January 13, 2010
What information did FDA use to support the approval of the Intranasal Influenza A (H1N1) 2009 Monovalent Live Attenuated Vaccine?
Vaccines used in the United States must be licensed by FDA. FDA approved all of the Influenza A (H1N1) 2009 vaccines as a strain change to each manufacturer’s FDA-approved seasonal influenza vaccine. Each manufacturer is making their Influenza A (H1N1) 2009 Monovalent vaccine using their well-established, licensed egg-based manufacturing process that is used to manufacture their licensed seasonal influenza vaccine.
There is considerable experience with seasonal influenza vaccine development and production. Influenza vaccines produced by this technology have a long and successful track record of safety and effectiveness in the United States. The safety and efficacy demonstrated for the seasonal influenza vaccine, FluMist, supported the licensure of the Intranasal Influenza A (H1N1) 2009 Monovalent Live Attenuated Vaccine produced using the same process as for seasonal vaccine. All of the Influenza A (H1N1) 2009 Monovalent vaccines undergo the same rigorous testing and lot release procedures that are in place for seasonal influenza vaccines.
The regulatory pathway to licensure was discussed in an open meeting of FDA's Vaccines and Related Biological Products Advisory Committee on July 23, 2009. Presentations were made by representatives from FDA, NIH, CDC, DHHS and industry. In addition to discussion about the appropriate regulatory approach/pathway for approving the pandemic H1N1 strain change, discussions also included the design of clinical studies to determine optimal antigen dose and vaccination regimen.
How is the Intranasal Influenza A (H1N1) 2009 Monovalent Live Attenuated Influenza Vaccine (LAIV) different from the Influenza A (H1N1) 2009 Monovalent inactivated influenza vaccine?
LAIV contains attenuated (weakened) virus. The weakened strain does not cause influenza illness because it has lost virulence (disease-causing properties). The weakened viruses are cold-adapted, which means they are designed to only cause infection at the cooler temperatures found within the nose. The viruses cannot infect the lungs or other areas of the body where warmer temperatures exist. It is administered by spraying into the nose. Inactivated influenza vaccines are killed viruses and are administered via a needle into the arm.
LAIV is approved for individuals 2 through 49 years of age. Inactivated influenza vaccines, depending on the vaccine manufacturer, are approved for different age groups. Some inactivated influenza vaccines are approved for individuals 6 months of age and older, whereas others are approved for older children and adults, and some for adults only.
Viruses used for the manufacture of both vaccines are grown in eggs.
What are the side effects of H1N1 LAIV? Are the side effects of LAIV different from inactivated influenza vaccines?
Adverse events after vaccination with LAIV during clinical trials conducted in children and adolescents 2 through 17 years of age include: runny nose/nasal congestion, decreased appetite, irritability, decreased activity, sore throat, and fever.
The most common adverse events after vaccination with LAIV during clinical trials conducted in adults 18 through 49 years of age included runny nose/nasal congestion and sore throat.
In comparison, inactivated influenza vaccines, which are injected, often cause soreness, redness, tenderness and swelling at the injection site. However, sore throat and nasal congestion seen with LAIV are not typically seen with inactivated influenza vaccines.
Is LAIV as safe as inactivated influenza vaccines? Have there been any adverse events associated with the H1N1 LAIV?
Both types of influenza vaccine are safe and effective. The adverse event profiles of the 2009 H1N1 vaccines are similar to their seasonal influenza vaccine counterparts. No increase in any adverse events under surveillance has been seen in a cohort of 438,376 persons vaccinated with H1N1 products and followed prospectively through the CDC’s Vaccine Safety Datalink [VSD]. Nationwide passive surveillance with the U.S. Vaccine Adverse Event Reporting System [VAERS] demonstrates similar types and proportions of adverse events following both live, attenuated H1N1 vaccine and live, attenuated seasonal vaccine.
Detailed published data regarding H1N1 vaccine safety appears in the December 11, 2009 issue of the CDC’s Morbidity and Mortality Weekly Report. The article is publicly available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5848a4.htm. VAERS received 1,115 reports of adverse events after receipt of live, attenuated H1N1 vaccine. The majority, 95.3%, were nonserious. The remaining reports were classified as serious according to federal regulation. However, the percentage of serious adverse events after receipt of H1N1 vaccines was slightly lower than the percentage of serious adverse events after receipt of seasonal influenza vaccines. Weekly updates of H1N1 VAERS adverse event data are accessible to health care practitioners and the public at http://vaers.hhs.gov/resources/h1n1update#top.
There was a recent study published comparing the efficacy of seasonal trivalent inactivated influenza vaccine (TIV) and seasonal live, attenuated influenza vaccine (LAIV), which suggested that TIV is more effective than LAIV. Is this true?
Pre-licensure clinical trials have demonstrated the efficacy of LAIV in children two years of age and older and in adults up to the age of 50 years of age and these data are reflected in the FDA-approved label. Effectiveness was not demonstrated in individuals 50-64 years of age. Comparative studies of the effectiveness of LAIV and TIV influenza vaccines have not been required for licensure. The effectiveness of influenza vaccines depends on the age and immunocompetence of the vaccine recipient, the degree of similarity (“match”) between circulating wild-type influenza viruses in a given season and the vaccine strain, influenza activity in a given season, vaccination coverage, and the clinical outcome measured. In particular for the LAIV vaccine, previous exposure to similar influenza strains may affect the effectiveness of LAIV vaccine. Thus, age specific differences in the efficacy of TIV and LAIV vaccine may explain the observed differences in relative efficacy.
Are there certain people who should not receive the Intranasal Influenza A (H1N1) 2009 Monovalent Live Attenuated Vaccine?
The vaccine is not indicated for children less than two years of age or for adults 50 years of age and older. Clinical trial data for LAIV raised safety concerns among infants less than two years of age, as well as in children younger than five years of age with a history of recurrent wheezing. Additionally, there are no data available to support the safe and effective use in certain other populations, such as pregnant women, people with chronic medical conditions whose risk for the complications of influenza is increased, and in immunocompromised individuals.
Just as for inactivated influenza vaccines, if Guillain-Barré syndrome has occurred with any prior influenza vaccination, the decision to give LAIV should be based on careful consideration of potential benefits and risks. Both LAIV and inactivated vaccines are contraindicated for individuals with chicken egg allergy or allergy to other components of the vaccine formulation. In addition, LAIV is contraindicated for children and adolescents who are receiving aspirin therapy or aspirin-containing therapy because of the association of Reye’s syndrome with aspirin and wild-type influenza infection.
Can the live H1N1 virus in LAIV make a person sick?
The vaccine virus has been weakened and can’t cause serious illness in the way that naturally occurring influenza virus can. The vaccine can cause adverse events, most of which are mild and do not require any treatment. The most common adverse events seen with administration of H1N1 LAIV include runny nose/nasal congestion in recipients of all ages and fever in children 2 to 6years of age, and sore throat in adults.
Is the virus shed? Can the shed live virus be transmitted?
Vaccine viruses capable of infection and replication can be cultured from nasal secretions obtained from vaccine recipients. Young children may be more likely to shed vaccine virus, probably due to a lack of pre-existing immunity to influenza and inability to manage upper respiratory secretions. In a pre-licensure study, a low rate of transmission of vaccine virus was observed in healthy children in a daycare setting.
Could healthcare workers transmit it to their patients? What about the contacts of pregnant women, those with weakened immune systems, and others who should not receive the Intranasal Influenza A (H1N1) 2009 Monovalent Live Attenuated Vaccine?
FDA-approved labeling states that “the duration of vaccine virus replication and shedding have not been established.” However, guidance and recommendations for use of the 2009 H1N1 influenza vaccines in situations not specifically addressed in FDA-approved labeling is provided by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices and can be accessed at http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5810a1.htm.
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