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Types of possible flu vaccines

  • Inactivated Influenza Vaccine
    The vast majority of flu vaccines are made this way. Flu virus is grown in chicken eggs and then killed. Production takes 6–9 months
    • Flu Shot Q&A
      CDC, 7 Sep 2005
    • Key Facts about Influenza and the Influenza Vaccine
      CDC, 28 Sep 2005
    • H5N1 Avian Flu Vaccine Trials Q&A
      NIAID, 4 Apr 2005
    • NIAID Initiates Trial of Experimental Avian Flu Vaccine
      NIAID press release, 23 Mar 2005
    • FluShot Locator
      American Lung Association
      More complete information about flu shots in your area is available from you local Department of Health
    • FluSTAR tracks the spread of the flu and provides reports by zip US code
      Roche Laboratories
  • Adjuvants
    • Overview of adjuvants “Compared to injection of antigen alone, injection of antigen plus an adjuvant generally permits use of a much smaller quantity of the antigen and greatly enhances the antibody titer”
  • Live Attenuated Influenza Vaccine (LAIV)
    A relatively new method. A weakened strain of flu virus is grown in chicken eggs. Live virus is sprayed into the nose. This weakened virus is considered safe for healthy people ages 5–49. Production takes 6–9 months.
    • Q&A: The Nasal-Spray (LAIV) Flu Vaccine
      CDC, 13 Sep 2005
  • Virus grown in cells – Experimental
    • Momentum builds for cell-culture flu vaccines
      CIDRAP, 27 June 2005
    • Insect Cells
      Influenza vaccine uses insect cells to speed development
      Eurekalert, 21 Mar 2005
    • Mammalian cells – Experimental
      HHS Awards $97 Million Contract to Develop Cell Culture-Based Influenza Vaccine – “Effort Designed to Diversify and Accelerate Vaccine Production to Enhance Pandemic Preparedness”
      HHS press release, 1 April 2005
  • DNA – Experimental. Can be prepared within 1–2 months.
    Vaccine Against H5N1 (Avian Influenza) Manufactured For Clinical Development
    Medical News Today, 1 Aug 2005
  • Adenovirus vector – Experimental. Could be rapidly scaled up.
    U.S. Researchers Make Progress on Bird Flu Vaccine
    US State Department press release, 13 Sep 2005
  • Key Facts About Flu Vaccine from the CDC. September 7, 2005
  • See also the Flu Wiki page on Vaccine manufacturers

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H5N1 Vaccine Development

Avian Influenza (Bird Flu): Vaccine Development
  • Bird Flu Vaccines from Mayo Clinic 11/05
  • excerpt from CIDRAP’s avian influenza overview (updated continuously)

Because of concerns about the pandemic potential of H5N1, WHO has been working with laboratories in the WHO influenza network to develop vaccines against this subtype.1

  • Candidate vaccines were developed during 2003 by network laboratories in London and in Memphis, Tennessee, for protection against the strain that was isolated from humans in Hong Kong in February of that year. However, the 2004 strain is different from that strain.
  • In April 2004, WHO made the prototype seed strain for an H5N1 vaccine available to manufacturers.2
  • The National Institute of Allergy and Infectious Diseases (NIAID) awarded two contracts to support the production and clinical testing of an investigational vaccine based on the prototype seed strain made available by WHO3

At this point, it is not clear if prototype H5 vaccines will offer protection against an emergent pandemic strain. Research in this area is a high priority because stockpiling prototype vaccines may be worthwhile if protection against emergent strains can be demonstrated.4

  • One recent study demonstrated good cross-protection against H5N1 in mice following vaccination with an H5 influenza vaccine created through reverse genetics.5 Protection was achieved despite antigenic differences and incomplete matching between the vaccine strain and the challenge virus. Although these findings are promising, it is not clear if similar protection would occur for humans.
  • A second study suggested that use of adjuvanted prototype vaccines may induce antibody capable of neutralizing a pandemic strain until a well-matched vaccine can be made available. In the study, 14 human subjects vaccinated with an adjuvanted influenza A/duck/Singapore 97 (H5N3) vaccine demonstrated higher seroconversion rates to four strains of H5N1 compared with 11 subjects who were vaccinated with a nonadjuvanted vaccine.6 For those who received the MF59-adjuvanted vaccine, 100% seroconverted to A/HongKong/156/97 and A/HongKong/213/03, 71% to A/Thailand/16/04, and 43% to A/Vietnam/1203/04.

One way of protecting against all types of influenza, including emerging pandemic strains, would be a universal flu vaccine that would not have to be reengineered each year. The British company Acambis announced in early August 2005 that it is developing such a vaccine and has had successful results in animal testing.7 The vaccine would focus on the M2 viral protein, which does not change, rather than the surface hemagglutinin and neuraminidase proteins targeted by traditional vaccines. The universal vaccine is made through bacterial fermentation technology, which would greatly speed up the rate of production over that possible with culture in chicken eggs, plus the vaccine could be produced continuously, since its formulation would not change. Still, such a vaccine is years away from full testing, approval, and use. Other researchers are also working on a universal agent.


1 see WHO: Status of vaccine development for an influenza pandemic, 4 Oct 2005 (↑)

2 see WHO: Situation in Thailand, 4 Oct 2005 (↑)

3 see NIAID: Press release, May 2004 (↑)

4 see Schwartz B, Gellin B. Vaccination strategies for an influenza pandemic. (Commentary) J Infect Dis 2005 Apr 15;191:1207–9. (↑)

5 see Lipotov AS, Webby RJ, Govorkova EA, et al. Efficacy of H5 influenza vaccines produced by reverse genetics in a lethal mouse model. J Infect Dis 2005 Apr 15;191:1216–20 Abstract (↑)

6 see Stephenson I, Bugarini R, Nicholson KG, et al. Cross-reactivity to highly pathogenic avian influenza H5N1 viruses after vaccination with nonadjuvanted and MF59-adjuvanted influenza A/duck/Singapore/97 (H5N3) vaccine: a potential priming strategy. J Infect Dis 2005 Apr 15;191:1210–5 Abstract (↑)

7 see Acambis press release , 4 Aug 2005 (↑)

  • Pandemic Influenza Vaccine Research and Development (powerpoint format)
    Presentation by Linda C. Lambert at the National Vaccine Advisory Committee, June 7 2005

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Rationing of vaccine in the likely event of a shortage

  • See Vaccines and rationing in the Ethics section
  • Tiered Use of Inactivated Influenza Vaccine in the Event of a Vaccine Shortage
    CDC vaccine rationing plan
  • Prioritization of Healthcare Worker Vaccination (powerpoint format)
    Presentation by the Pandemic Influenza Working Group on June 15, 2005

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Pregnant Women

Pregnancy and the Flu Shot

Source: Summary from the Palo Alto Medical Foundation

Pregnant women — especially those in late pregnancy — are at risk for complications from influenza, or “the flu,” even if they are healthy. The most thorough study of influenza-related illness during pregnancy was reported in 1998.1 This study examined the effect of the flu on pregnant women during 17 previous influenza seasons.

The study found that during the flu season pregnant women in the third trimester were just as likely to be hospitalized for heart or lung problems as women with serious, chronic medical conditions who were not pregnant. The risk increased the farther along the pregnancy. Healthy women at 37–42 weeks gestation were almost 5 times as likely to be admitted to the hospital during the flu season for heart or lung problems as women who were 1–6 months post-partum.

Pregnant women with asthma were particularly at risk for hospitalization during the flu season.2 Will the flu shot help? It is reasonable to believe that the flu shot will provide protection to pregnant women as it does in seniors although no controlled studies are yet available to confirm this.

Information Regarding Vaccination of Specific Populations – Pregnant Women

excerpt from Prevention and Control of Influenza, Morbidity and Mortality Weekly Report 54(Early Release);1–40. 13 July 2005

Influenza-associated excess deaths among pregnant women were documented during the pandemics of 1918-−19 and 1957-−58.3 Case reports and limited studies also indicate that pregnancy can increase the risk for serious medical complications of influenza.4 An increased risk might result from 1) increases in heart rate, stroke volume, and oxygen consumption; 2) decreases in lung capacity; and 3) changes in immunologic function during pregnancy. A study of the effect of influenza during 17 interpandemic influenza seasons demonstrated that the relative risk for hospitalization for selected cardiorespiratory conditions among pregnant women enrolled in Medicaid increased from 1.4 during weeks 14-−20 of gestation to 4.7 during weeks 37-−42, in comparison with women who were 1-−6 months postpartum. 5 Women in their third trimester of pregnancy were hospitalized at a rate (i.e., 250/100,000 pregnant women) comparable with that of nonpregnant women who had high-risk medical conditions. Researchers estimate that an average of 1-−2 hospitalizations can be prevented for every 1,000 pregnant women vaccinated.6

Because of the increased risk for influenza-related complications, women who will be pregnant during the influenza season should be vaccinated. Vaccination can occur in any trimester. One study of influenza vaccination of approximately 2,000 pregnant women demonstrated no adverse fetal effects associated with influenza vaccine.7


1 Neuzil KM, Reed GW, Mitchel EF, Simonsen L, Griffin MR. Impact of influenza on acute cardiopulmonary hospitalizations in pregnant women. Am J Epidemiol 1998; 148:1094–102. (↑)

2 Hartert T, Neuzil K, Shintani A, Mitchel E, Snowden M, Wood L, Dittus R, Griffin M. Maternal morbidity and perinatal outcomes among pregnant women with respiratory hospitalizations during influenza season. Am J Obstet Gynecol 2003;189:1705–12. (↑)

3 Noble G. Epidemiological and clinical aspects of influenza. In: Beare AS, ed. Basic and applied influenza research. Boca Raton, FL: CRC Press; 1982:11-−50.
Harris JW. Influenza occurring pregnant women: a statistical study of thirteen hundred and fifty cases. JAMA 1919;72:978-−80.
Widelock D, Csizmas L, Klein S. Influenza, pregnancy, and fetal outcome. Public Health Rep 1963;78:1-−11.
Freeman DW, Barno A. Deaths from Asian influenza associated with pregnancy. Am J Obstet Gynecol 1959;78:1172-−5. (↑)

4 Shahab SZ, Glezen WP. Influenza virus. In: Gonik B, ed. Viral diseases in pregnancy. New York, NY: Springer-Verlag; 1994:215-−23.
Schoenbaum SC, Weinstein L. Respiratory infection in pregnancy. Clin Obstet Gynecol 1979;22:293-−300.
Kirshon B, Faro S, Zurawin RK, et al. Favorable outcome after treatment with amantadine and ribavirin in a pregnancy complicated by influenza pneumonia. A case report. J Reprod Med 1988;33:399-−401.
Kort BA, Cefalo RC, Baker VV. Fatal influenza A pneumonia in pregnancy. Am J Perinatol 1986;3:179-−82.
Irving WL, James DK, Stephenson T, et al. Influenza virus infection in the second and third trimesters of pregnancy: a clinical and seroepidemiological study. BJOG 2000;107:1282-−9. (↑)

5 Neuzil KM, Reed GW, Mitchel EF, et al. Impact of influenza on acute cardiopulmonary hospitalizations in pregnant women. Am J Epidemiol 1998;148:1094-−102. (↑)

6 Neuzil KM, Reed GW, Mitchel EF, et al. Impact of influenza on acute cardiopulmonary hospitalizations in pregnant women. Am J Epidemiol 1998;148:1094-−102. (↑)

7 Heinonen OP, Shapiro S, Monson RR, et al. Immunization during pregnancy against poliomyelitis and influenza in relation to childhood malignancy. Int J Epidemiol 1973;2:229-−35. (↑)

  • Influenza vaccination of women during pregnancy WHO statement
  • Q&A: Thimerosal-containing influenza vaccine
    from the CDC’s website; includes statement on flu vaccine safety during pregnancy
  • MMWR - Prevention and Control of Influenza
    CDC’s Morbidity and Mortality Weekly Report 54(Early Release);1–40. 13 July 2005
  • Does Influenza Vaccinaton of Pregnant Mothers Protect Infants Aged <6 Months? (powerpoint format)
    Presentation by Iwane et al. at the Pandemic Flu Working group, June 15 2005-]
  • Flu and Pregnancy from the March of Dimes
  • Pregnancy and the Flu Shot summary from the Palo Alto Medical Foundation

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Seasonal (non-pandemic) flu vaccine links

  • Links about influenza vaccines (not necessarily pandemic flu) from the CDC website
    • Options for controlling influenza
    • Influenza vaccine pre-booking
      and distribution strategies for the 2005-2006 influenza season
    • Q & A: Thimerosal-containing influenza vaccine
      • see also the Flu Wiki discussion of thimerosal in flu vaccines
    • Prevention and control of influenza:
      Recommendations of the advisory committee on immunization practices (ACIP)
      added July 2005
    • CDC Guidelines for Large-Scale Influenza Vaccination
      Clinic Planning 2004-05
      (7 pp pdf, 346 KB)
    • Fluwiki discussion on seasonal flu vaccines

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Chronic illness and flu vaccines

  • HIV/AIDS and the Flu from the CDC

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Scientific Publications

  • Prevention and Control of Influenza
    Recommendations of the Advisory Committee on Immunization Practices (ACIP), Harper et al., MMWR, July 2005

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  • Low-dose bird flu vaccine tested on humans
    Sep 15 2005. Sanofi Pasteur’s trial is testing low doses of killed vaccine virus combined with adjuvant - a chemical that stimulates the immune system
  • Positive results of little practical use, experts warn
    Nature Aug 10 2005
  • Bird flu vaccine requires huge doses; stretching strategies critical: experts
    Canadian Press. Aug 9 2005
  • Vaccine for bird flu tests well, but making enough may be problem
    International Herald Tribune. Aug 8 2005
  • Vaccine Appears to Ward Off Bird Flu
    Washington Post. Aug 7 2005
  • Avian Flu Vaccine Called Effective in Human Testing
    NY Times. Aug 6 2005
  • Pandemic Risk Spurs Flu Vaccine Planning
    Washington Post, Nov 1 2004
Page last modified on February 14, 2007, at 01:14 PM by Lisa the GP