Sunday, May 17, 2009

Vaccines & Influenza Vaccine

A vaccine is a biological preparation that establishes or improves immunity to a particular disease. A vaccine typically contains a small amount of an agent that resembles a virus or other microorganism. The agent stimulates the body's immune system to recognize the agent as foreign, destroy it, and "remember" it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters.

The term vaccine derives from Edward Jenner's 1796 use of the term cow pox (Latin variolæ vaccinæ, adapted from the Latin vaccīn-us, from vacca cow), which, when administered to humans, provided them protection against smallpox.


Sometime during the 1770s Edward Jenner heard a milkmaid boast that she would never have the often-fatal or disfiguring disease smallpox, because she had already had cowpox, which has very mild effect in humans. In 1796 Jenner took pus from the hand of a milkmaid with cowpox, inoculated an 8-year-old boy with it, and six weeks later variolated the boy's arm with smallpox, afterwards observing that the boy did not catch smallpox.[1] Since vaccination against smallpox was much safer than smallpox inoculation, the latter fell into disuse and was eventually banned in England in 1849.[citation needed] In 1885, Louis Pasteur generalized Jenner's idea by developing what he called a rabies vaccine (now termed an antitoxin), and in the 19th century vaccines were considered a matter of national prestige, and compulsory vaccination laws were passed.[1]

The 20th century saw the introduction of several successful vaccines, including those against diphtheria, measles, mumps, and rubella. Major achievements included the development of the polio vaccine in the 1950s and the eradication of smallpox during the 1960s and 1970s. As vaccines became more common, many people began taking them for granted. However, vaccines remained elusive for many important diseases, including malaria and HIV.[1]

Influenza Vaccine

The influenza vaccine is an annual vaccine to protect against the highly variable influenza virus. "Influenza vaccination is the most effective method for preventing influenza virus infection and its potentially severe complications."[1][2][3]

An influenza epidemic emerges during each winter's flu season. In the United States alone an estimated 36,000 people die each year from influenza and accompanying opportunistic infections and complications.[4]

The economic costsin the U.S. have been estimated at over $80 Billion.

The number of annual influenza-related hospitalizations is many times the number of deaths.[5]

In Canada, the National Advisory Committee on Immunization, 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 six and 24 months, and their household contacts, should be considered a high priority for the flu vaccine.[7]

In the United States, the CDC recommends to clinicians that

In general, anyone who wants to reduce their chances of getting influenza can get vaccinated. Vaccination is especially important for people at higher risk of serious influenza complications or people who live with or care for people at higher risk for serious complications.[8]

Vaccination against influenza is recommended for most members of high-risk groups who would be likely to suffer complications from influenza. Specific recommendations include all children and teenagers, from six months to 18 years; of age;[7]

In expanding the new upper age limit to 18 years, the aim is to reduce both the time children and parents lose from visits to pediatricians and missing school and the need for antibiotics for complications ...
An added expected benefit would be indirect — to reduce the number of influenza cases among parents and other household members, and possibly spread to the general community.[9]

In the event of exposure to H5N1-type (avian influenza), seasonal flu vaccine may also offer some protection against H5N1 infection.[10][11][12]

Efficacy of vaccine

Flu vaccines are available both as an injection of killed virus (or flu shot) and as nasal spray of live attenuated influenza virus (LAIV) (sold as FluMist in the United States). LAIV is not recommended for individuals under age 2 or over age 50.[13]

Vaccine is effective against influenza, but not perfect. A study led by Dr. David K. Shay in February, 2008 reported that

"full immunization against flu provided about a 75 percent effectiveness rate in preventing hospitalizations from influenza complications in the 2005-6 and 2006-7 influenza seasons."[14]

While no statistically significant advantage emerged for either LAIV or TIV (needle-injected vaccine) over the other in two trials among adults noted by the CDC,

the benefit of influenza vaccination over non-vaccination were clear:

"One randomized, double-blind, placebo-controlled challenge study among 92 healthy adults aged 18–41 years assessed the efficacy of both LAIV and TIV in preventing influenza infection when challenged with wild-type strains that were antigenically similar to vaccine strains. The overall efficacy in preventing laboratory-documented influenza from all three influenza strains combined was 85% and 71%, respectively.

In a randomized, double-blind, placebo-controlled trial, conducted among young adults during an influenza season when the majority of circulating H3N2 viruses were antigenically drifted from that season’s vaccine viruses, the efficacy of LAIV and TIV against culture-confirmed influenza was 57% and 77%, respectively.

The 57-77% efficacy rate of the influenza vaccine is not universal, however. The group most vulnerable to the illness, the elderly, is also the least affected by the vaccine, with an average efficacy rate ranging from 40-50% at age 65, and 15-30% past age 70. [15][16][17] There are multiple reasons behind this steep decline in vaccine efficacy, the most common of which are the declining immunological function and frailty associated with advanced age.[18]

In most years (16 of the 19 years before 2007), the flu vaccine strains have been a good match for the circulating strains.[24] In other flu seasons like that of 2007/2008, the match was less useful. But even a mis-matched vaccine can often provide some protection:

...[A]ntibodies made in response to vaccination with one strain of influenza viruses can provide protection against different, but related strains. A less than ideal match may result in reduced vaccine effectiveness against the variant viruses, but it still can provide enough protection to prevent or lessen illness severity and prevent flu-related complications. In addition, it’s important to remember that the influenza vaccine contains three virus strains so the vaccine can also protect against the other two viruses. For these reasons, even during seasons when there is a less than ideal match, CDC continues to recommend influenza vaccination. This is particularly important for people at high risk for serious flu complications and their close contacts.[25]
Analysis of studies concluded that people over 65 who got flu shots were half as likely to die over the winter as their unvaccinated peers; this has become the consensus view.

However, it has been pointed out that the number of flu deaths among elderly people in the US has remained at around 5% of winter deaths from 1980 until 2005, although vaccination coverage increased from around 15% in 1980 to around 70% in 2005. Also the biggest supposed benefit from the flu shot occurred in the months before the flu season had started.

Influenza History

The first influenza pandemic was recorded in 1580; since this time, various methods have been employed to eradicate its cause.[26] The etiological cause of influenza, the orthomyxoviridae was finally discovered by the Medical Research Council (MRC) of the United Kingdom in 1933.[27]

Known flu pandemics:[28]

  • 1889–90 — Asiatic (Russian) Flu, mortality rate said to be 0.75–1 death per 1000 possibly H2N2
  • 1900 — Possibly H3N8
  • 1918–20 – Spanish Flu, 500 million ill, at least 20–40 million died of H1N1
  • 1957–58 – Asian Flu, 1 to 1.5 million died of H2N2
  • 1968–69 – Hong Kong Flu, 3/4 to 1 million died of H3N2

Flu vaccine origins and development

In the world wide Spanish flu pandemic of 1918, "Physicians tried everything they knew, everything they had ever heard of, from the ancient art of bleeding patients, to administering oxygen, to developing new vaccines and sera (chiefly against what we now call Hemophilus influenzae—a name derived from the fact that it was originally considered the etiological agent—and several types of pneumococci). Only one therapeutic measure, transfusing blood from recovered patients to new victims, showed any hint of success."[29]

In 1931, viral growth in embryonated hens' eggs was discovered, and in the 1940s, the US military developed the first approved inactivated vaccines for influenza, which were used in the Second World War (Baker 2002, Hilleman 2000). Greater advances were made in vaccinology and immunology, and vaccines became safer and mass-produced. Today, thanks to the advances of molecular technology, we are on the verge of making influenza vaccines through the genetic manipulation of influenza genes (Couch 1997, Hilleman 2002).[30]

Flu vaccine acceptance

According to the CDC: "Influenza vaccination is the primary method for preventing influenza and its severe complications. [...] Vaccination is associated with reductions in influenza-related respiratory illness and physician visits among all age groups, hospitalization and death among persons at high risk, otitis media among children, and work absenteeism among adults. Although influenza vaccination levels increased substantially during the 1990s, further improvements in vaccine coverage levels are needed".[31]

Current status

Influenza research includes molecular virology, molecular evolution, pathogenesis, host immune responses, genomics, and epidemiology. These help in developing influenza countermeasures such as vaccines, therapies and diagnostic tools. Improved influenza countermeasures require basic research on how viruses enter cells, replicate, mutate, evolve into new strains and induce an immune response. The Influenza Genome Sequencing Project is creating a library of influenza sequences that will help us understand what makes one strain more lethal than another, what genetic determinants most affect immunogenicity, and how the virus evolves over time. Solutions to limitations in current vaccine methods are being researched.

Today, we have the capability to produce 300 million doses of trivalent vaccine per year — enough for current epidemics in the Western world, but insufficient for coping with a pandemic.[34]

Various public health organizations have recommended that yearly influenza vaccination be routinely offered to patients at risk of complications of influenza:
  • the elderly (UK recommendation is those aged 65 or above)
  • others at severe risk
In the United States a person aged 50–64 is nearly ten times more likely to die an influenza-associated death than a younger person, and a person over age 65 is over ten times more likely to die an influenza-associated death than the 50–64 age group.[46] Vaccination of those over age 65 reduces influenza-associated death by about 50%.[47][48]

Side effects

Side effects of the inactivated/dead flu vaccine injection are:

  • mild soreness
  • redness
  • death (very rare)[52]
  • swelling where the shot was given
  • fever
  • aches

These problems usually begin soon after the injection, and last 1–2 days.[53]

Side effects of the activated/live/LAIV flu nasal spray vaccine: Some children and adolescents 2–17 years of age have reported mild reactions, including:

  • runny nose, nasal congestion or cough
  • fever
  • headache and muscle aches
  • wheezing
  • abdominal pain or occasional vomiting or diarrhea[54]

Some adults 18–49 years of age have reported:

  • runny nose or nasal congestion
  • sore throat
  • cough, chills, tiredness/weakness
  • headache[54]

Flu vaccine virus selection

Each year, three strains are chosen for selection in that year's flu vaccination by the WHO Global Influenza Surveillance Network. The chosen strains are the H1N1, H3N2, and Type-B strains thought most likely to cause significant human suffering in the coming season.

The Global Influenza Surveillance Network's selection of viruses for the vaccine manufacturing process is based on its best estimate of which strains will be predominant the next year, amounting in the end to well-informed but fallible guesswork.[58]


Vaccines have been formulated against several of the avian H5N1 influenza varieties. Vaccination of poultry against the ongoing H5N1 epizootic is widespread in certain countries. Some vaccines also exist for use in humans, and others are in testing, but none have been made available to civilian populations, nor produced in quantities sufficient to protect more than a tiny fraction of the Earth's population in the event that an H5N1 pandemic breaks out.

Three H5N1 vaccines for humans have been licensed as of June 2008:[62]

All are produced in eggs and would require many months to be altered to a pandemic version.

H5N1 continually mutates, meaning vaccines based on current samples of avian H5N1 cannot be depended upon to work in the case of a future pandemic of H5N1. While there can be some cross-protection against related flu strains, the best protection would be from a vaccine specifically produced for any future pandemic flu virus strain. Dr. Daniel Lucey, co-director of the Biohazardous Threats and Emerging Diseases graduate program at Georgetown University, has made this point, "There is no H5N1 pandemic so there can be no pandemic vaccine." However, "pre-pandemic vaccines" have been created; are being refined and tested; and do have some promise both in furthering research and preparedness for the next pandemic. Vaccine manufacturing companies are being encouraged to increase capacity so that if a pandemic vaccine is needed, facilities will be available for rapid production of large amounts of a vaccine specific to a new pandemic strain.

Problems with H5N1 vaccine production include:

  • lack of overall production capacity
  • lack of surge production capacity (it is impractical to develop a system that depends on hundreds of millions of 11-day old specialized eggs on a standby basis)

Annual reformulation of flu vaccine

Each year the influenza virus changes and different strains become dominant. Due to the high mutation rate of the virus a particular vaccine formulation is effective for at most about a year. The World Health Organization coordinates the contents of the vaccine each year to contain the most likely strains of the virus to attack the next year.

2007–2008 season (Northern Hemisphere)

The composition of influenza virus vaccines for use in the 2007–2008 Northern Hemisphere influenza season recommended by the World Health Organization on February 14, 2007[87] was:

  • an A/Solomon Islands/3/2006 (H1N1)-like virus;
  • an A/Wisconsin/67/2005 (H3N2)-like virus (A/Wisconsin/67/2005 (H3N2) and A/Hiroshima/52/2005 were used at the time);
  • a B/Malaysia/2506/2004-like virus[88][89]

In the US, the CDC reported in Feb 2008 that the H1N1 component was a good match (96%) to the infections occurring. But 87% of the H3N2 are A/Brisbane/10/2007-like viruses, which are a recent antigenic variant of the vaccine strain, A/Wisconsin. And 93% of the B viruses are in a B/Yamagata lineage that is relatively distinct from the vaccine strain B/Victoria lineage. Only one of the three components was a good match; A/Wisconsin is moderately protective against the drifted A/Brisbane strain. 4.5% of those viruses tested are resistant to Oseltamivir, or Tamiflu—a significant increase over previous years.[90]

This vaccine has been described as 40% effective compared to other years that have been 85–95% effective.[91][90]

2008-2009 season (Northern Hemisphere)

The composition of virus vaccines for use in the 2008-2009 Northern Hemisphere influenza season recommended by the World Health Organization on February 14, 2008[94] was:

  • an A/Brisbane/59/2007 (H1N1)-like virus;
  • an A/Brisbane/10/2007 (H3N2)-like virus (A/Brisbane/10/2007 was used at the time);
  • a B/Florida/4/2006-like virus (B/Florida/4/2006 and B/Brisbane/3/2007 (a B/Florida/4/2006-like virus) were used at the time).[95][96]

2009-2010 season (Northern Hemisphere)

The composition of virus vaccines for use in the 2009-2010 Northern Hemisphere influenza season recommended by the World Health Organization on February 12, 2009[99] was:

  • an A/Brisbane/59/2007 (H1N1)-like virus;
  • an A/Brisbane/10/2007 (H3N2)-like virus;
  • a B/Brisbane/60/2008-like virus.[100][101]


In 2004, Influenzavirus A subtype H3N8 was discovered to cause canine influenza. Because of the lack of previous exposure to this virus, dogs have no natural immunity to this virus. There is no vaccine available at this time, but there has been investigation of a canarypox-vectored vaccine for equine influenza virus for use in dogs.[110]

Colds and flu advice from NHS Direct

About the Flu Jab

Flu is a highly infectious illness which spreads very rapidly through coughs and sneezes of people who are already carrying the virus.

Flu vaccination (the flu jab) gives you good protection from flu and lasts for 1 year. The vaccine is normally available in the autumn and is made from the strain of flu that is expected in the coming winter. To stay protected, you need to have a flu jab every year.

See if you are eligible to receive a free flu jab.

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