Talk:Live attenuated influenza vaccine

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The below authoritative and succinct summation of FluMist live virus benefits comes from the Center for Infectious Disease Research And Policy CIDRAP and summarizes the state of the art for seasonal live vaccines before quickly moving to consideration of pandemic-specific live-virus vaccination development implications (The weakened FluMist carrier virus with the pandemic surface antigens cobbled on).

The CIDRAP summary references a 2004 report by Belshe et al. in which FluMist vaccination provided broad immunity, including significantly reducing adult risk of severe fevers and fevers with respiratory infection (apparently, there were no specific influenza cultures taken) and also reducing days taken off work sick. The advantages to adults persisted even in the second year of the study when the circulating strain differed from the strains used to prepare that season's vaccines. The full CIDRAP article appears at

http://www.cidrap.umn.edu/cidrap/content/influenza/panflu/news/nov0107panvax6.html

The FluMist section is as follows (I supplied the footnote giving a direct hyperlink in wikipedia form to the "Belshe 2004" article referenced by CIDRAP.)

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(begin quote)

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Pros and cons of live vaccines

Live-attenuated vaccine has been the Cinderella of the seasonal flu vaccine world, struggling for market share since it was introduced in 2003 by MedImmune (now part of AstraZeneca). Even during flu-shot shortages, its acceptability was hampered by restrictive FDA indications limiting its use to 5- to 49-year-olds, as well as a formula that required physicians to keep it frozen (see Bibliography: Rosenwald 2007). The vaccine was relaunched this year with a new formula that requires only refrigeration, along with a broadened indication permitting use in children as young as 2 years old, backed by research showing that it protected young children better than a shot (see Bibliography: Belshe 2007).

Because they contain live virus, live-attenuated vaccines provoke multiple types of immunity. In studies they have been shown to protect against both the strains from which vaccine candidates were derived and against drifted (slightly mutated) strains as well—characteristics that make them highly appealing to pandemic planners (see Bibliography: Belshe 2004).^[1] They also grow in eggs at a much higher volume than inactivated vaccines (see Bibliography: Monto 2007). But their live-virus content is responsible for the vaccines' greatest potential danger: the possibility that they might lead to reassortment between the vaccine virus and circulating flu strains.

"Although such an event may not be of concern in the face of widespread disease from a pandemic strain of influenza, it would clearly be an unfavorable outcome if the threatened pandemic did not materialize," Catherine Luke and Kanta Subbarao of the National Institutes of Health (NIH) wrote last year. They called for clinical trials of live-attenuated pandemic vaccine candidates in which, to eliminate the risk of reassortment, participants would be kept in inpatient isolation. "The risk for reassortment must be carefully considered by public health authorities before a decision is made to introduce a live, attenuated vaccine in a threatened pandemic," they stated (see Bibliography: Luke 2006)."

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(end quote)

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"Seasonal Flu Vaccination May Offer Partial Immunity to H5N1" reports Eric Toner, M.D. summarizing research studies revealing the protective effect of seasonal flu vaccinaton against H5N1. Dr. Toner reports for Clinitians' Biosecurity Network. Dr.Toner's report is available at: http://www.upmc-cbn.org/report_archive/2007/02_February_2007/cbnreport_02212007.html

At least two separate human studies to date indicate that annual flu shots may be protective against H5N1. In one, scientists from St. Jude's, summarize findings in animals and humans and conclude that

"Overall, these findings raise the possibility that seasonal influenza vaccination may provide some protection against pandemic H5N1l."

RESEARCH ARTICLE

Cross-Reactive Neuraminidase Antibodies Afford Partial Protection against H5N1 in Mice and Are Present in Unexposed Humans http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371%2Fjournal.pmed.0040059&ct=1&SESSID=1386b277eb2b6128495454737b76f5d2

These studies suggest that it is prudent for individuals to seek vaccination for themselves and their families, and for governments to promote wide vaccination to create a herd immunity effect to slow contagion until more specific vaccines can be developed.

Aside from developing a pandemic-specific vaccine (the benefits and risks of which are explored in the above CIDRAP note) it is possible that the long-lasting immune response to FluMist may be broad enough in scope to provide some protection, albeit unknown and probably weak, against an "bird flu" pandemic (e.g. an H5N1 influenza Type-A that has become human adapted) .

First, inoculation with a live weakened influenza may serve to protect against a Type-A H5N1 "bird flu" influenza pandemic that breaks out the same year because fighting off any live Type-A influenza virus gives the immune system strong and long-lasting immunity against other Type-A influenza. FluMist inoculation actually lets the inoculated person's immune system gain experience fighting off an actual flu with the surface antigens of the three flus selected for vaccination that year. The immune system thus gains experience similar to that it would gain fighting off a three tiny weakened flus -- two Type-A flus and one Type-B flu. There is good reason to hope that the resultant immunity would be broad -- it is almost unheard-of for a person with a functioning immune system to come down with any form of influenza a second time within a year of catching any other form. Epidemiologists well recognize this effect, because as a result flu years tend to alternate with either an H3N2 strain or an H1N1 type influenza strain predominating, almost to the exclusion of the other. This suggests that infection with one, (In recent years often H3N2), confers residual immunity to the other (recently H1N1), so that the one that breaks out first and reaches the susceptible population leaves that population (after fight off the first Type-A influenza to emerge) with an immunity broad enough to prevent the other strain from getting a start. This well-recognized effect directly affects vaccine formulation. Because there is no certainty in advance whether the coming season will be an H2N3 season or an H1N1 season, each year's flu vaccinations, FluMist and needle delivery alike, include both an H2N3 and an H1N1 Type-A influenza (as well as one Type-B). (The two Type-A strains are the H2N3 and H1N1 strains, respectively, that are deemed to be the most likely candidate for breaking out during the season ahead).

Second, and related, FluMist inoculation results in a three-prong immune reaction resulting in enhanced immune function against all flus at the mucosal, blood (humoral) and cellular level. This immune reaction has been shown in some studies to be broad enough to give at least some protection against even influenza A strains different from the ones included in preparing that year's vaccination. It is unknown whether this immunity might extends to an H5N1 strain, but there no reason to show that it would not. While humoral immunity (blood antibodies) tends to be somewhat strain-specific, mucosal and cellular immunity may be much broader. Additionally, young children are immuno-naive as to common flus, while adult immune systems have generally grown more sophisticated through prior exposure. Recent studies have shown that in this immuno-naive group, FluMist was markedly more effective at reducing influenza infection. A pandemic is a pandemic specifically because the entire population is immuno-naieve to the novel emergent strain, to which even adults have had no prior exposure. If FluMist protects the immuno-naive through non-strain-specific immunity, it might logically provide some protection against an H5N1 strain. As set out below, the blood of adults immunized against seasonal flu shows immune activity against H5N1, and animals nasally vaccinated against seasonal flu survived H5N1 challenge when unvaccinated animals did not.

Both seasonal flu vaccines (including FluMist) include an H1N1 strain with its N1 antigen, and "bird flu" H5N1 also has an N1 antigen. Italian scientists were curious whether the inclusion of an N1 antigen from each season's H1N1 might result in protection against the N1 antigen in an H5N1 strain. An experiment was done exposing the blood of vaccinated and unvaccinated humans to H5N1 (in a test tube) and the blood of vaccinated humans showed more immune response. "We also observed that seasonal vaccination is able to raise neutralizing immunity against influenza (H5N1) in a large number of donors." http://www.cdc.gov/eid/content/14/1/121.htm^[1]

Third in mice, a test found that mice immunized against the seasonal influenza developed substantial immunity against H5N1.

Cross-protection against H5N1 influenza virus infection is afforded by intranasal inoculation with seasonal trivalent inactivated influenza vaccine. PMID 17922395

http://www.newscientist.com/channel/health/bird-flu/mg19626273.700-drug-brings-hope-for-a-universal-flu-vaccine.html In this experiment, dead influenza A viruses from the H1N1 and H3N2 families in combination with Ampligen was administered nasally to mice. These are seasonal flu antigens, not pandemic H5N1 antigens. When the researchers then infected the mice with H5N1, the unvaccinated mice all died, but half or more of the nasally vaccinated mice lived. Only nasal vaccination was effective; "Subcutaneous inoculation did not induce a cross-reactive IgA response and did not afford protection against H5N1 viral infection. PMID 17922395" Immune response developed from nasal administration of ordinary seasonal flu antigens with Ampligen was protective against H5N1. By extension, one could hope that FluMist's inclusion of seasonal antigens taken from each season's H1N1 and H3N2 might result in immunity broad enough (and long-lasting enough) to provide FluMist-vaccinated persons with at least some protection against an H5N1 strain. This animal study supports breadth of immunity, particularly perhaps that elicited by an N1 antigen, as a third possible mechanism by which seasonal FluMist inoculation might provide at least some protection against an H5N1 "bird flu" pandemic when one emerged, and without the long delay inherent in current vaccination schemes.

Fourth, FluMist demonstrated broad protection against mismatched influenza A strains in at least two studies:

In a two-year, multicenter, randomized, double-blind placebo-controlled trial (conducted between 1996-1998) in children 24 months-71 months of age, FluMist provided comparable protection in a year with matched strains (95 percent protection -- year two) and a year with mismatched strains (87 percent protection -- year two). The mismatched strain that circulated during the studied season was A/Sydney (H3N2).

In a head-to-head study conducted during the 2004-2005 influenza season that included over 4,000 children between two and five years of age, when looking specifically at strains that were mismatched, there were 54.2 percent fewer cases of flu in children who received FluMist versus those that received the flu shot (Attack rate 3.2 percent vs 7.1 percent, respectively). The mismatched strains that circulated during the studied season were A/California-like (H3N2), B/Florida and B/Victoria lineage strains.

This broad immunity may extend to H5N1, as the other studies above suggest. —Preceding unsigned comment added by 69.3.11.152 (talk) 23:34, 28 February 2008 (UTC)

Finally, in addition to directly providing some immune protection against H5N1, vaccination with seasonal Flumist may also pre-prime the immune system, and allow the vaccinated person to develop immunity quickly when later vaccinated against H5N1. This has the potential to eliminate the wait of 6 weeks and the second vaccination required before protective immunity can develop under the current H5N1 vaccination protocols. Ferrets vaccinated with seasonal Flumist showed a robust immune response when vaccinated 40 days later with an H5N1 vaccine, and developed immunity. The control group included ferrets that had not been primed with Flumist, and was not similarly protected. Seasonal flu vaccine may help in fight against H5N1 http://news.yahoo.com/s/nm/20080125/hl_nm/birdflu_vaccine_dc_1;_ylt=A0WTUfIjPJpHKygBcAmTvyIi Fri Jan 25, 11:36 AM ET

The possible pre-established immunity suggested by these studies might protect the vaccinated individuals and their families, and a large percentage of vaccinated in the population might also slow the progression of a pandemic through the general population, allowing more time for vaccines specific to an emergent pandemic to be developed and applied.

—Preceding unsigned comment added by 67.101.66.241 (talk) 00:21, 5 November 2007 (UTC)

After noting Flumist is not approved for

People 50 years of age and over"

the footnote mis-states the current approved ages, stating:

(ref) The vaccine continues to be recommended for healthy persons ages 5-49 years who are not pregnant. http://www.cdc.gov/flu/about/qa/nasalspray.htm (/ref)"

In fact, the vaccine is now recommended for healthy persons two through 49 years of age, inclusive.

The above factually inaccurate statement of the age range is also somewhat out-of-place and unnecessary in a section about whom the vaccine is not approved for. One appropriate step might be to simply remove the superfluous and inaccurate footnote.

Might a person knowledgeable about the actually approved and recommended age range and a sense of stylistic concision attempt an appropriate edit?

—Preceding unsigned comment added by 69.3.11.152 (talk) 00:04, 29 February 2008 (UTC)

I understand that it can be adapted to present antigens from any circulating virus, and I understand that receiving the trivalent vaccine may boost your resilience to other subtypes; however, the first statement of the "Groups for whom..." section needs a qualifier to be true. We do not know what antigens pandemic influenza virus will contain. We also do not know that FluMist will be able to generate a vaccine for the pandemic virus.

Currently reads: Vaccination is a cost-effective counter-measure to the threat of seasonal or pandemic outbreaks of influenza.

I suggest: Vaccination is a cost-effective counter-measure to the threat of seasonal outbreaks of influenza, and may also prove applicable in an influenza pandemic.

The exact wording is not important, but making an absolute statement like, "FluMist can save you from the pandemic flu" is fallacious. Nackee (talk) 23:02, 3 March 2008 (UTC)

The nuanced edit suggested above is a good one, because it recognizes studies suggesting that FluMist MAY protect from pandemic H5N1, that protection will remain unproven until an actual pandemic breaks out.

Review of patient ages and outcomes reveals that H5N1 attacks are especially lethal in pre-adults and young adults, while older victims tend to have milder attacks and to survive. ^[1][2][3] Very few persons over 50 years of age died after suffering an H5N1 attack. Instead, the age-fatality curve of H5N1 influenza attacks in humans resembles that of the 1918 Spanish pandemic flu. One factor may be that H1N1 was the predominate human flu circulating from 1918 until 1957 when the H2N2 strain emerged.^[4] Hence those over 50 years old have had the opportunity to be exposed to H1N1, and to develop some immune response to the N1 group contained in that human form of flu. Likewise, annual flu vaccination includes inoculation against a type-A human H1N1 flu, leading to the possibility that the annual flu shot or Flumist inoculation might confer some immunity against H5N1 bird flu infection, and indeed testing the blood of volunteers to look for immune response to H5N1 found that some blood samples showed immunity, but more of the blood samples of persons who had received the flu shot showed an immune response.^[5]

Can someone take a picture of any nasal spray near someone's nose and upload it to commons.wikimedia.org? That way we can use it as an image on this article. Something similar to: http://www.umm.edu/features/images/NasalSpray.jpg   Daniel.Cardenas (talk) 05:24, 11 May 2008 (UTC)

It is basically background information, and lacks the salience of the sections in front of which it has been placed. Other than the HIV information in the final footnote (which belongs in the "from whom recommended" sections, the history section is a footnote. It is out of place intruding itself before the article's currently-applicable information. Perhaps it could be moved to a "history of flumist" article for those few interested in that topic. —Preceding unsigned comment added by 68.166.205.33 (talk) 22:07, 14 January 2009 (UTC)

MedImmune's live attenuated influenza vaccine (LAIV) technology may be particularly well-suited for vaccinating against emerging influenza strains. LAIV is different from the injectable influenza vaccine ("flu shot") in that it is a gentle mist sprayed into the nose, where the influenza virus usually enters the body. It contains live vaccine virus strains that are weakened so as not to cause the flu, but prompt the body to mount an immune response after the first dose. Because it is live and stimulates a broad range of immune responses, LAIV may offer some cross-protection against circulating flu strains that are "drifted" - meaning they are very closely-related but not perfectly matched to the flu strains in the vaccine. —Preceding unsigned comment added by 64.105.0.126 (talk) 00:18, 17 June 2009 (UTC)

"Robert Roos * News Editor

Sep 29, 2009 (CIDRAP News) – While there is evidence that the live nasal-spray vaccine for seasonal influenza works better than injectable vaccine in children, the injectable vaccine was found to be more effective in a trial in close to 2,000 young adults, according to a recent report in the New England Journal of Medicine.

... "

http://www.cidrap.umn.edu/cidrap/content/influenza/swineflu/news/sep2909flumist-jw.html —Preceding unsigned comment added by 66.167.95.156 (talk) 20:44, 6 October 2009 (UTC)

• People less than 6 months of age (before 2010, was 2 years of age^[1]

Many other examples of need to update. —Preceding unsigned comment added by Ocdncntx (talk • contribs) 17:38, 6 November 2010 (UTC)

How is the virus "attenuated"? Is this simply a genetically engineered virus that is designed to have attributes of three other strains, and not cause disease? -- Beland (talk) 22:39, 9 August 2011 (UTC)

Sorry for the late answer, just read your question now. There are three phenotypes that were achieved in the parent strains: ca (cold adaptated), replicating well at 25 degrees Celsius; ts (temperature sensitive), restricting the replication at 37 degrees Celsius, and att (attenuated), not causing classical illness in the ferret model. The parent strains that have these adaptations are incubated with wild type strains with the desired antigens, and this produces genetically reassorted cold adapted strains. These reassortant strains have the ca, ts, and att gene segments from the parent strain, as well gene segments encoding the hemagglutinin and neuraminidase surface proteins from the wild-type virus selected for that year. See: http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4292B1-02.pdf --Synaptophysin (talk) 14:15, 27 August 2013 (UTC)

Thanks, that was very helpful! I just added that material into the new section "Production". -- Beland (talk) 17:25, 5 May 2019 (UTC)

I think the article "FluMist" should be merged into "Live attenuated influenza vaccine". In practice, that would mean moving the content from the "LAIV" article into "FluMist", followed by renaming the latter. I suggest this renaming because the two articles pretty much overlap completely in scope. The reason why I think the single, merged article should be named "Live attenuated influenza vaccine" rather than "FluMist" is because the latter is a brand name, whereas the former is a more generic description. While brand names are appropriate article titles for vaccines (per MOS:MED), I think the generic name should be preferred in this case. A superficial glance of the scientific literature (via www.pubmed.gov) seems to indicate that the generic name is fairly well established. Gabbe (talk) 20:39, 22 December 2012 (UTC)

Since there have been no objections poster here during the last week, I plan to go ahead with the merger. Gabbe (talk) 18:47, 29 December 2012 (UTC)

Included in the product INFORMATION/MONOGRAM, for FluMist - Quadrivalent (Influenza Vaccine Live, Intranasal) Intranasal Spray Vaccine, and under the section titled; "FULL PRESCRIBING INFORMATION: CONTENTS*" - there appears to be information that is missing, and or, intentionally deleted - perhaps they just cant count, sequentially. They do give a reason why items 9 & 10 are missing however: "*Sections or subsections omitted from the full prescribing information are not listed." - This is my point - items 9 & 10 are not being listed - why?

Here is the link to 'their' "FULL PRESCRIBING INFORMATION: CONTENTS*" - or not so full: http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM294307.pdf — Preceding unsigned comment added by NecktopPC (talk • contribs)

@NecktopPC: I moved the above question from the article page, where it was apparently unintentionally posted instead of here. I'm not sure what the answer to your question is. I would assume that this is simply a standard format to which certain sections don't apply. Perhaps they are not useful to prescribing doctors and patients and this is excerpted from a larger document, or perhaps they are simply not applicable to this medication. If you want to find out for sure, I would try finding similar documents and comparing, or contacting the author of the document. -- Beland (talk) 17:48, 27 August 2013 (UTC)

I was also moving this here, and got an edit conflict. @NecktopPC: Whenever any of the sections of the Full Product Information are omitted, the FDA requires the heading "Full Prescribing Information: Contents" be followed by an asterisk and the following statement must appear at the end of the Contents:

• Sections or subsections omitted from the full prescribing in formation are not listed

It is quite common for sections to be omitted, as they may not be applicable to that drug. For example, sections 9 and 10, which are omitted here, are regarding Drug Abuse and Dependence and Overdosage, respectively. As there is no risk of either of these for vaccines, they are typically omitted - vaccines are not addictive and produce no drug dependencies, and it would be difficult to overdose on them. Hopefully this allays your concerns. Further information on labeling can be found in the document Guidance for Industry Labeling for Human Prescription Drug and Biological Products – Implementing the PLR Content and Format Requirements --Synaptophysin (talk) 17:56, 27 August 2013 (UTC)

It would be very helpful if someone could post information about the release date for flumist, especially for this year (2015). All arguments about the relative efficacy of the shot vs flumist go out the window if the shot is available well before flumist, as appears to be the case here in Hawaii in 2015. (The supermarkets are giving out the shot, but no one and no web page seems to be able to tell me when flumist will even arrive.)

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