Watch the video of the presentation on Youtube:https://www.youtube.com/watch?v=E6CmOWR8klI&feature=youtu.be
Seasonal influenza continues to cause yearly epidemics resulting in severe disease and a significant number of deaths despite available vaccines and antivirals. Even more concerning is the ability of influenza virus to cause pandemics every 10-50 years. In the last years, we and other have characterized several features associated with virus virulence and tropism. In addition, new developments suggest the possibility of universal influenza virus vaccines that induce protective antibodies against conserved regions.
Prof. Adolfo García Sastre: Influenza epidemics and pandemics
1. Adolfo García-Sastre
Icahn School of Medicine at Mount Sinai, New York
CRIP, Center for Research on Influenza Pathogenesis
INFLUENZA
EPIDEMICS
PANDEMICS
8. Alicia Solórzano
Adolfo García-Sastre
Patty Aguilar
Chris Basler
Peter Palese
Mount Sinai
Terry Tumpey
Hui Zeng
Nancy Cox
Jacky Katz
CDC
David Swayne
USDA
Jeff Taubenberger
AFIP
17. 1918 VIRUS
What do we know now?
1. The 1918 virus is the only known human influenza virus
lethal to mice, ferrets, macaques and embryonated eggs
2. The glycoprotein (HA and NA) and non-structural (NS1
and PB1-F2 genes) of the virus contribute to enhanced
virulence
3. Viruses containing 1918 genes are sensitive to existing
antivirals
4. H1N1 based vaccines are protective
Would a 1918-like HIN1 virus be today as lethal as in
1918?
19. Rafa Medina
Balaji Manicassamy
Estanis Nistal-Villán
Adolfo García-Sastre
Tshide Tsibane
Chris Basler
Silke Stertz
Peter Palese
Mount Sinai
Petra Zimmermann
Osvaldo Zagordi
Silke Stertz
University of Zurich
Hanni Uusi-Kerttula
Rafa Medina
Universidad Católica de Chile
Xiangjie Sun
Terry Tumpey
CDC
Sharon Frey
Bob Belshe
SLU
20. ‘40 ‘50 ‘60 ‘70 ‘80 ‘00‘901918
H1N1
H2N2
H1N1
H3N2
A
B
EPIDEMIOLOGY OF HUMAN INFLUENZA
VIRUSES
‘10
1957
1968
1977
pH1N1
2009
23. 1918 “Spanish” flu
Pigs Humans
Classical swine flu Modern human H1N1
Sa
Ca2
Ca1
Cb
Receptor
binding site
Sb
Fusion peptide
Antigenic
sites
24. Pandemic H1N1 infections in humans
• Infections are primarily seen in children and young adults
• Serology studies show the presence of neutralizing
antibodies against 2009 H1N1 virus in people older than
65 yrs
Due to prior exposure to an H1 virus similar to 2009 H1N1?
25. Do antibodies to any specific H1N1 virus protect against SOIV
2009 H1N1?
Virus Type Year (lineage)
A/California/04/09 (6:2) H1N1 2009
1918-like or classical H1N1
1918 VLP H1N1 1918
A/swine/Iowa/30 H1N1 1930 (Classical)
A/Weiss/43 H1N1 1943 (1918-like)
A/New Jersey/8/76 H1N1 1976 (Classical?)
Human H1N1(1977-2007)
A/USSR/92/77 H1N1 1977
A/Houston/20593/84 H1N1 1984
A/Texas/36/91 H1N1 1991
A/Brisbane/59/07 H1N1 2007
Control (H3N2)
A/NT/60/68 H3N2 1968
A/Brisbane/10/07 H3N2 2007
26. Vaccination and challenge experiment
Vaccination
15mg
-28
Boost
15mg
Challenge (50 LD50)
-14
Body weight
& Survival
0Day
- 5 week old female C57B/6 mice
- Mice were vaccinated with 11 different inactivated viruses
- Challenged with Neth/09 strain
14
27. Inactivated vaccines based in classical swine viruses (1930-2009)
and in human H1N1 viruses (1918-1943) protect against lethal
infection with the new H1N1
30. Conclusions
-People carrying antibodies against H1N1 viruses
that circulated 1918-1950 and A/NJ/76 (vaccination)
are likely to be protected
- Pigs act as reservoirs for strains that become
antigenically “frozen” H3 and H1 viruses have also
established lineages in pigs in 1997-1998 and 2003-
2005. Swine H3N2v jumps frequently to humans.
33. Passive administration of sera from new H1N1 vaccinated humans
In collaboration with Bob Belshe
Vaccination (or exposure) to new H1N1 virus generates protective
immunity against 1918 virus
49. UNIVERSAL FLU VACCINES?
Repeated vaccination with influenza
virus chimeric HA vaccines induce
protective antibodies against
multiple subtypes of influenza virus.
Irina Margine Randy Albrecht
Florian Krammer
Rong Hai Patrick Wilson
Gene Tan S.A. Andrews
Peter Palese Jon Runstadler
50. cH4/3 DNA cH5/3 protein
boost
H3 protein
boost
Shanghai
(H7N9)
challenge
Control groups:
cH4/3 DNA + BSA + BSA
naïve (neg. contr.)
matched vaccine (pos. contr.)
4 weeks3 weeks3 weeks
Induction of protective levels of stalk-reactive
antibodies using chimeric HA constructs in
mice
51. cH4/3 DNA cH5/3 protein
boost
H3 protein
boost
Shanghai
(H7N9)
challenge
Control groups:
cH4/3 DNA + BSA + BSA
naïve (neg. contr.)
matched vaccine (pos. contr.)
4 weeks3 weeks3 weeks
Induction of protective levels of stalk-reactive
antibodies using chimeric HA constructs in mice
52. cH4/3 DNA cH5/3 protein
boost
H3 protein
boost
Shanghai
(H7N9)
challenge
Control groups:
cH4/3 DNA + BSA + BSA
naïve (neg. contr.)
matched vaccine (pos. contr.)
4 weeks3 weeks3 weeks
Induction of protective levels of stalk-reactive
antibodies using chimeric HA constructs in mice
Y
53. cH4/3 DNA cH5/3 protein
boost
H3 protein
boost
Shanghai
(H7N9)
challenge
Control groups:
cH4/3 DNA + BSA + BSA
naïve (neg. contr.)
matched vaccine (pos. contr.)
4 weeks3 weeks3 weeks
Induction of protective levels of stalk-reactive
antibodies using chimeric HA constructs in mice
Y
55. cHA vaccine protects against
challenge with H10 and H3 viruses
cH4/3 DNA + cH5/3 protein + H3 protein cH4/3 DNA + cH5/3 protein + cH7/3 protein
Titers in mouse lungs, day 3 postinfection
58. cH9/1 DNA cH6/1 protein cH5/1 protein
Control groups:
cH9/1 DNA + BSA + BSA
matched vaccine (pos. contr.)
Y
Induction of protective levels of stalk-reactive
antibodies using chimeric HA constructs in
mice
PR8 H1N1
FM1 H1N1
pH1N1
H5N1
H6N1
challenge
59. Vaccination with cHA constructs
protects from pH1N1
(A/Netherlands/602/09) challenge
positive control (matched inactivated)
cH9/1 DNA + cH6/1 protein + cH5/1 protein
cH9/1 DNA + BSA +BSA
Similar results for A/PR/8/34 H1N1 and A/FM/1/47
challenges
60. positive control (matched inactivated)
cH9/1 DNA + H1 protein/cH6/1 protein + cH5/1 protein/H1
protein
cH9/1 DNA + BSA +BSA
cHA constructs protect mice from
heterosubtypic challenge
H5N1 challenge H6N1 challenge
cH5/1 (H5 challenge) or cH6/1 (H6 challenge) protein was replaced by full
length H1 protein to exclude head-based protection
61. ELISA reactivity to Cal09
(pH1N1) protein
Protection is antibody mediated
cH9/1 + cH6/1 + cH5/1
cH9/1 + BSA +BSA
naïve serum
Naïve
Positive control
vector +BSA+BSA
cH9/1 + cH6/1 + cH5/1
Passive transfer of serum
protects from viral challenge
Days post challenge