FluMist
Encyclopedia
FluMist is a nasal spray
influenza vaccine manufactured by MedImmune
, Inc. that was first introduced in 2003. It was the first and (as of 2007) the only live attenuated vaccine for influenza available outside of Europe
. It is also called live attenuated influenza vaccine
(LAIV). In September 2009 a LAIV intranasal vaccine for the novel H1N1 influenza virus was approved. In 2011, the vaccine was approved by the European Medicines Agency
for use in the European Union
under the name Fluenz.
or pandemic
outbreaks of influenza
.
In Canada, the National Advisory Committee on Immunization (NACI), the group that advises the Public Health Agency of Canada, currently recommends that everyone aged 2 to 64 years be encouraged to receive annual influenza vaccination, and that children between the age of 6 and 24 months, and their household contacts, should be considered a high priority for the flu vaccine.
In February 2008, the U.S. Centers for Disease Control and Prevention
(CDC) Advisory Committee on Immunization Practices
(ACIP) recommended vaccination for all children and teenagers between six months and 18 years of age.
FluMist is a vaccine of demonstrated effectiveness against seasonal influenza. Reviews conducted in 2008 and 2011 suggest that FluMist may be equal to or more effective than injected influenza vaccines in children aged 6–71 months and in children aged 6–17 years.
In 2007, FluMist received additional approval from the U.S. Food and Drug Administration (FDA) extending the age groups it is approved for, to include healthy children two years old and onward. And the CDC's Advisory Committee on Immunization Practices
(ACIP), endorsed the needle-free vaccine as a good option for healthy (non-asthmatic) children aged 2 through 4 years. This extended approval supplemented approvals for children over four years of age that were already effective. The sum of these approvals is that FluMist is approved and recommended from the child's 25th month through the adult's 49th year of age.
FluMist is currently recommended for all healthy persons at least two years old and under 50 years of age wishing to protect themselves from influenza
and its complications, or to avoid spreading the flu to members of certain vulnerable groups:
For comparison, only Sanofi-Aventis
's injectable influenza vaccine is approved for children 7 months of age and older; FluMist is approved after the second year, and other injectable vaccines from four years of age onward. Injectable influenza vaccine approvals have no upper age limit, while FluMist has not yet been tested or presented for FDA approval for use by persons 50 or older.
Within the age groups they are approved for, injectable vaccines do occasionally present mild side effects such as soreness, redness, swelling, fever, and aches, and FluMist sometimes causes brief and mild symptoms such as a runny nose. Side effects of both FluMist and injected vaccines tend to be slightly more prevalent the first year, and to diminish with vaccinations given in subsequent years.
Tests against injected (killed virus) vaccinations have shown that FluMist is more effective than needle shots in preventing influenza, especially in children aged 6 to 17
but one smaller study in adults showed lower effectiveness against influenza B viruses in adults.
In past years when flu vaccine has been in short supply, healthy people were requested to abstain from vaccination early in the season, to leave the limited supply for the most vulnerable groups. Flu vaccine supplies are now abundant, and since healthy people benefit from vaccination they are now encouraged to protect themselves and others by being vaccinated.
The 2007 recommendations by the US Advisory Committee on Immunization Practices
(ACIP) include six principal changes or updates. These stress that all persons who want to reduce the risk of becoming ill with influenza or of transmitting influenza to others should be vaccinated, and that young children not previously vaccinated should be vaccinated twice, and include these specific recommendations:
In 2000, a study found FluMist be well tolerated in 57 adults with asymptomatic HIV and median CD4 counts of 541. The FluMist patient information further clarifies, "Although FluMist was studied in 57 asymptomatic or mildly symptomatic adults with HIV infection [...], data supporting the safety and effectiveness of FluMist administration in immunocompromised individuals are limited." In 2008, FluMist was tested and found safe for children suffering from HIV and taking anti-retrovirals.
However, the U.S. Centers for Disease Control state clearly that people with HIV/AIDS should not receive FluMist and that advice is augmented by the suggestion that close household contacts or caregivers of severely immunocompromised individuals should not receive FluMist due to transmission risks from individuals immunized with FluMist.
The vaccine was approved for use in the European Union by the European Medicines Agency in 2011. Marketing approval in Europe, where it will be called Fluenz, is for the prevention of seasonal influenza in children aged from two to less than 18 years, though distribution will not likely begin until 2012.
It is possible for individuals vaccinated with FluMist to spread the virus to others for up to 21 days after vaccination. For this reason it is recommended that those vaccinated with FluMist avoid close contact with individuals with weak immune systems during that time.
advance preparation to reduce human mortality in the event of an H5N1 pandemic
has begun. Modifying FluMist to serve as a specific human H5N1 vaccine is among the measures studied.
In June 2006, the National Institutes of Health
(NIH) began enrolling participants in a Phase 1 H5N1 study
of an intranasal influenza vaccine candidate based on MedImmune
's live, attenuated vaccine technology.
In September 2006 the NIH NIAID reported that inoculation with a FluMist vaccine modified to present the surface antigens of certain H5N1 variants provided broad protection against other H5N1 variants in the mouse and ferret models. Attenuated live viruses were found protective against H5N1 in mice and chickens in a 2009 study.
Although early work is focusing on the looming H5N1 threat, the CDC team led by Kanta Subbarao and others intends to eventually prepare and store surface antigens for all known strains of influenza, ready to be grafted onto the base attenuated FluMist core virus whenever a pandemic threat might emerge.
"Several trials have reported that LAIVs can boost virus-specific CTLs as well as mucosal and serum antibodies and provide broad cross-protection against heterologous human influenza A viruses." (58, 59) "[V]accine formulas inducing heterosubtypic T cell–mediated immunity may confer broad protection against avian and human influenza A viruses."
In September 2009 a LAIV intranasal vaccine for the novel H1N1 influenza virus was approved.
School of Public Health in Ann Arbor, Michigan
and later by Aviron, in Mountain View
, California
, under the sponsorship of NIH in the mid-1990s. MedImmune
, Inc. purchased Aviron in 2002, and the FDA approved FluMist in June 2003. FluMist was first made available in September 2003.
The U.S. FDA initially approved FluMist only for healthy people ages 5 to 49 because of concerns over possible side effects. Now FluMist is approved and recommended for healthy children 24 months of age and older. The FDA approved the current unfrozen refrigerated version for the same age group (ages 5–49) in August 2006 following completion of phase 3 clinical trials.
CAIV-T has been approved by the FDA and is the version offered on the market beginning in fall of 2007.
The current version of the vaccine is called CAIV-T, and is stable for storage in a refrigerator, rather than requiring freezer storage as did the originally-approved formulation. Approved for the 2007-2008 flu season, the refrigerated formulation can be distributed more economically, so that the price differential with shots (which had hampered sales of the original frozen version of FluMist) is now largely eliminated. FluMist was initially priced higher than the injectable vaccines, but sold only 500,000 of the 4 million doses it produced its first year on the market, despite a comparative shortage of flu vaccine in fall 2004. The price was sharply lowered the next year, and the company reports distributing 1.6 million doses in 2005. Because of the price drop, despite selling almost three times as many doses in 2005, the company reported $21 million in FluMist sales, compared to $48 million the previous year. Further cuts in pricing had to await FDA approval of a refrigerator-cooled FluMist formulation, as the initial formulation required freezer storage and thawing on demand before administration. Although it is positioned as a premium product, the remaining price premium for FluMist over the cost of needle-injected vaccine is small.
Nasal spray
Nasal sprays come in a variety of forms. Medicated such as Astelin, Afrin and Nasonex and natural such as Sinusoothe and Sterimar. Although delivery methods vary, most nasal sprays function by instilling a fine mist into the nostril by action of a hand-operated pump mechanism.-Antihistamine nasal...
influenza vaccine manufactured by MedImmune
MedImmune
MedImmune, LLC, headquartered in Gaithersburg, Maryland, became a wholly owned subsidiary of AstraZeneca in 2007. Since being acquired, MedImmune has remained a Maryland-based biotechnology development enterprise...
, Inc. that was first introduced in 2003. It was the first and (as of 2007) the only live attenuated vaccine for influenza available outside of Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
. It is also called live attenuated influenza vaccine
Live attenuated influenza vaccine
Live attenuated influenza vaccine is a type of influenza vaccine. It is an attenuated vaccine. This is in contrast to most influenza vaccines, which are inactivated vaccines. Both forms of vaccine are typically trivalent...
(LAIV). In September 2009 a LAIV intranasal vaccine for the novel H1N1 influenza virus was approved. In 2011, the vaccine was approved by the European Medicines Agency
European Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
for use in the European Union
European Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...
under the name Fluenz.
Groups for whom FluMist is recommended
Influenza vaccine is a cost-effective counter-measure to the threat of seasonalFlu season
Flu season is a annually-recurring time period characterized by the prevalence of outbreaks of influenza . The season occurs during the cold half of the year in each hemisphere. Influenza activity can sometimes be predicted and even tracked geographically...
or pandemic
Influenza pandemic
An influenza pandemic is an epidemic of an influenza virus that spreads on a worldwide scale and infects a large proportion of the human population. In contrast to the regular seasonal epidemics of influenza, these pandemics occur irregularly, with the 1918 Spanish flu the most serious pandemic in...
outbreaks of influenza
Influenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
.
In Canada, the National Advisory Committee on Immunization (NACI), the group that advises the Public Health Agency of Canada, currently recommends that everyone aged 2 to 64 years be encouraged to receive annual influenza vaccination, and that children between the age of 6 and 24 months, and their household contacts, should be considered a high priority for the flu vaccine.
In February 2008, the U.S. Centers for Disease Control and Prevention
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
(CDC) Advisory Committee on Immunization Practices
Advisory Committee on Immunization Practices
The Advisory Committee on Immunization Practices provides advice and guidance on effective control of vaccine-preventable diseases in the U.S. civilian population. The ACIP develops written recommendations for routine administration of vaccines to the pediatric and adult populations, along with...
(ACIP) recommended vaccination for all children and teenagers between six months and 18 years of age.
FluMist is a vaccine of demonstrated effectiveness against seasonal influenza. Reviews conducted in 2008 and 2011 suggest that FluMist may be equal to or more effective than injected influenza vaccines in children aged 6–71 months and in children aged 6–17 years.
In 2007, FluMist received additional approval from the U.S. Food and Drug Administration (FDA) extending the age groups it is approved for, to include healthy children two years old and onward. And the CDC's Advisory Committee on Immunization Practices
Advisory Committee on Immunization Practices
The Advisory Committee on Immunization Practices provides advice and guidance on effective control of vaccine-preventable diseases in the U.S. civilian population. The ACIP develops written recommendations for routine administration of vaccines to the pediatric and adult populations, along with...
(ACIP), endorsed the needle-free vaccine as a good option for healthy (non-asthmatic) children aged 2 through 4 years. This extended approval supplemented approvals for children over four years of age that were already effective. The sum of these approvals is that FluMist is approved and recommended from the child's 25th month through the adult's 49th year of age.
FluMist is currently recommended for all healthy persons at least two years old and under 50 years of age wishing to protect themselves from influenza
Influenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
and its complications, or to avoid spreading the flu to members of certain vulnerable groups:
"All healthy, non-pregnant persons age 49 yrs and younger who want to reduce the likelihood of becoming ill with influenza, or of spreading it to others who meet any of the criteria listed below:
-Working or living with at-risk people as listed in the section above.
-Healthcare personnel or other persons who provide direct care to at-risk people (except persons in close contact with severely immunosuppressed persons).
-Household contacts and out-of-home caregivers of children age 0–59m.
-Travelers who may be among people from areas of the world where there is current influenza activity (e.g., on organized tours).
-Students or other persons in institutional settings (e.g., dormitory residents)."
For comparison, only Sanofi-Aventis
Sanofi-Aventis
Sanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...
's injectable influenza vaccine is approved for children 7 months of age and older; FluMist is approved after the second year, and other injectable vaccines from four years of age onward. Injectable influenza vaccine approvals have no upper age limit, while FluMist has not yet been tested or presented for FDA approval for use by persons 50 or older.
Within the age groups they are approved for, injectable vaccines do occasionally present mild side effects such as soreness, redness, swelling, fever, and aches, and FluMist sometimes causes brief and mild symptoms such as a runny nose. Side effects of both FluMist and injected vaccines tend to be slightly more prevalent the first year, and to diminish with vaccinations given in subsequent years.
Tests against injected (killed virus) vaccinations have shown that FluMist is more effective than needle shots in preventing influenza, especially in children aged 6 to 17
but one smaller study in adults showed lower effectiveness against influenza B viruses in adults.
In past years when flu vaccine has been in short supply, healthy people were requested to abstain from vaccination early in the season, to leave the limited supply for the most vulnerable groups. Flu vaccine supplies are now abundant, and since healthy people benefit from vaccination they are now encouraged to protect themselves and others by being vaccinated.
The 2007 recommendations by the US Advisory Committee on Immunization Practices
Advisory Committee on Immunization Practices
The Advisory Committee on Immunization Practices provides advice and guidance on effective control of vaccine-preventable diseases in the U.S. civilian population. The ACIP develops written recommendations for routine administration of vaccines to the pediatric and adult populations, along with...
(ACIP) include six principal changes or updates. These stress that all persons who want to reduce the risk of becoming ill with influenza or of transmitting influenza to others should be vaccinated, and that young children not previously vaccinated should be vaccinated twice, and include these specific recommendations:
ACIP reiterates a previous recommendation that all persons, including school-aged children, who want to reduce the risk of becoming ill with influenza or of transmitting influenza to others should be vaccinated (see Box and Recommendations for Using TIV and LAIV During the 2007--08 Influenza Season).
ACIP emphasizes that immunization providers should offer influenza vaccine and schedule immunization clinics throughout the influenza season (see Timing of Vaccination).
ACIP recommends that health-care administrators consider the level of vaccination coverage among health-care personnel (HCP) to be one measure of a patient safety quality program and implement policies to encourage HCP vaccination (e.g., obtaining signed statements from HCP who decline influenza vaccination) (see Additional Information Regarding Vaccination of Specific Populations).
In 2000, a study found FluMist be well tolerated in 57 adults with asymptomatic HIV and median CD4 counts of 541. The FluMist patient information further clarifies, "Although FluMist was studied in 57 asymptomatic or mildly symptomatic adults with HIV infection [...], data supporting the safety and effectiveness of FluMist administration in immunocompromised individuals are limited." In 2008, FluMist was tested and found safe for children suffering from HIV and taking anti-retrovirals.
However, the U.S. Centers for Disease Control state clearly that people with HIV/AIDS should not receive FluMist and that advice is augmented by the suggestion that close household contacts or caregivers of severely immunocompromised individuals should not receive FluMist due to transmission risks from individuals immunized with FluMist.
The vaccine was approved for use in the European Union by the European Medicines Agency in 2011. Marketing approval in Europe, where it will be called Fluenz, is for the prevention of seasonal influenza in children aged from two to less than 18 years, though distribution will not likely begin until 2012.
Groups for whom FluMist is not recommended
- People less than 2 years of age
- People 50 years of age and over
- People with a medical condition that places them at high risk for complications from influenza, including those with chronic heart or lung disease, such as asthma or reactive airways disease
- People with medical conditions such as diabetes or kidney failure or people with illnesses that weaken the immune system, or who take medications that can weaken the immune system
- Children less than 5 years old with a history of recurrent wheezing
- Children or adolescents receiving aspirin
- People with a history of Guillain-Barré syndromeGuillain-Barré syndromeGuillain–Barré syndrome , sometimes called Landry's paralysis, is an acute inflammatory demyelinating polyneuropathy , a disorder affecting the peripheral nervous system. Ascending paralysis, weakness beginning in the feet and hands and migrating towards the trunk, is the most typical symptom...
, a rare disorder of the nervous system - Pregnant women
- People who have a severe allergy to chicken eggs or who are allergic to any of the nasal spray vaccine components
It is possible for individuals vaccinated with FluMist to spread the virus to others for up to 21 days after vaccination. For this reason it is recommended that those vaccinated with FluMist avoid close contact with individuals with weak immune systems during that time.
Testing pandemic FluMist variants
FluMist is designed to be quickly modifiable to present the surface antigens of seasonal flu. The modifiability could also allow it to be quickly customized as a vaccine against a pandemic influenza if one were to emerge. In light of the Global spread of H5N1Global spread of H5N1
The global spread of highly pathogenic H5N1 influenza in birds is considered a significant pandemic threat.While other H5N1 influenza strains are known, they are significantly different from a current, highly pathogenic H5N1 strain on a genetic level, making the global spread of this new strain...
advance preparation to reduce human mortality in the event of an H5N1 pandemic
Human mortality from H5N1
Human mortality from H5N1 or the human fatality ratio from H5N1 or the case-fatality rate of H5N1 refer to the ratio of the number of confirmed human deaths resulting from confirmed cases of transmission and infection of H5N1 to the number of those confirmed cases...
has begun. Modifying FluMist to serve as a specific human H5N1 vaccine is among the measures studied.
In June 2006, the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
(NIH) began enrolling participants in a Phase 1 H5N1 study
H5N1 clinical trials
H5N1 clinical trials are clinical trials concerning H5N1 vaccines. They are intended to discover pharmacological effects and identify any adverse reactions the vaccines may achieve in humans.-Current status of H5N1 candidate vaccines:...
of an intranasal influenza vaccine candidate based on MedImmune
MedImmune
MedImmune, LLC, headquartered in Gaithersburg, Maryland, became a wholly owned subsidiary of AstraZeneca in 2007. Since being acquired, MedImmune has remained a Maryland-based biotechnology development enterprise...
's live, attenuated vaccine technology.
In September 2006 the NIH NIAID reported that inoculation with a FluMist vaccine modified to present the surface antigens of certain H5N1 variants provided broad protection against other H5N1 variants in the mouse and ferret models. Attenuated live viruses were found protective against H5N1 in mice and chickens in a 2009 study.
Although early work is focusing on the looming H5N1 threat, the CDC team led by Kanta Subbarao and others intends to eventually prepare and store surface antigens for all known strains of influenza, ready to be grafted onto the base attenuated FluMist core virus whenever a pandemic threat might emerge.
"Several trials have reported that LAIVs can boost virus-specific CTLs as well as mucosal and serum antibodies and provide broad cross-protection against heterologous human influenza A viruses." (58, 59) "[V]accine formulas inducing heterosubtypic T cell–mediated immunity may confer broad protection against avian and human influenza A viruses."
In September 2009 a LAIV intranasal vaccine for the novel H1N1 influenza virus was approved.
History
FluMist was originally developed by Hunein "John" Maassab, Professor of Epidemiology at the University of MichiganUniversity of Michigan
The University of Michigan is a public research university located in Ann Arbor, Michigan in the United States. It is the state's oldest university and the flagship campus of the University of Michigan...
School of Public Health in Ann Arbor, Michigan
Michigan
Michigan is a U.S. state located in the Great Lakes Region of the United States of America. The name Michigan is the French form of the Ojibwa word mishigamaa, meaning "large water" or "large lake"....
and later by Aviron, in Mountain View
Mountain View, California
-Downtown:Mountain View has a pedestrian-friendly downtown centered on Castro Street. The downtown area consists of the seven blocks of Castro Street from the Downtown Mountain View Station transit center in the north to the intersection with El Camino Real in the south...
, California
California
California is a state located on the West Coast of the United States. It is by far the most populous U.S. state, and the third-largest by land area...
, under the sponsorship of NIH in the mid-1990s. MedImmune
MedImmune
MedImmune, LLC, headquartered in Gaithersburg, Maryland, became a wholly owned subsidiary of AstraZeneca in 2007. Since being acquired, MedImmune has remained a Maryland-based biotechnology development enterprise...
, Inc. purchased Aviron in 2002, and the FDA approved FluMist in June 2003. FluMist was first made available in September 2003.
The U.S. FDA initially approved FluMist only for healthy people ages 5 to 49 because of concerns over possible side effects. Now FluMist is approved and recommended for healthy children 24 months of age and older. The FDA approved the current unfrozen refrigerated version for the same age group (ages 5–49) in August 2006 following completion of phase 3 clinical trials.
CAIV-T has been approved by the FDA and is the version offered on the market beginning in fall of 2007.
The current version of the vaccine is called CAIV-T, and is stable for storage in a refrigerator, rather than requiring freezer storage as did the originally-approved formulation. Approved for the 2007-2008 flu season, the refrigerated formulation can be distributed more economically, so that the price differential with shots (which had hampered sales of the original frozen version of FluMist) is now largely eliminated. FluMist was initially priced higher than the injectable vaccines, but sold only 500,000 of the 4 million doses it produced its first year on the market, despite a comparative shortage of flu vaccine in fall 2004. The price was sharply lowered the next year, and the company reports distributing 1.6 million doses in 2005. Because of the price drop, despite selling almost three times as many doses in 2005, the company reported $21 million in FluMist sales, compared to $48 million the previous year. Further cuts in pricing had to await FDA approval of a refrigerator-cooled FluMist formulation, as the initial formulation required freezer storage and thawing on demand before administration. Although it is positioned as a premium product, the remaining price premium for FluMist over the cost of needle-injected vaccine is small.
External links
- FluMist nasal flu vaccine - Official website
- FluMist information on University of Michigan, School of Public Health website
- Live Attenuated Vaccine in Russia presentation on Russian live influenza vaccines since 1961
- CDC Vaccine Information Statement Live, Attenuated Influenza Vaccine
- CDC Vaccine Information Statement 2009 H1N1 LAIV
- Summary of the European public assessment report (EPAR) for Fluenz