Influenza Virus Vaccine Composition 20052006

1
Influenza Virus Vaccine Composition 2005-2006

• Roland A. Levandowski, M.D.
• Division of Viral Products

Prepared for Vaccines and Related Biological
Products Advisory Committee 16-17 February 2005
2
VRBPAC Committee Recommendation

• Selection of influenza A (H1 and H3) and B
  viruses for 2005-2006 influenza vaccines for use
  in the United States

3
Why Change Strains in Influenza Vaccines?

• Vaccine efficacy relates to
• Vaccine immunogenicity (potency)
• Match of vaccine HA/NA with wild-type viruses
• First evidence of reduced vaccine effectiveness
  because of antigenic drift 2 years after first
  vaccines licensed for use in United States
• Antigenic drift of HA/NA continuous in influenza
  A and B viruses

4
Questions to Be Answered for Strain Changes Every
Year

• Are new (drifted or shifted) influenza viruses
  present?
• Are these new viruses spreading in people?
• Do current vaccines induce antibodies against the
  new viruses (HA)?
• Are strains suitable for vaccines available?

5
Review of Strain Selection 2004
6
Strain Selection 2004New Strains Present?

• Influenza A H1N1/H1N2? NO
• HA of all strains were similar to the vaccine
  strain

7
Strain Selection 2004New Strains Present? (Cont)

• Influenza A H3N2? YES
• First identification of antigenically
  distinguishable A/Fujian-like viruses in February
  2003
• By 2004, HA of most H3N2 strains were
  antigenically distinguishable from the vaccine
  strain

8
Strain Selection 2004New Strains Present?
(Cont)

• Influenza B? YES
• HA of majority of strains in 2004 were similar to
  B/Shanghai/361/2002 (antigenic lineage not in the
  vaccine 2003-2004)
• HA of minority of viruses were similar to the
  2003-2004 vaccine strain B/Hong Kong/330/2001

9
Strain Selection 2004 New Viruses Spreading?

• YES
• A/Fujian-like viruses had become widespread
  during 2003-2004
• B/Shanghai/361/2002-like strains predominant in
  Asia, Europe and North America

10
Strain Selection 2004 Viruses Inhibited by
Current Vaccines?

• Partial/variable NO
• A/Fujian-like strains some well-inhibited
  others poorly inhibited
• B/Shanghai like strains not inhibited by vaccine
  but B/Hong Kong-like strains still mostly well
  inhibited

11
Strain Selection 2004 Strains Suitable for
Manufacture Available?

• YES
• Manufacturing depends on egg-adapted strains
  (wild-type or reassortant)
• A/Fujian-like wild type and high growth
  reassortants available (A/Wyoming/3/2003 X 147)
• B/Shanghai-like wild type strains suitable for
  manufacturing (including B/Jilin/20/2003 and
  B/Jiangsu/10/2003)

12
Strains Selected for 2004-2005

• A/New Caledonia/20/99 (H1N1)-like
• B/Shanghai/361/2002-like
• B/Jilin/20/2003
• B/Jiangsu/10/2003
• A/Fujian/411/2002 (H3N2)-like
• A/Wyoming/03/2003

13
Implications of Strain Selection

• Preparation of vaccines was on schedule for
  2004-2005
• The supply of vaccine was expected to match the
  demand predicted by previous years experiences

14
Influenza Vaccine Shortage 2004

• January to August 2004
• Manufacturing progressed on schedule with two new
  strains
• Anticipated approximately 100 million doses for
  2004-2005
• August 2004
• Chiron notified regulatory authorities about
  sterility issue and investigation to identify
  cause and implement correction
• Chiron made a public announcement indicating
  possible delay in distribution and reduction in
  amount of vaccine available

15
Influenza Vaccine Shortage 2004

• October 2004
• MHRA (the UK regulatory authority) announced
  suspension of the Chiron license to manufacture
  inactivated influenza vaccine for 3 months
• November 2004
• Review of situation and consultation between FDA
  and MHRA made it clear that vaccine planned by
  Chiron would be unavailable

16
Response to Vaccine Shortage

• FDA
• Evaluation of manufacturers for use of unlicensed
  vaccines under IND
• Consultation with manufacturers to discuss
  regulatory mechanisms such as accelerated
  approval, fast track and priority review to
  facilitate licensing new vaccines

17
Response to Vaccine Shortage

• CDC
• Review and communication of use recommendations
• Coordination of distribution of existing vaccine
  supplies
• Coordination of acquisition and use of vaccines
  under IND

18
Response to Vaccine Shortage

• NIH
• Support for clinical studies of vaccines under
  IND
• Continuing support for development of new
  vaccines including cell culture based,
  recombinant DNA, and adjuvanted influenza
  vaccines

19
Response to Vaccine Shortage

• PHS/HHS
• Global consultation with manufacturers and other
  national regulatory authorities to identify
  alternate vaccine supplies

20
Current Vaccine Availability

• CDC recommendations (27 January 2005)
• http//www.cdc.gov/flu/protect/lateseasonguidance.
  htm
• Licensed influenza vaccines for 2004-2005
• Inactivated vaccine (Aventis)
• Live attenuated vaccine (MedImmune)
• IND influenza vaccines for 2004-2005
• GSK
• Berna Biotech

21
Timelines for Vaccine Production
22
Time to First Trivalent Vaccine Lot after Strain
Change
23
WHO Recommendations for Influenza Vaccine
CompositionSouthern hemisphere 2005

• It is recommended that vaccines to be used in
  the 2005 season (southern hemisphere winter)
  contain the following
• an A/New Caledonia/20/99(H1N1)-like virus
• an A/Wellington/1/2004(H3N2)-like virus
• a B/Shanghai/361/2002-like virus

24
WHO Recommendations for Influenza Vaccine
CompositionNorthern hemisphere 2005-2006

• It is recommended that vaccines to be used in
  the 2005-2006 northern hemisphere influenza
  season contain the following
• an A/New Caledonia/20/99 (H1N1)-like virus
• an A/California/7/2004 (H3N2)-like virus
• a B/Shanghai/361/2002-like virus

25
Question for Committee Recommendation

• What strains should be recommended for the
  antigenic composition of the 2005-2006 influenza
  virus vaccine?
• Based on
• Epidemiology and antigenic characteristics
• Serologic Responses
• Availability of candidate strains