1. SIGNIFICANT CHALLENGES
FOR AH1N1 VACCINE
DEVELOPMENT:
WILL VACCINES SOLVE
THE PROBLEMS OF
INFLUENZA AH1N1?
Monday, February 6, 2012

2. THE PANDEMIC: April 27, 2009
The emergence of avian influenza A(H5N1) followed by the A(H1N1) influenza pandemic
has focused the attention of the public and health authorities alike on the potential for
prevention using the appropriate vaccines
Monday, February 6, 2012

3. Influenza Life Cycle
Reference:Med. Micro. Murray et al Chapter 56
Monday, February 6, 2012

4. Monday, February 6, 2012

5. Monday, February 6, 2012

6. CO-CIRCULATION WITH SEASONAL
FLU IN 2010
Monday, February 6, 2012

7. UPDATE: SOUTHEAST ASIA
In southeast Asia, transmission of pandemic influenza
virus A(H1N1) persists, but current activity levels are low
Vietnam: influenza activity has declined substantially
since peaking during October and November 2009
Thailand: focal outbreaks of influenza were reported from
a few provinces in northern and central parts of the
country, however, overall ILI activity remains low
Latest available statistic for The Philippines from WHO:
3207 cases with 6 deaths as of 30 July 2009
Monday, February 6, 2012

8. UPDATE: SOUTHEAST ASIA
In southeast Asia, transmission of pandemic influenza
virus A(H1N1) persists, but current activity levels are low
Vietnam: influenza activity has declined substantially
since peaking during October and November 2009
Thailand: focal outbreaks of influenza were reported from
a few provinces in northern and central parts of the
country, however, overall ILI activity remains low
Latest available statistic for The Philippines from WHO:
3207 cases with 6 deaths as of 30 July 2009
Monday, February 6, 2012

9. VACCINATION UPDATE
Monday, February 6, 2012

10. VACCINATION UPDATE
• “CDC recommends influenza vaccination as the first and most important
step in protecting against flu
Monday, February 6, 2012

11. VACCINATION UPDATE
• “CDC recommends influenza vaccination as the first and most important
step in protecting against flu
• CDC is now encouraging everyone to get vaccinated against 2009 H1N1,
including people 65 years and older
Monday, February 6, 2012

12. VACCINATION UPDATE
• “CDC recommends influenza vaccination as the first and most important
step in protecting against flu
• CDC is now encouraging everyone to get vaccinated against 2009 H1N1,
including people 65 years and older
• While less common than with seasonal flu, severe illnesses and deaths
from 2009 H1N1 have occurred in every age group, including people 65
and older
Monday, February 6, 2012

13. VACCINATION UPDATE
• “CDC recommends influenza vaccination as the first and most important
step in protecting against flu
• CDC is now encouraging everyone to get vaccinated against 2009 H1N1,
including people 65 years and older
• While less common than with seasonal flu, severe illnesses and deaths
from 2009 H1N1 have occurred in every age group, including people 65
and older
• Vaccination of people with certain health conditions is especially
important because they are more likely to get serious flu-related
complications
Monday, February 6, 2012

14. VACCINATION UPDATE
• “CDC recommends influenza vaccination as the first and most important
step in protecting against flu
• CDC is now encouraging everyone to get vaccinated against 2009 H1N1,
including people 65 years and older
• While less common than with seasonal flu, severe illnesses and deaths
from 2009 H1N1 have occurred in every age group, including people 65
and older
• Vaccination of people with certain health conditions is especially
important because they are more likely to get serious flu-related
complications
• Health complications that increase the risk of being hospitalized from
2009 H1N1 include:
• Lung disease like asthma or chronic obstructive pulmonary disease
(COPD); Diabetes; Heart disease; Neurological disease; Pregnancy
Monday, February 6, 2012

15. Monday, February 6, 2012

16. Monday, February 6, 2012

17. RECOMMENDATION:
VACCINATION
Monday, February 6, 2012

18. ISSUE: MOCK-UP Mock-up vaccines contain an active ingredient for an
VACCINES influenza virus that has not circulated recently in human
populations and thus mimics the novelty of a pandemic
virus
Such advance studies can greatly expedite regulatory
approval
Monday, February 6, 2012

19. ISSUE: MOCK-UP
VACCINES
Monday, February 6, 2012

20. ISSUE: MOCK-UP
VACCINES
• Mock-up pandemic influenza vaccine:
Monday, February 6, 2012

21. ISSUE: MOCK-UP
VACCINES
• Mock-up pandemic influenza vaccine:
• a vaccine that mimics the future pandemic influenza
vaccine in terms of its composition and manufacturing
method
Monday, February 6, 2012

22. ISSUE: MOCK-UP
VACCINES
• Mock-up pandemic influenza vaccine:
• a vaccine that mimics the future pandemic influenza
vaccine in terms of its composition and manufacturing
method
• NOTE: virus strain causing the pandemic is not known
Monday, February 6, 2012

23. ISSUE: MOCK-UP
VACCINES
• Mock-up pandemic influenza vaccine:
• a vaccine that mimics the future pandemic influenza
vaccine in terms of its composition and manufacturing
method
• NOTE: virus strain causing the pandemic is not known
• mock-up vaccine contains another flu strain instead
Monday, February 6, 2012

24. ISSUE: MOCK-UP
VACCINES
• Mock-up pandemic influenza vaccine:
• a vaccine that mimics the future pandemic influenza
vaccine in terms of its composition and manufacturing
method
• NOTE: virus strain causing the pandemic is not known
• mock-up vaccine contains another flu strain instead
• a strain that is not circulating in humans, and to which
humans have not been exposed in the past
Monday, February 6, 2012

25. ISSUE: MOCK-UP
VACCINES
• Mock-up pandemic influenza vaccine:
• a vaccine that mimics the future pandemic influenza
vaccine in terms of its composition and manufacturing
method
• NOTE: virus strain causing the pandemic is not known
• mock-up vaccine contains another flu strain instead
• a strain that is not circulating in humans, and to which
humans have not been exposed in the past
• test vaccines in preparation for any flu pandemic that may
occur in the future : predict how people will react to the
vaccine when the strain causing a pandemic is included
Monday, February 6, 2012

26. ISSUE: MOCK-UP
VACCINES
Monday, February 6, 2012

27. ISSUE: MOCK-UP
• ISSUES: VACCINES
Monday, February 6, 2012

28. ISSUE: MOCK-UP
• ISSUES: VACCINES
• 1) The viral strain chosen for this mock-up is one that is not currently circulating in
humans. Thus, they are choosing a viral strain to which humans have no acquired
immune defense.
Monday, February 6, 2012

29. ISSUE: MOCK-UP
• ISSUES: VACCINES
• 1) The viral strain chosen for this mock-up is one that is not currently circulating in
humans. Thus, they are choosing a viral strain to which humans have no acquired
immune defense.
• 2) These mock-up vaccines are tested on humans in order to "predict how people
will react."
Monday, February 6, 2012

30. ISSUE: MOCK-UP
• ISSUES: VACCINES
• 1) The viral strain chosen for this mock-up is one that is not currently circulating in
humans. Thus, they are choosing a viral strain to which humans have no acquired
immune defense.
• 2) These mock-up vaccines are tested on humans in order to "predict how people
will react."
• CONSEQUENCES:
Monday, February 6, 2012

31. ISSUE: MOCK-UP
• ISSUES: VACCINES
• 1) The viral strain chosen for this mock-up is one that is not currently circulating in
humans. Thus, they are choosing a viral strain to which humans have no acquired
immune defense.
• 2) These mock-up vaccines are tested on humans in order to "predict how people
will react."
• CONSEQUENCES:
• injecting people with viral fragments that have never been previously encountered
by humans
Monday, February 6, 2012

32. ISSUE: MOCK-UP
• ISSUES: VACCINES
• 1) The viral strain chosen for this mock-up is one that is not currently circulating in
humans. Thus, they are choosing a viral strain to which humans have no acquired
immune defense.
• 2) These mock-up vaccines are tested on humans in order to "predict how people
will react."
• CONSEQUENCES:
• injecting people with viral fragments that have never been previously encountered
by humans
• if mistakes are made in the processing of these vaccines, causing live viruses to be
injected (instead of sufficiently weakened viruses), this could result in the spread
of that new virus among the human population
Monday, February 6, 2012

33. ISSUE: MOCK-UP
• ISSUES: VACCINES
• 1) The viral strain chosen for this mock-up is one that is not currently circulating in
humans. Thus, they are choosing a viral strain to which humans have no acquired
immune defense.
• 2) These mock-up vaccines are tested on humans in order to "predict how people
will react."
• CONSEQUENCES:
• injecting people with viral fragments that have never been previously encountered
by humans
• if mistakes are made in the processing of these vaccines, causing live viruses to be
injected (instead of sufficiently weakened viruses), this could result in the spread
of that new virus among the human population
• this process could be used as vector through which infectious disease is spread
(depends on which virus is chosen for the mock-up vaccines)
Monday, February 6, 2012

34. POSSIBLE MECHANISMS FOR THE
EMERGENCE OF PANDEMIC VIRUSES
• Human virus and bird virus reassort gene sequences
in pig, resulting in banded virus in pig and normal
human subject
• alteration of receptor specificity during replication of
an avian virus in pigs may occur both before and
after reassortment with a human virus
Monday, February 6, 2012

35. POSSIBLE MECHANISMS FOR THE
EMERGENCE OF PANDEMIC VIRUSES
• Bird virus adapts to virulent state in pigs, resulting in
diseased human subject
• an avian virus may become adapted in pigs to the extent
that it would not require reassortment with a human virus
for efficient replication in humans
Monday, February 6, 2012

36. POSSIBLE MECHANISMS FOR THE
EMERGENCE OF PANDEMIC VIRUSES
• Bird virus and human virus reassort gene sequences
in human, resulting in banded virus in normal human
subject
• direct transmission and reassortment in humans
• eg. outbreak in Hong Kong in 1997
Monday, February 6, 2012

37. POSSIBLE MECHANISMS FOR THE EMERGENCE
OF PANDEMIC VIRUSES
• Bird virus adapts to virulent state in diseased
humans, resulting in diseased human subject
• adaption in humans
• outbreak in Hong Kong in 1997
Monday, February 6, 2012

38. PREVENTION AND C0NTROL
! 1. Vaccines
! ! a. Inactivated
! ! ! 1.whole
! ! ! 2.subunit
! ! b. Live attenuated- nasal spray available 2003
! ! c. Recombinant - cDNA derived-in preparation
! 2. Antiviral Drugs
! ! a. Amantadine
! ! b. Neuraminidase inhibitors -oseleotamivir
! ! highly specific - based on crystal structure
! ! block active site
! ! c. Extremely important to use in conjunction!
! ! with a rapid diagnostic kit.
Monday, February 6, 2012