Human Vaccination Against H5N1 Learning objectives Explain the - - PowerPoint PPT Presentation

Human Vaccination Against H5N1

Learning objectives

• Explain the indication for use of seasonal

Influenza vaccination

• Describe seasonal influenza vaccine

composition and matching to circulating influenza strains

• Describe the potential use of pandemic

vaccine to limit spread

• Describe the difference between the use of

vaccine for seasonal epidemics versus pandemics

• Monitor adverse effects of pandemic vaccine

Vaccine composition and selection

Vaccine strain selection

• Annual update of vaccine strains needed due

to antigenic drift of flu viruses

• WHO Global Influenza Surveillance

Programme established in 1948 to coordinate vaccine strain selection activities and recommendations

– Global year-round virologic surveillance – Antigenic and genetic analysis – Serological studies

Source: Bridges, PAHO Influenza Epidemiology Course, May 11, 2005.

WHO collaborating labs

Two main types of vaccines

• Inactivated
• Live, attenuated

Both require

– Yearly administration – Revised twice a year based on international virologic surveillance

Strains most commonly grown in eggs, but also in MDCK and Vero cells.

Source: Bridges, PAHO Influenza Epidemiology Course, May 11, 2005.

Influenza vaccine timetable

Source: Bridges, PAHO Influenza Epidemiology Course, May 11, 2005.

Vaccine Effectiveness

• Depends upon match between vaccine strain

and circulating strain

• 70-90% effective in preventing illness in

healthy persons <65 years

• Less effective for illness in elderly, but can

reduce risk for hospitalization and death

• Reduced vaccine effectiveness if

predominant strain is antigenically drifted from vaccine strain

Influenza vaccine: number of changes 1968-2002

Source: Bridges, PAHO Influenza Epidemiology Course, May 11, 2005.

Adverse reactions

Possible adverse reactions from inactivated vaccines include:

• Common and immediate

– Local reactions in young children – Fever – Malaise

• Rare

– Guillain-Barre syndrome in older adults – Facial palsy – Oculorespiratory syndrome

Source: Bridges, PAHO Influenza Epidemiology Course, May 11, 2005.

Live vaccines are recommended only for healthy people aged 5-49. Contraindications for live vaccines:

• Allergy to eggs
• History of Guillain-Barre syndrome
• <18 on long-term aspirin therapy
• Pregnancy in first trimester
• Immunosuppression

Source: Bridges, PAHO Influenza Epidemiology Course, May 11, 2005.

Cold chain management

http://www.who.int/vaccines-access/vacman/coldchain/the_cold_chain_.htm Vaccine manufacturer Vaccine National airport Primary vaccine store Intermediate vaccine store Intermediate vaccine store Health center Health post Recipient Transit storage facilities (2°C-8°C) Cold room (2°C-8°C) and freezer room (-15°C- -25°C) Refrigerators (2°C-8°C) and cold boxes and/or vaccine carries Transportation in refrigerated trucks, cold boxes, and/or vaccine carriers based on need

Seasonal Versus Pandemic Vaccines

Indications for use of seasonal vaccine

Current influenza prevention strategies

• About 50 countries have government funded

national influenza immunization campaigns

• Recommendations vary by country, but

generally involve annual immunization for:

– Individuals of advanced age – Those with pre-existing chronic medical conditions – Those at increased medical risk

Source: Bridges, PAHO Influenza Epidemiology Course, May 11, 2005.

Who should be vaccinated seasonally?

WHO recommendations

• Age

– ≥ 65 or other nationally defined age limit – Residents of institutions for elderly or disabled

• Occupation

– Individuals with regular, frequent contact with high-risk persons (health care workers) – Individuals with frequent contact with at-risk animals (poultry farmers, cullers, etc.)

• Risk Factors

– Chronic conditions (Cardiovascular, Pulmonary, Metabolic, Renal, Immuno-compromised) – Pregnancy – Vulnerable population (Refugee, migrant, disaster victims)

Source: Bridges, PAHO Influenza Epidemiology Course, May 11, 2005.

Vaccination of children

• Children spread flu quickly due to

– High attack rates – Prolonged shedding – Higher excretion of virus

• The presence of a child is a risk factor for flu

infection in adults (Frank et al 1985)

• Immunization of 85% of school children effective in

reducing severity of community outbreak in influenza A (Tecumseh, Monto, et al, 1970)

• Vaccination in children may protect high-risk adults

Age recommendations in 56 countries, 2003

Source: Bridges, PAHO Influenza Epidemiology Course, May 11, 2005.

Recommendations for high-risk conditions in 56 countries, 2003

Source: Bridges, PAHO Influenza Epidemiology Course, May 11, 2005.

Recommendations for target groups in 56 countries, 2003

Source: Bridges, PAHO Influenza Epidemiology Course, May 11, 2005.

Seasonal vaccination may not be a priority

• Limited data on flu occurrence and

chronic diseases

• Limited health care facilities and

resources

• Other unmet health needs which take

priority

Vaccine Priorities: Seasonal vs Pandemic Influenza

Seasonal

• Annually recommend

vaccination for groups at high risk for severe illness & death, their close contacts, persons 50-64 years old, and HCWs

• High risk includes persons

>65 years, children 6-23 months; persons with underlying chronic disease; and pregnant women

Pandemic

• Initial vaccine supply will be

much more limited

• A pandemic may have

impacts on functioning of the health care system and

• ther essential services

Use of vaccines in a pandemic

• First line of defense in a pandemic to

reduce morbidity and mortality

• Contain virus close to the source

However…

• Last 3 flu pandemics reached the world in 6-9

months—will spread more quickly now due to the shrinking globe

• Takes approximately 4-8 months to formulate

and produce vaccine

• Production capabilities (100 million) are well

short of what is needed

• Vaccine not likely to be available before 2010

http://news.bbc.co.uk/1/hi/sci/tech/5132910.stm

Effectiveness of a pandemic vaccine may not be known until the pandemic has passed.

Goals of the Pandemic Influenza Vaccination

In the likely event of a shortage given current influenza vaccine production capacity, goals of the vaccination program are to:

• Decrease pandemic health impacts
• Preserve critical infrastructure and

minimize societal disruption

Pandemic Vaccine Purchase and Distribution

• Issues to consider

– Need to have manufacturers shift from annual to pandemic vaccine – Incentives for full-scale pandemic vaccine production – Local health department preferences & planning needs – Ability to effectively target doses when short supply – Equity

• Plan recommends that public sector vaccine will be

distributed to States for further distribution/administration

• Payment or reimbursement

Vaccine Prioritization: who is vaccinated first?

• Varies for each country
• Plan in order to simplify the process
• Example of US HHS priority recommendations

WHO does not recommend mass vaccination at this time based on available data.

Vaccine Prioritization Considerations

• Impact on risk of hospitalization. & death based on

data from past pandemics and inter-pandemic influenza

• Likelihood of response to vaccination

(i.e., immunocompromised don’t respond well)

• Anticipated impact of pandemic influenza on demand

for healthcare and critical infrastructure, such as vaccinators and vaccine manufacturers

• Current vaccine production capacity/availability
• Size of prioritized groups

Example:

Pandemic flu vaccine plan for United States

Recommended Vaccine Target Groups-1

Tier Group Population Percent 1A 1A 1B 1B 1B Vaccine, antiviral workers Health care and public health workers w. direct patient contact 40,000 .01% >65 years with >1 high risk condition* 3% 8-9 M 18.2 M 6 mos-64 yrs with >2 high risk conditions 6.9 M 2.3% >6 mos w. history pneumonia/influenza hospitalization 740,000 6.1% 0.2%

* nursing home residents excluded; see http://www.hhs.gov/pandemicflu/plan/appendixd.html

Recommended Vaccine Target Groups-2

Tier Group Population Percent 1C 1C 1C 1D 1D Pregnant women Household contacts of severely immunocompromised persons* 3.0 M 1% Household contacts of children <6 mos 0.9% 2.7 M 5.0 M Public health emergency response workers 150,000 .05% Key government leaders To be determined 1.7% To be determined

* immunocompromised persons excluded; see http://www.hhs.gov/pandemicflu/plan/appendixd.html

Recommended Vaccine Target Groups-3

Tier Group Population Percent 2A 2B 3 4 Other persons at risk, all ages Other responders: public health, public safety, utility, transportation, telecommunications, IT 59.1 M 19.9% 2.9% 8.5 M To be determined plus 62,000 Healthy persons not included above 179.3 M <1% 60.4% Other key government personnel, funeral directors and personnel

For more information, see http://www.hhs.gov/pandemicflu/plan/appendixd.html

Process for monitoring for adverse reactions in a pandemic

With a more widespread use of a vaccine, problems and reactions are likely to be developed that haven’t been seen before.

– Enhanced reporting system – Enhanced surveillance

Current status of vaccine development

• Currently, worldwide production capability is

limited to 300 million influenza vaccines

• Production capabilities at 100 million with

potential AI vaccines over 6 months

• “Once a pandemic has been declared, all

manufacturers would stop production of seasonal vaccines and produce only the pandemic vaccine.” (WHO, Aug 2005)

This is not adequate to protect against a worldwide pandemic

http://news.bbc.co.uk/1/hi/sci/tech/5132910.stm

Development of H5N1 Vaccine

• Current reference virus formulated

through reverse genetics

• Human trials began in April, 2005 vs

H5N1

• Vaccine also being developed against

H9N2

Selected trial results

• GSK announced that trials on their pandemic

flu H5N1 vaccine showed a strong immune response in 80% of subjects with 3.8 µg of antigen (www.gsk.com, July 26, 2006)

• sanofi pasteur found an immune response of

66.7% seroconversion rate after two vaccinations of alum-adjuvanted 30 µg doses in French trials (www.sanofipasteur.com, May 11, 2006)

• sanofi pasteur recorded a 54% response in

US trials after two 90 µg doses

Pandemic Vaccine Supply

• Assumptions

– Imported vaccine will not be available – Two doses (15 ug or more) will be needed for protection – 4-8 months until first vaccine doses available

• Manufacturing capacity

– Inactivated vaccine

• Only sanofi has a completely domestic supply chain
• Estimated production sufficient to deliver ~3-5 million

monovalent doses/week – Live attenuated vaccine

• Bulk produced in the UK
• Production capacity ~1.5 million doses/week

(optimistically)

Human vaccine trials in progress

Sponsor Composition Phase Start date

NIAID Live virus I June 2006 CSL Limited II June 2006 GSK Split virus III May 2006 NIAID Aluminum hydroxide (Chiron) I Feb 2006 NIAID Inactivated Influenza A/H5N1 Vaccine (sanofi pasteur) II Feb 2006 Source: www.clinicaltrials.gov

Summary

• Influenza vaccine composition changes every year

based on the strains of the previous years

• Each country has its own guidelines for seasonal

vaccination, but includes those who are likely to be hospitalized or die due to flu

• A pandemic vaccine could limit spread if it were

available and able to be manufactured quickly

• Vaccines for seasonal epidemics versus pandemics

have different targets and different intentions

• Pandemic vaccine will need surveillance for adverse

effects