INFLUENZA VACCINES: THE DIFFICULTY IN PREPARATION

PRESENTED BY:DR RANI KOMAL LATA

MPH 2015-17( 2ND SEM)1

Amity Institute of Virology and Immunology

Influenza, commonly known as ‘the flu’ Serious contagious respiratory illness that

is caused by influenza viruses It can cause mild to severe illness and at

times, can result in hospitalization or death.

Some people, such as older people, young children, and people with certain health conditions, are at high risk for serious flu complications.

INFLUENZA: THE DISEASE

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Single-stranded RNA virus : Orthomyxoviridae family 3 types: A, B, C Subtypes of type A determined by : hemagglutinin and neuraminidase Influenza Virus Strains : TYPE A: moderate to severe illness all age groups humans and other animals TYPE B milder disease primarily affects children & humans only TYPE C rarely reported in humans no epidemics

INFLUENZA VIRUS

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NOMENCLATURE OF THE VIRUS

The name “influenza” originated in 15th century Italy, from an epidemic attributed to “influence of the stars.”

First pandemic in 1580 At least 4 pandemics in 19th century Estimated 21 million deaths worldwide in

pandemic of 1918-1919 Virus first isolated in 1933

EPIDEMIOLOGY

5 www.cdc.gov/flu

1. 1918-19 “Spanish flu” H1N1 2. 1957 “Asian flu” H2N2 3. 1968 “Hong Kong flu” H3N2 4. 1976 “Swine flu” episode H1N1 5. 1977 “Russian flu” H1N1 6. 1997 “Bird flu” in HK H5N1 7. 1999 “Bird flu” in HK H9N2 8. 2003 “Bird flu” in Netherlands H7N7 9. 2004 “Bird flu” in SE Asia H5N1

Pandemics And Pandemic Threats Of The 20th Century

6www.flu.gov/pandemic/history/

The number of influenza associated deaths varies substantially by: year, influenza virus type and subtype, and age group

Annual influenza associated deaths ranged from 3,349 (1985-86 season) to 48,614 (2003-04 season), with an average of 23,607 annual deaths

Persons 65 years of age and older account for approximately 90% of deaths

2.7 times more deaths occurred during seasons when A(H3N2) viruses were prominent

IMPACT OF INFLUENZA-UNITED STATES, (1976-2007)

7 “The Economic Impact of Pandemic Influenza in the United States”

Inactivated subunit (IIV) : intramuscular or intradermal Live attenuated vaccine (LAIV) : intranasal Trivalent vaccine : contains three inactivated viruses:1. Type A(H1N1)2. Type A(H3N2)3. Type B

Quadrivalent influenza vaccines: introduced for the 2013-2014 season. contain the same antigens as trivalent vaccines with the exception that quadrivalent vaccines contain two type B

strains. Vaccine viruses are grown in chicken eggs, and the final product

contains residual egg protein. The vaccine is available in both pediatric (0.25-mL dose) and

adult (0.5-mL dose) formulations.

INFLUENZA VACCINES

8 www.cdc.gov/vaccines

One vaccine contains multiple inactive strains of the virus.

Once administered, the human immune system builds antibodies that recognize these dead flu strains.

That way when the active flu virus enters the body, the immune system is able to recognize the invader and defend itself

Flu vaccines cause humoral antibodies levels to develop in the body about two weeks after vaccination.

These antibodies provide protection against infection with the viruses that are in the vaccine.

HOW FLU VACCINES WORK

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The two most important structural proteins demonstrating genetic and antigenic variation which are relevant to protection and vaccination are the envelope glycoproteins, “the haemagglutinin (HA) and the neuraminidase (NA)”.

HA is particularly important: as it mediates virus attachment to the host cell and antibody induced against the HA neutralises virus infectivity.

The NA is involved in elution of virus from cells and the spread of infection between cells

ANTIGENIC VARIATION OF INFLUENZA VIRUSES INFECTION

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INFLUENZA VIRUSES EVADE HOST IMMUNE RESPONSE

THEY EVOLVE TWO DIFFERENT MECHANISMS TO GENERATE ANTIGENIC VARIATION

CHANGED SURFACE ANTIGENS ESCAPE HOST IMMUNE REPONSE

ANTIGENIC VARIATION(CONT.)

It is a mechanism for variation in viruses that involves the accumulation of mutations within the genes that code for antibody-binding sites.

This results in a new strain of virus particles which cannot be inhibited as effectively by the antibodies that were originally targeted against previous strains.

Viruses that are closely related to each other usually share the same antigenic properties and an immune system exposed to an similar virus will usually recognize it and respond, sometimes called cross-protection.

But these small genetic changes can accumulate over time and result in viruses that are antigenically different (When this happens, the body’s immune system may not recognize those viruses)

Genetic changes that result in a virus with different antigenic properties is the main reason why people can get the flu more than one time.

“ANTIGENIC DRIFT”

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It is the process by which two or more different strains of a virus, or strains of two or more different viruses, combine to form a new subtype having a mixture of the surface antigens of the two or more original strains. This is a specific case of reassortment.

An abrupt, major change in the influenza A viruses, resulting in new hemagglutinin and/or new hemagglutinin and neuraminidase proteins in influenza viruses that infect humans.

Such a “shift” occurred in the spring of 2009, when an H1N1 virus with a new combination of genes emerged to infect people and quickly spread, causing a pandemic.

When shift happens, most people have little or no protection against the new virus.

ANTIGENIC SHIFT

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Understanding the genetic diversity of viral pathogens and how it is modulated by host immunity, transmission, epidemic dynamics and population structures is essential for the development of effective control measures.

Effective vaccination against such viruses requires surveillance programmes to monitor circulating serotypes and their evolution to ensure that vaccine strains match field viruses.

CONCLUSION

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