FluMist is a nasal spray influenza vaccine manufactured by MedImmune, Inc. that was first introduced in 2003. It is live virus vaccine that has flu viruses that have been attenuated (weakened). It is also called live attenuated influenza vaccine (LAIV).
October 2019 – 50 Years Ago in The Journal of Pediatrics
February 2019 – Live Attenuated Influenza Vaccine: Will the Phoenix Rise Again? “Why did LAIV4 vaccine effectiveness performance decline, and can it recapture its past performance when it was a trivalent formulation?” Potential causes were reviewed at the 2016 World Health Organization meeting on LAIV effectiveness.”
February 2019 – AAP, ACIP’s previous FluMist recommendations supported by 2013-2016 data
February 2019 – Repeated IIV may increase protection against respiratory illness in kids
January 2018 – Genetic mutation in FluMist could be altered to restore effectiveness “It’s not clear exactly why it has failed but this mutation we identified could be used to make that component of the vaccine a little stronger, thereby improving vaccine efficacy.”
FluMist Quadrivalent Vaccine package insert
VAERS Found 1564 cases where Vaccine is FLUN4
July 24, 2017 – Influenza vaccines effectiveness 2013–14 through 2015–16, a test-negative study in children “6779 children were enrolled in the three seasons. Overall, 27.2% received an influenza vaccine (87.1% IIV3 or IIV4 and 12.9% LAIV4), and 15.6% tested positive for influenza (77.9% A). IIV3 was predominantly used in 2013–14 and IIV4 in 2014–15 and 2015–16.IIV3 and IIV4 had comparable VE over the three seasons (60%, 57% and 53%) and performed similarly against influenza A and B and both age-groups. LAIV4 performed poorly for influenza A (15%, 37% and 48%) but better for influenza B (100%, 56% and 100%), especially among children 5–17 years of age with VE = 100% (95%CI: 55, 100).”
- It is time to think beyond protecting individuals to protecting communities.
- Test Negative study designs are biased against vaccines that protect communities.
- The ACIP needs to incorporate other study designs when evaluating flu vaccines.
February 22, 2017 – Improving the selection and development of influenza vaccine viruses – Report of a WHO informal consultation on improving influenza vaccine virus selection, Hong Kong SAR, China, 18–20 November 2015 “Advances in next generation sequencing and whole genome sequencing of influenza viruses were also discussed, along with associated developments in synthetic genomics technologies, evolutionary analysis and predictive mathematical modelling.”
August 17, 2016 – Adverse events following pandemic influenza A (H1N1) 2009 monovalent and seasonal influenza vaccinations during the 2009–2010 season in the active component U.S. military and civilians aged 17–44 years reported to the Vaccine Adverse Event Reporting System “Vaccination coverage was more than four times higher for MIV and more than twenty times higher for LAIV3 in the military than in the civilian population. The reporting rate of serious AE reports following MIV in service personnel (1.19 per 100,000) was about half that reported by the civilian population (2.45 per 100,000). Conversely, the rate of serious AE reports following LAIV3 among service personnel (1.32 per 100,000) was more than twice that of the civilian population. Although fewer military AEs following MIV were reported overall, the rate of Guillain–Barré Syndrome (GBS) (4.01 per million) was four times greater than that in the civilian population. (1.04 per million).
March 2016 – A Single Mutation at PB1 Residue 319 Dramatically Increases the Safety of PR8 Live Attenuated Influenza Vaccine in a Murine Model without Compromising Vaccine Efficacy “The live attenuated influenza vaccine (LAIV) is preferentially recommended for use in most children yet remains unsafe for the groups most at risk.”
July 31, 2015 – Self-administration of intranasal influenza vaccine: Immunogenicity and volunteer acceptance “In outbreak settings, mass vaccination strategies could maximize health protection of military personnel. Self-administration of live attenuated influenza vaccine (LAIV) may be a means to vaccinate large numbers of people and achieve deployment readiness while sparing the use of human resources.” Comment: Not only can you not sue, now you have no way to prove you even received the vaccine.
December 11, 2014 – Live-attenuated influenza virus increases pneumococcal translocation and persistence within the middle ear “Recently, vaccination with live attenuated influenza virus (LAIV) was reported to enhance subclinical bacterial colonization within the nasopharynx, similar to IAV. Although LAIV does not predispose to bacterial pneumonia, whether it may alter bacterial transmigration towards the middle ear, where it could have clinically relevant implications, has not been investigated.”…”When colonization followed LAIV inoculation, a minimum LAIV incubation period of four days was required before bacterial transmigration commenced.”
November 25, 2014 – The Longevity of B & T cell responses after live attenuated influenza vaccination in children (pdf) “The frequencies of H3N2-specific IgG+ MBCs were maintained at day 180 (p<0.01) and decreased at day 360, but remained higher than day 0. We did not detect increased levels of IgA+ MBCs to H3N2 at any time point post-vaccination, in contrast IgM+ MBCs increased significantly at all time points (p<0.01).”…”The magnitude of the Th1 cytokine responses induced after LAIV vaccination was lower than observed in adult subjects after intramuscular vaccination with candidate pandemic vaccines. Differences in the route of administration (intramuscular or intranasal) and formulation with the adjuvant in immunologically naïve subjects, could partly explain the superiority of the parenteral vaccine at inducing a Th1 response in peripheral blood. However, in children LAIV has been shown to be a better inducer of T cell responses than TIV.”
September 11, 2014 – Did Narcolepsy Occur Following Administration of AS03-Adjuvated A(H1N1) Pandemic Vaccine in Ontario Canada? A Review of Post-Marketing Safety Surveillance Data “This report represents the first published post-marketing assessment from Canada of reports to a passive AEFI surveillance system on narcolepsy following receipt of the AS03-adjuvanted influenza A(H1N1) pandemic vaccine Arepanrix. No reports of narcolepsy were identified. Given the lack of safety signal to date from Arepanrix, continued investigation of differences between Arepanrix and Pandemrix and subsequent risk of narcolepsy appears to be indicated. However, in light of the limitations of passive surveillance to detect a signal in this instance, validation using other data sources is prudent.”
March 21, 2014 – Oral retinyl palmitate or retinoic acid corrects mucosal IgA responses toward an intranasal influenza virus vaccine in vitamin A deficient mice “The studies described here tested the hypothesis that VAD may also impair immune responses after FluMist vaccinations. Results show that (i) IgA-producing antibody forming cells (AFCs) are significantly reduced following FluMist vaccination in VAD mice, and (ii) oral doses of either retinyl palmitate or retinoic acid administered on days 0, 3, and 7 relative to vaccination rescue the response. Data encourage the conduct of clinical studies to determine if there is FluMist vaccine weaknesses in human VAD populations and to test corrective supplementation strategies.
May 20, 2011 – Intranasal Immunization with Recombinant HA and Mast Cell Activator C48/80 Elicits Protective Immunity against 2009 Pandemic H1N1 Influenza in Mice (full text) “While this novel approach has several obvious advantages over the conventional approaches, it also faces the same drawbacks similar to all of the other live attenuated vaccines. The major ones include its nature of instability which may result in mutant back to the pandemic strain, and potential risk of development of novel chimeric strains between the vaccine and wild-type viruses.”
January 1, 2011 – Potent CD8+ T-Cell Immunogenicity in Humans of a Novel Heterosubtypic Influenza A Vaccine, MVA−NP+M1 “In contrast, a trial of the cold-adapted influenza virus vaccine, FluMist, found that although it could induce modest T-cell responses in children, it did not significantly boost T-cell responses to influenza in adults with T-cell responses induced by natural exposure”
August 2, 2010 – Flu season is coming, vaccine is on the way “The spray vaccine will be available in every state but South Dakota. Last year, FluMist was given to approximately a third of the children ages 2 to 18. Parents of kids who did not get last year’s H1N1 vaccine should ask their doctors about giving two doses of this year’s vaccine.”
April 12, 2010 – Immune mechanisms of protection: can adjuvants rise to the challenge? “FluMist, which is also modified each year, although this vaccine may activate cross-reactive CD8+ T cells, at least in children. CD8+ T cells recognize less variable parts of the virus – for example, in the core proteins [23-30] – and may provide a more cross-reactive response that could be induced by new vaccines.”
April 1, 2010 – Assessment of the efficacy of commercially available and candidate vaccines against a pandemic H1N1 2009 virus. “Surprisingly, FluMist was associated with a slight increase in mortality and greater lung damage, which correlated with early up-regulation of interleukin-10.”
September 24, 2009 – Comparative Efficacy of Inactivated and Live Attenuated Influenza Vaccines (full text) “Overall, in 2007–2008, the inactivated vaccine was 50% more efficacious than the live attenuated vaccine in the only adult population in which both vaccines are approved for use. As before, the exact explanation for age-specific differences in efficacy is a matter of speculation, but these differences could be related to the inability of the live attenuated viruses to infect some adults because of their past exposure to similar strains.”
August 20, 2009 – AstraZeneca to buy MedImmune for $15 billion“Sales of FluMist have been limited since it entered the U.S. market in 2003 because regulators restricted use to healthy people ages 5 to 49, a group outside the target population for flu vaccination. Manufacturing violations delayed U.S. approval for children ages 2 to 5 until September 2007.”
July 30, 2009 – Nasal Vaccine Holds Promise Against Swine Flu “If nasal spray vaccines emerge as a central player against swine flu, it would represent a reversal of fortune for MedImmune’s efforts in the field. As a vaccine for seasonal influenza, its FluMist has been a flop from a marketing standpoint, accounting for only a few percent of the inoculations Americans receive each year.”
July 23, 2009 – Lack of sprayers hampers MedImmune’s bumper vaccine Company can make 200 million doses. But only 40 million devices on hand to deliver vaccine. Nose drops possible.
July 13, 2009 – MedImmune gets second H1N1 flu contract “MedImmune won the additional $61 million contract from the U.S. Department of Health and Human Services, six weeks after it accepted a $90 million contract from the agency to manufacture ingredients for a potential vaccine for the H1N1 virus, which had been widely dubbed as the swine flu.”
June 17, 2009 – Mass vaccination program could target schools “The U.S. government has yet to say whether or not it will roll out a mass vaccination program against swine flu this fall, but it appears increasingly likely. Health and Human Services Secretary Kathleen Sebelius says that schools will be a logical place to start.”
March 4, 2009 – In Adults, Shots Are Best for Flu “In 2004-05, military personnel who took the inhaled vaccine were actually more likely to end up in the hospital with influenza or pneumonia than those who received no vaccination, the study found.”
December 2008 – Organ distribution of transgene expression following intranasal mucosal delivery of recombinant replication-defective adenovirus gene transfer vector “Furthermore there has been an interest in developing effective mucosal-deliverable genetic vaccines against other infectious diseases. However, there is a concern that intranasally delivered recombinant viral-based vaccines may disseminate to the CNS via the olfactory tissue.”…”These experimental findings support the efficaciousness of intranasal adenoviral-mediated gene transfer for the purpose of mucosal immunization and suggest that it may not be of significant safety concern.”
October 2008 – The cold adapted and temperature sensitive influenza A/Ann Arbor/6/60 virus, the master donor virus for live attenuated influenza vaccines, has multiple defects in replication at the restrictive temperature. “Our studies demonstrate that restrictive replication of MDV-A at the non-permissive temperature occurs in multiple steps of the virus replication cycle.”
August 2008 – Adverse events associated with intranasal influenza vaccine in the United States “The safety of LAIV in individuals with unstable asthma and egg allergy has not been established and it should be avoided in these populations. For patients with unstable asthma, TIV should remain the therapy of choice.”
November 2007 – Comparative Immunogenicities of Frozen and Refrigerated Formulations of Live Attenuated Influenza Vaccine in Healthy Subjects “As expected, the most robust immunogenicity was seen in children 5 to 8 years of age who were seronegative for the influenza vaccine strains before vaccination.”
October 25, 2007 – Phenotypic properties resulting from directed gene segment reassortment between wild-type A/Sydney/5/97 influenza virus and the live attenuated vaccine strain. “Progeny viruses possessing new genotypes might arise from genetic reassortment between circulating wild-type (wt) and vaccine strains, but it will be difficult to predict whether they will be viable or exhibit novel properties.”
May 2007 – Bioaerosol sampling for the detection of aerosolized influenza virus. “Due to a lack of empirical data, aerosol transmission of influenza is often questioned. Using FluMist, we demonstrated that a newly developed bioaerosol sampler is able to recover and size fractionate aerosolized viral particles. This sampler should be an important tool for studying viral transmission in clinical settings and may significantly contribute towards understanding the modes of influenza virus transmission.”
April 2007 – Diagnostic discrimination of live attenuated influenza vaccine strains and community-acquired pathogenic strains in clinical samples. “Live vaccines can generate false-positive results on common influenza assays including reverse transcriptase-PCR (RT-PCR), culture and antigen tests. This threatens the integrity of epidemiological data and may misdirect treatment and control efforts. We report the development of RT-PCR tests that distinguish live FluMist vaccine (FMV) strains from circulating influenza strains in clinical samples. Primers were validated using influenza-positive samples from unvaccinated patients, packaged FMV, and one PCR-positive asymptomatic vaccine.”
August 2006 – The impact of mass school immunization on school attendance. “Four Title 1 elementary schools participated in the study. Students at 2 schools were offered free FluMist immunizations on site, and students at 2 control schools were not. Compliance on receiving FluMist was measured on the percentage of students participating after evaluating for medical exclusions.”
December 7, 2005 – Adverse Events Reported Following Live, Cold-Adapted, Intranasal Influenza Vaccine (full text) “Fifty-four reports (12%) were classified as allergic events. 7 reports were possible anaphylaxis events, including 4 in individuals who developed throat swelling (2 reported as serious) and 1 serious event in an individual who reported periorbital swelling. There were 47 reports of other allergic symptoms, mainly rash, urticaria, or edema, mostly in the face and neck. There were 217 reports (47%) of respiratory events (Table). Sixty-seven events were influenza like illnesses; There were 10 reports of pneumonia with onset intervals between 1 and 45 days after vaccination. Two of them, 1 in a 30-year-old man with onset 7 days after vaccination and 1 in a 10-year-old boy with onset 2 days after vaccination, resulted in hospitalization. In 3 other pneumonia events (in a 9-year-old boy, a 13-year-old boy, and a 9-year-old girl) the patients were not hospitalized, but were reported as serious events. There were 22 reports of possible secondary transmission of the vaccine virus from vaccinees to nonvaccinees. Ten neurological events (2%) were reported, and 7 were reported as serious. Ear, Nose, Throat, and Ocular Symptoms 18 reports 1 (serious) report of retinal hemorrhage in a 9-year-old boy 1 day after vaccination. There were 73 reports (16%) involving individuals for whom the vaccine was not indicated according to the product label.”
June 2005 – Improvement of Influenza A/Fujian/411/02 (H3N2) Virus Growth in Embryonated Chicken Eggs by Balancing the Hemagglutinin and Neuraminidase Activities, Using Reverse Genetics “To confirm that the HA and NA segments of these H3N2 strains controlled virus replication in eggs and cell culture, the HA and NA gene segments were reassorted with the internal gene segments of the cold-adapted A/Ann Arbor/6/60 strain, the master donor virus for live attenuated influenza FluMist vaccines (MDV-A) to generate three 6:2 reassortant viruses. Replication of these three viruses was evaluated in MDCK cells and embryonated chicken eggs. The 6:2 A/Fujian showed a lower titer (6.2 log10 PFU/ml) than the 6:2 A/Sendai (7.1 log10 PFU/ml) and A/Wyoming (7.0 log10 PFU/ml) in MDCK cells.”
February 2004 – Safety of cold-adapted live attenuated influenza vaccine in a large cohort of children and adolescents. “For reactive airway disease a significant increased relative risk was observed in children 18 to 35 months of age with a relative risk of 4.06 (90% confidence interval, 1.29 to 17.86) in this age group. The individual diagnostic categories of upper respiratory infection, musculoskeletal pain, otitis media with effusion and adenitis/adenopathy had at least one analysis that achieved a significant increased risk ratio. All of these events were infrequent.”
October 1, 2004 – Safety, Efficacy, and Effectiveness of Live, Attenuated, Cold-Adapted Influenza Vaccine in an Indicated Population Aged 5–49 Years “The placebo consisted of egg allantoic fluid, which was indistinguishable from the vaccine by sight, taste, and smell. The new analyses were limited to subjects 5–49 years of age (i.e., the age range recommended in the FluMist package insert) who received either the vaccine or the placebo, and the data for this subset of subjects were compared with the data for the study population as a whole.”
2004 – Role of influenza vaccine for healthy children in the US. “For the 2004-5 season, CAIV-T is likely to be only modestly more expensive (average wholesale price: 16.50 US dollars for non-returnable doses, 23 US dollars for returnable doses) than TIV. The practitioner must consider the benefits of FluMist compared with its likely higher vaccine cost and the issues of reimbursement among multiple insurers.”
September 26, 2003 – Using Live, Attenuated Influenza Vaccine for Prevention and Control of Influenza
2003 – Influenza virus vaccine live intranasal–MedImmune vaccines: CAIV-T, influenza vaccine live intranasal. Comment: Extensive information in this link about money used to produce and distribute FluMist. Very long article.
September 2003 – Demystifying FluMist, a new intranasal, live influenza vaccine (pdf) “Moreover, since people vaccinated with live attenuated virus may shed live virus in their nasal secretions, we do not yet know what risk this will pose to our aging population and the growing number of immunocompromised patients.”
2003 – Using live, attenuated influenza vaccine for prevention and control of influenza: supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP). “Among adults, runny nose or nasal congestion (28%–78%), headache (16%–44%), and sore throat (15%–27%) have been reported more often among vaccine recipients than placebo recipients (16,23,24). In one clinical trial (16), among a subset of healthy adults aged 18–49 years, signs and symptoms reported more frequently among LAIV recipients (n = 2,548) than placebo recipients (n = 1,290) within 7 days after each dose included cough (13.9% versus 10.8%); runny nose (44.5% versus 27.1%); sore throat (27.8% versus 17.1%); chills (8.6% versus 6.0%); and tiredness/weakness (25.7% versus 21.6%).”
2003 – Influenza Virus Vaccine Live Intranasal – MedImmune Vaccines: CAIV-T, Influenza Vaccine Live Intranasal. “In 1999, Aviron entered into an agreement with Wyeth-Lederle Vaccines for worldwide collaboration in the marketing of FluMist(TM). Under the $US400 million agreement, Aviron granted Wyeth-Lederle Vaccines exclusive worldwide rights to market FluMist(TM). Wyeth-Lederle Vaccines and Aviron (now Med-Immune Vaccines) will co-promote FluMist(TM) in the US, while Wyeth-Lederle Vaccines will have the exclusive right to market the product ex-US. Wyeth will hold marketing rights for up to 11 years.”
2000 – Genotypic Stability of Cold-Adapted Influenza Virus Vaccine in an Efficacy Clinical Trial “The FluMist vaccine appeared to be genotypically stable after replication in the human host. All viruses detected during the 2-week postvaccination period were shed vaccine viruses and had maintained the 6/2 genotype.”