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Influenza Vaccines

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Contents

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
  • 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.
  • Virus grown in cells – Experimental


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 WHO[3]

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.


References

  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


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


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]

Related Videos

Vaccine Development and a Universal Flu Vaccine

In this video from BigThink, James Merson, Chief Scientific Officer of the Vaccines Research Unit at Pfizer, discusses how vaccines are made, and stresses the importance of developing a universal vaccine for Influenza:

The Barriers to a Global H1N1 Vaccine

As plans for an H1N1 vaccine are announced, Barry Bloom, Professor of Public Health at Harvard, explains the elements of corporate and international policy that will prevent these vaccines from reaching many of the populations that will need them most.


Preventing Pandemics Through Healthcare Reform

Jeffrey Koplan, former head of the CDC and Vice President for Global Health at Emory University, discusses the vital importance of a healthcare reform that provides some level of universal coverage to people and encourages them to come in when theyre sick at early stages in preventing future pandemics:

Preparing for Swine Flu

According to the World Health Organization, The H1N1 Virus is estimated to affect 2 billion people (1/3 of the worlds population) over the next two years. Former head of the CDC, Jeff Koplan discusses the difficulties in preparing for this.


Personal Stories: Why Flu Vaccination Matters

In this video, moving personal stories help inform parents about the dangers of flu to children and the benefits of vaccination.


References

  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.



Seasonal (non-pandemic) flu vaccine links

  • Links about influenza vaccines (not necessarily pandemic flu) from the CDC website
• see also the Flu Wiki discussion of thimerosal in flu vaccines


Chronic illness and flu vaccines


Scientific Publications


News

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