource for conducting clinical trials that evaluate vaccines and treatments for a wide array of infectious diseases. An important strength of the VTEUs is their ability to rapidly enroll large numbers of volunteers into vaccine trials and to immunize the volunteers in a safe, effective, and efficient manner. This rapid-response capability is especially important for testing vaccines for emerging public health concerns such as 2009 H1N1 influenza.

4. How many VTEUs are there, and where are they located?

There are currently eight VTEUs located at the following sites:

Baylor College of Medicine, Houston
Children’s Hospital Medical Center, Cincinnati
Emory University, Atlanta
Group Health Cooperative, Seattle
Saint Louis University, St. Louis
University of Iowa, Iowa City
University of Maryland School of Medicine, Baltimore
Vanderbilt University, Nashville

5. What trials are being initiated to evaluate candidate 2009 H1N1 influenza vaccines?

The VTEUs are conducting an initial set of five clinical trials of candidate 2009 H1N1 influenza vaccines. Three of these trials are enrolling healthy adult (18 to 64 years old) and elderly (65 years and older) volunteers. After careful review of initial safety data from over 500 adults in the first three trials, two additional trials of similar design began in children in mid-August.

6. How do I find out more information about the VTEU trials?


Detailed information about the trials is available from the NIH www.clinicaltrials.gov Web site. Listed below are the specific links for the initial group of five VTEU trials.

Trial comparing two different strengths (15 microgram versus 30 microgram) and one versus two doses of sanofi pasteur candidate 2009 H1N1 influenza vaccine in healthy adults (18 to 64 years old) and healthy elderly adults (65 years and older). Each of the four groups in this trial will enroll up to 100 volunteers, for a target number of 400 volunteers who will receive the candidate vaccine. An additional 50 volunteers will receive an inactive (placebo) vaccine. For more information, see NCT00943631.
Trial comparing two different strengths (15 microgram versus 30 microgram) and one versus two doses of CSL Limited candidate 2009 H1N1 flu vaccine in healthy adults (18 to 64 years old) and healthy elderly adults (65 years and older). Each of the four groups in this trial will enroll up to 100 volunteers, for a target number of 400 volunteers who will receive the candidate vaccine. An additional 50 volunteers will receive an inactive (placebo) vaccine. For more information, see NCT00943488.
Trial comparing two different strengths (15 microgram and 30 microgram) and one and two doses of sanofi pasteur candidate 2009 H1N1 flu vaccine in healthy children (6 months to 17 years old). Each of the two groups in this trial will enroll up to 300 volunteers, for a target number of 600 volunteers who will receive the candidate vaccine. For more information about this trial, see NCT00944073.
Trial comparing simultaneous and sequential administration of seasonal flu vaccine and sanofi pasteur candidate 2009 H1N1 influenza vaccine in healthy adults (18 to 64 years old) and elderly adults (65 years and older) volunteers. Each of the four groups in this trial will enroll up to 200 volunteers, for a target number of 800 volunteers who will receive the candidate H1N1 vaccine. An additional 50 volunteers will receive an inactive (placebo) vaccine and the seasonal flu vaccine. For more information, see NCT00943878.
Trial comparing simultaneous and sequential administration of seasonal flu vaccine and sanofi pasteur candidate 2009 H1N1 influenza vaccine in primed children (children who have received two doses of seasonal vaccine in one year or are older than 9 years). Each of the four groups in this trial will enroll up to 150 children, for a target number of 600 volunteers who will receive the candidate H1N1 vaccine. For more information, see NCT00943202.

7. Will other sites be participating in these initial five trials?

Some of the VTEUs have sub-sites that will join with the VTEUs in conducting these trials. In addition, to allow for rapid enrollment of volunteers and expand the number of trials, NIAID may fund other sites to help the VTEUs conduct future trials of H1N1 vaccines. Those trials are currently under development.

8. Which VTEU sites are leading the initial set of five trials?

The lead VTEU sites for these trials are the following institutions:

University of Maryland School of Medicine VTEU (Dr. Karen Kotloff, principal investigator) will lead the two trials testing the sanofi pasteur vaccine in healthy adults, elderly, and children.
University of Iowa VTEU (Dr. Pat Winokur, principal investigator) will lead the trials testing the CSL vaccine in healthy adult and elderly volunteers.
Saint Louis University VTEU (Dr. Sharon Frey, principal investigator) will lead the two trials testing the H1N1 vaccines given at the same time as or sequentially with the seasonal flu vaccine in healthy adult and elderly volunteers and in children.
All eight VTEUs are expected to participate in these five trials. The priority for NIAID is to enroll these trials as quickly as possible. In order to optimize quickly enrolling these trials, NIAID wants to maintain maximum flexibility and coverage in assigning specific sites to conduct these trials.

9. Which candidate 2009 H1N1 influenza vaccines are being tested in the VTEU trials, and why were these two vaccines chosen?

This initial set of five VTEU trials is testing two candidate 2009 H1N1 influenza vaccines: one made by sanofi pasteur (Swiftwater, Pennsylvania) and the other by CSL Limited (Melbourne, Australia). These two vaccines were chosen initially for the VTEU trials based on Department of Health and Human Services (HHS) projections of their initial availability and the need to determine as quickly as possible if unadjuvanted vaccines could induce potentially protective immune responses. In addition, seasonal flu vaccine made by sanofi pasteur is licensed in the United States for use in children, which meant that a candidate H1N1 influenza vaccine made by this company can be tested in U.S. children as well. Both vaccines are available in versions made without the preservative thimerosal. Other candidate H1N1 influenza vaccines may be tested in future VTEU trials.

10. How many people will be enrolled in this first set of five VTEU trials?

This initial set of five VTEU 2009 H1N1 influenza vaccine trials will enroll about 3000 people. For more details about target enrollment, see the specific descriptions of the five study protocols at www.clinicaltrials.gov (specific links are available in the answer to question #6).

11. When will results from these trials be available?

In addition to collecting blood samples approximately 3 weeks after each vaccination, study staff will also collect samples a little over 1 week after vaccination to see if there are early indications that some individuals may already have a primed immune system. Preliminary results from these early samples in a subset of the people in these trials are expected to be available a few weeks after the trials begin.

12. How do scientists evaluate the performance of the vaccines in these trials?

To evaluate the immune response of the vaccines in these trials, the researchers will look at the level of antibodies induced by the vaccines in the volunteers using two assays: a hemagglutinin inhibition assay (a laboratory test used to measure the amount of antibody present in a sample by determining if the antibody inhibits influenza virus from attaching to red blood cells) and a microneutralization assay (a technique used to determine if the level of antibody in the sample inhibits the virus from infecting cells grown in the laboratory).

13. How will the safety of volunteers in these trials be ensured?

The VTEU study teams will be closely monitoring the health status of all volunteers for any adverse side effects. In addition, a panel of outside experts will conduct an ongoing, close review of the safety data from these trials to spot any safety concerns in real time.

14. How do these trials fit in with the trials being done by the manufacturers?

The five manufacturers who already produce U.S.-licensed seasonal vaccine are conducting their own 2009 H1N1 influenza vaccine trials under contract with HHS. The VTEU trials are intended to generate clinical data that may be used to inform policy decisions likely to affect the administration of the vaccines. For example, the NIAID-supported VTEU trials are evaluating the vaccines in some populations (for example, in children) that manufacturers may not be planning to study. In addition, the trials are intended to generate data that are outside a company’s clinical development plan but that may be needed to support licensure or use of the vaccine under Emergency Use Authorization (EUA). Issued by the U.S. Food and Drug Administration, an EUA permits either the use of an unapproved medical product or an unapproved use of an approved medical product during certain types of emergencies with specified agents.




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 http://www.niaid.nih.gov.


The National Institutes of Health (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. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

abrir aquí:
http://www3.niaid.nih.gov/news/QA/vteuH1N1qa.htm


QUESTIONS AND ANSWERS
Pediatric Trials of 2009 H1N1 Influenza Vaccine at NIAID Vaccine and Treatment Evaluation Units (VTEUs)

1. When did the trials in children begin?

On Monday, August 17, 2009, the Safety Monitoring Committee reviewed initial safety data from more than 500 volunteers enrolled in the first three trials of 2009 H1N1 influenza vaccines in adult and elderly people. The Safety Monitoring Committee determined that the pediatric trials could begin. NIAID agreed with those recommendations and authorized the two trials of 2009 H1N1 influenza vaccine in children to begin the next day.

2. Who is on the Safety Monitoring Committee?

The Safety Monitoring Committee is a panel of outside experts convened by NIAID to evaluate the safety data from these and other VTEU 2009 H1N1 influenza vaccine trials. The individuals on this independent committee are recognized experts in the fields of pediatrics, infectious diseases and vaccine practice and safety. They review and comment on the scientific study before enrollment begins. Once the study starts, the committee meets regularly to review data and safety information related to the study and is also available for ad hoc meetings as needed.

3. How many trials are being conducted with children?

At this time, the VTEUs are conducting two pediatric clinical trials of 2009 H1N1 influenza vaccines. Researchers participating in these two trials are located at several medical centers across the country (listed below).

4. What are the objectives and the design of these studies?

The two trials are enrolling children between 6 months and 17 years of age. Each trial will look at specific scientific questions:

Dosing Trial:

The dosing trial is assessing how large a vaccine dose, and how many doses of vaccine, are needed to induce an immune response that is predictive of protection.

Children enrolled in the trial received 15 or 30 micrograms of vaccine on their first visit and a second dose of the same strength of vaccine three weeks later. The trial enrolled up to 650 children at five locations nationwide (listed below).

Combination Trial:

The combination trial is testing a 2009 H1N1 influenza vaccine given together with licensed inactivated seasonal flu vaccine. The goal is to determine if 15 micrograms of 2009 H1N1 influenza vaccine can be safely administered at the same time or sequentially with 45 micrograms of the seasonal flu vaccine (containing three components with 15 micrograms of each), and if both vaccines will induce immune responses predictive of protection from future infection.

To be eligible for the combination trial, children must have previously received two doses of seasonal flu vaccine in one year or be older than 9 years. The trial enrolled up to 650 children at six locations nationwide (listed below).

5. Where are the pediatric trials taking place?

In all, 11 medical centers are participating in the pediatric clinical trials of H1N1 influenza vaccine:

The dosing trial is taking place at five locations:
Baltimore (University of Maryland School of Medicine VTEU, the lead site for this trial)
Nashville (Vanderbilt University VTEU)
Durham, NC (Duke University)
Kansas City (Children’s Mercy Hospital)
Seattle (Children’s Hospital, Seattle)
The combination trial is taking place at six locations:

Saint Louis (Saint Louis University VTEU, the lead site for this trial)
Atlanta (Emory University VTEU)
Cincinnati (Cincinnati Children’s Hospital VTEU)
Houston (Baylor College of Medicine VTEU)
Iowa City (University of Iowa VTEU)
Galveston (University of Texas Medical Branch)

6. Who makes the vaccines being tested in the pediatric trials?

Both trials are using a 2009 H1N1 flu vaccine made by Sanofi Pasteur in Swiftwater, Pennsylvania. The combination trial involves a licensed seasonal flu vaccine made by the same company.

7. Do the vaccines used in the pediatric trials contain thimerosal or adjuvants?

No. The 2009 H1N1 influenza vaccine and the seasonal influenza vaccine used in these trials do not contain thimerosal or adjuvants.

For more information, visit NIAID's Vaccine portal, where you also can find information about adjuvants and thimerosal.

8. What data did the Safety Monitoring Committee evaluate to determine that the trials could proceed in children?

The Safety Monitoring Committee assessed initial safety data from the ongoing trials of 2009 H1N1 influenza vaccines from more than 500 healthy adult and elderly volunteers.
All clinical protocols are also reviewed and approved by the U.S. Food and Drug Administration (FDA) before enrolling any volunteers.

9. Have some children enrolled in the study received a placebo injection? If so, will those children be offered the 2009 H1N1 or seasonal influenza vaccines after the trial is concluded?

No. Placebos are not being used in the pediatric trials.

10. What did early results from the dosing trial show?
Preliminary analysis of blood samples from a small group of trial participants showed that a single 15-microgram dose of a non-adjuvanted 2009 H1N1 influenza vaccine generated an immune response that is expected to be protective against 2009 H1N1 influenza virus in the majority of 10-to 17-year olds, 8 to 10 days following vaccination. Younger children generally had a less robust early response to the vaccine.

The preliminary results are based on blood samples taken 8 to 10 days after the first vaccination. Immune responses were strongest among the oldest children, those 10-to 17-years old. In this group of 25 children, a strong immune response was seen in 76 percent who received one 15-microgram dose of 2009 H1N1 influenza vaccine. Among 25 volunteers aged 3 to 9 years old, a strong immune response was seen in 36 percent of those given 15 micrograms of vaccine. In the youngest group, 20 children between 6 months and 35 months old, a single 15-microgram dose of vaccine produced a strong immune response in 25 percent of recipients.

These preliminary results were announced on September 21, 2009.

For more information, visit NIAID's Vaccine portal, where you also can find information about adjuvants and thimerosal.

For more information about influenza, including H1N1, visit NIAID's Flu portal.



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 http://www.niaid.nih.gov.


The National Institutes of Health (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. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

abrir aquí:
http://www3.niaid.nih.gov/news/QA/qaH1N1pedvax.htm