ࡱ> }| H( / 0DArialngsRomanttTu 0DTimes New RomanttTu 0 DWingdingsRomanttTu 0 A .  @n?" dd@  @@`` 6 " !#$21   **4 5 0AA@8  !ʚ;ʚ;g4NdNdT 0ppp@ <4dddd@w 0t0u <4BdBd@x 0t|9___PPT10 6___PPT9m Fuʙ jSJFIF``"Photoshop 3.08BIM``8BIM x8BIM8BIM 8BIM 8BIM' 8BIMH/fflff/ff2Z5-8BIMp8BIM8BIM8BIM@@8BIM8BIMu Untitled-1 8BIM8BIM p ` TJFIFHHAdobed             "?   3!1AQa"q2B#$Rb34rC%Scs5&DTdE£t6UeuF'Vfv7GWgw5!1AQaq"2B#R3$brCScs4%&5DTdEU6teuFVfv'7GWgw ?sZִI'@Sc?!`[us:&)V_c?РF6路}UqobˋuuحZަ,kr1􍲺ՙq]aNF[an[.l*wՅWn%YZ7Y'>f+?Oi}Wgv~Dnәlу]0wi=xꘙm 'Vzj ف uݯ2]Ժó}'T\oLj-mmM[-.>ʒi6Fg8BIM!UAdobe PhotoshopAdobe Photoshop 6.08BIM XICC_PROFILE HLinomntrRGB XYZ  1acspMSFTIEC sRGB-HP cprtP3desclwtptbkptrXYZgXYZ,bXYZ@dmndTpdmddvuedLview$lumimeas $tech0 rTRC< gTRC< bTRC< textCopyright (c) 1998 Hewlett-Packard CompanydescsRGB IEC61966-2.1sRGB IEC61966-2.1XYZ QXYZ XYZ o8XYZ bXYZ $descIEC http://www.iec.chIEC http://www.iec.chdesc.IEC 61966-2.1 Default RGB colour space - sRGB.IEC 61966-2.1 Default RGB colour space - sRGBdesc,Reference Viewing Condition in IEC61966-2.1,Reference Viewing Condition in IEC61966-2.1view_. \XYZ L VPWmeassig CRT curv #(-27;@EJOTY^chmrw| %+28>ELRY`gnu| &/8AKT]gqz !-8COZfr~ -;HUcq~ +:IXgw'7HYj{+=Oat 2FZn  % : O d y  ' = T j " 9 Q i  * C \ u & @ Z t .Id %A^z &Ca~1Om&Ed#Cc'Ij4Vx&IlAe@e Ek*Qw;c*R{Gp@j>i  A l !!H!u!!!"'"U"""# #8#f###$$M$|$$% %8%h%%%&'&W&&&''I'z''( (?(q(())8)k))**5*h**++6+i++,,9,n,,- -A-v--..L.../$/Z///050l0011J1112*2c223 3F3334+4e4455M555676r667$7`7788P8899B999:6:t::;-;k;;<' >`>>?!?a??@#@d@@A)AjAAB0BrBBC:C}CDDGDDEEUEEF"FgFFG5G{GHHKHHIIcIIJ7J}JK KSKKL*LrLMMJMMN%NnNOOIOOP'PqPQQPQQR1R|RSS_SSTBTTU(UuUVV\VVWDWWX/X}XYYiYZZVZZ[E[[\5\\]']x]^^l^__a_``W``aOaabIbbcCccd@dde=eef=ffg=ggh?hhiCiijHjjkOkklWlmm`mnnknooxop+ppq:qqrKrss]sttptu(uuv>vvwVwxxnxy*yyzFz{{c{|!||}A}~~b~#G k͂0WGrׇ;iΉ3dʋ0cʍ1fΏ6n֑?zM _ɖ4 uL$h՛BdҞ@iءG&vVǥ8nRĩ7u\ЭD-u`ֲK³8%yhYѹJº;.! zpg_XQKFAǿ=ȼ:ɹ8ʷ6˶5̵5͵6ζ7ϸ9к<Ѿ?DINU\dlvۀ܊ݖޢ)߯6DScs 2F[p(@Xr4Pm8Ww)KmAdobed@   1A"B#3%5 !1"Qa2bAqBRr ?|uB@ 4H %6s$M0Aq2rQWUYQ& ']"<ƥbTvԟjs mQKC|]]7Uix c 3aHkf.Q]uL? sfo1UN&IoOmW?#ȭIHfjzTbjhë`V}?mԬ,,!.zΉPdY.y5ۙ2"-*︭h@Z7vC co 4hv2K'pxǕ@|TDUUDDEUU_"'ڪr'XL:M~?^VK%su)XUUokE˵T !I@:Q7a!jA[|u[鶌j0c=' (+Z,"޻yUjnҗxg0ذX&ݩn)aj6bLkX*#\!'Lx0Aor?q: s741n|f:5^kohϙ1Tqƕ^CZK@Eo{ȚQ`G;X4t|.IM.FHW9Xh OwqvB5cf1,>HYN @A=rjMNaYM%8}JO֌0FG&L##.&љcS6R\rT;Ds/tLJpr$9kHD";|TiûD.2YSs S{Hct\aQVy b dӢw Yf Zia N4ڻu)l2Xy{*5N*ӑm4<`~9'WA n<ٍhM5]*i_hRqpU޵_*b&W[. 5 DDX/R6HUutC7ur+$x><C yIHVwje '椺]bcTyJcFEKrی #jzh δQZst:rSԎfV#0K#<J5GT(XPI ʧCu9XY|kLf䴳b@ 3A   The state of the land CHAVI is funded by the NIH and focuses on : Acute infection : host  virus interactions including polymorphisms of the host and genetic variability of the virus : this will allow to select viruses as immunogens Antibodyome project : Profile the full antibody repertoire to the HIV envelope glycoprotein Define the B cell subsets that can generate Abs to HIV envelope Develop single cell assays that can measure B cell responses to HIV envelope Mucosal immunity and assays -ZZZZZZZZ-      ,   The state of the landFIAVI is an international vaccine consortium working to : Develop novel vectors that can induce protective immunity Identify correlates of immune protection in the Attenuated SIV model Develop standardized methodologies to quantify immune responses Develop immunogens that can induce broadly neutralising antibodies to HIV *99,    The state of the landGSeveral other networks have been formed in Europe ( EUROVAC and other European consortia ) , Africa ( AAVP , SAAVI) , Asia ( the Chinese CDC ) to accelerate HIV vaccine development These consortia focus on Novel vectors Novel immunogens Neutralizing antibodies and other strategies to neutralize HIV including HIV tat 6tu V    'Challenges in developing an HIV vaccine(($ CORRELATES OF PROTECTION(Little is known about the correlates of protection to HIV Current studies involve the studies of : Acute infection Elite controlers or LTNPs Exposed uninfected individuals Studies have focused on the use of assays that can measure limited profiles of immune responses including cells and functions Polyfunctional T cells have been associated to vaccine induced protection in malaria vaccines How can we induce long term memory T of B cells BfZLZZfL>} CORRELATES OF PROTECTION(rLimited number of studies on the role of innate immunity and mucosal immunity Innate immunity has its own modalities to control viral load but also will shape the adaptive immune responses Mucosal immune responses are critical since they are the first to allow control of virus at sites of entry Lack of reliable assays to measure innate of mucosal immune responses ssNEUTRALISING ANTIBODIES Immunogens that can induce neutralizing antibodies are lacking : Different conformations of HIV envelope ( need for strong structural biologists ) Role of HIV envelope glycosylation in preventing the development of neutralizing antibodies How to prevent viral escape from neutralizing antibodies Cross-reactivity with self proteins and molecules prevents the development of high affinity neutralizing antibodies What are the proper vectors and immuogens to use BAZ_Z3ZA_36 | -   ADJUVANTS  \Adjuvants that can help boost innate and specific immunity in humans are lacking Knowledge of basic mechanisms of adjuventation of immune responses is lacking : Cellular targets: DCs and DC subsets , NK cells , Monocytes Molecular targets : TLRs , RNA and DNA sensors Current platforms to measure adjuventation of immune responses are lacking <mNmNl j 4 5 $ANIMAL MODELS The primate model has raised a lot of issues over the past few years and specially in light of the results of the STEP trial results Most importantly : How and where should we measure protective immunity Which viral strains should we use for challenge : Homologous or heterologous :hh INNATE IMMUNE RESPONSES (eWhich cells to measure Which molecules to quantify Where to look at Need for assays and targets (II$ MUCOSAL IMMUNE RESPONSES (How to sample Gender differences Cellular and molecular targets Need knowledge on effector mechanisms and cells Need for robust reliable assays ,CZSZCS,U9"What can CANADA CONTRIBUTE PERSONAL THIOUGHTS CANADA s contribution to the Global HIV Vaccine Enterprise Vaccine InitiativeQQ I 9 Contribute to the innate and mucosal immunity agenda : Sex resistant workers and acute infection cohorts Mechanisms of innate and mucosal immunity by identifying cells and molecules involved Gender differences Assays to measure innate and mucosal immune responses Interplay between adaptive and innate immunity This will help the development of adjuvants Development of core facilities for the performance of standardised assays to measure immune responses Development of a systems biology approach to vaccine development with strong focus on research in human t 7 2  72  &_    /@  0` j\Vtff3Ÿ` fBff33` .6aR3fi` 3fff` 3fff̙` fff33` f` 3'\m3fff` 33Ţ>?" dd@,?oFd(@ nK<)oAd=nKko2 n?" dd@   @@``PT   = ` `6p>>  y @  (    <Tʍ "P `   ['Cliquez pour modifier le style du titre( (H  0P͍ " `  vCliquez pour modifier les styles du texte du masque Deuxime niveau Troisime niveau Quatrime niveau Cinquime niveau4 w  0Ӎ "` @  X*   0؍ "`   Z*   0ݍ "``  Z* T `P  "`PhB B s *D1" PP   <1"`,$D 0 H0    <\1"`~,$D 0 H0    <@1"~H,$D 0 H0    <1"G,$D 0 H0 B  s *޽h ? fBff33___PPT10i. a+D=' = @B + Quadrant   0   P (    <1"p  H0   <, "`p  ['Cliquez pour modifier le style du titre( (  0 "D T  l8Cliquez pour modifier le style des sous-titres du masque9 9  0 "` `  X*   0\! "`   Z*   0% "` `  \* T   "  B@*1"t H0   </1"| H0   BH31"|p H0   <51"zp H0 hB  B s *D1"  B91" H0 B  s *޽h ? fBff33___PPT10i. a+D=' = @B + 0  H.(  H H 0 P    P*   H 0̯     R*  d H c $ ?  : H 0  0  vCliquez pour modifier les styles du texte du masque Deuxime niveau Troisime niveau Quatrime niveau Cinquime niveau4 w H 6 _P   P*   H 6t _   R*  H H 0޽h ? 3380___PPT10.Vk# 0  0(  x  c $|H`p  x  c $$ID T  H  0޽h ? 33___PPT10i.Pkp{da+D=' = @B +'   0L0 &0 (   ~  s * `     B ?4  At least 29 million new infections could be prevented with greater access to proven HIV prevention tools and information. However, fewer than one in five people at risk worldwide has access to prevention interventions, such as condoms, circumcision behavior-change programs, or STD treatment. An HIV vaccine is the best long-term hope for controlling the epidemic, especially in developing countries. Efforts to develop an HIV vaccine should greatly increase.0qsZ;0qsZx""n  :7H  0޽h ? B@3X^y___PPT10i.pq0+D=' = @B +?   0L0 >6@(  ~  s *w0 `     B ?`nf^___PPT9@8 (<First phase I HIV vaccine trial was conducted in 1987. Since then: More than 100 phase I/II trials & of more than 30 candidate vaccines & two phase III trials concluded, and one ongoing. We have learned: How to produce candidate vaccines that stimulate anti-HIV immune responses (although their immunogenicty need to be improved) That candidate vaccines protect animal models (partially) That candidates are safe and immunogenic in humans ( from phase I/II trials) Protective efficacy needs to be determined in (multiple) phase III trials. CplsZ2yplsZ2plsZ2RplsZ2C"y""Q"  7H  0޽h ? B@3X^y___PPT10i.pq0+D=' = @B +   0 |0(  |x | c $}P `    x | c $ܲ `  H | 0޽h ? 33___PPT10i.k XB+D=' = @B +   0 0(  x  c $dP `    x  c $  `  H  0޽h ? 33___PPT10i.kh+D=' = @B + 0 0(  x  c $T:`p  x  c $,;D T  H  0޽h ? 33___PPT10i.k+D=' = @B +   0 `X0(  Xx X c $3P `    x X c $4 `  H X 0޽h ? 33___PPT10i.[kOqS+D=' = @B +   0 @P0(  Px P c $pNP `    x P c $HO `  H P 0޽h ? 33___PPT10i.Vk+D+D=' = @B +   0 p0(  px p c $KP `    x p c $K `  H p 0޽h ? 33___PPT10i.nk$+D=' = @B +   0 PT0(  Tx T c $hP `    x T c $i `  H T 0޽h ? 33___PPT10i.Vk`T+D=' = @B +3   0 JB!!D(  D D Hw &q %Vaccine Clinical Development Process J%00%G(G( D <~2x iCandidate vaccine 0B  D 0k + F Registration 0 BR D s *jB D BDԔv v  D <(]n PPre-clinical studies 0B D 0L  tPhase I Safety Immuno 0B  D 08 h PPhase II Dose Safety 0B  D 0<` UPhase III Efficacy Safety 0B  D < < _Project file Project-based budget Project management (Gantt chart and Go/No Go decision points),`05B+@j   "     R  D s *XHR  D s *0 R D s * R D s *(R D s *H8 D 0ts ({  cRegistration Phase 400FjB D BDԔC P K jB D BDԔK S jB D BDԔC P 0C  D <tb 3  NResearch Phase$0F D <Уb  j  (Early Development Phase Proof-of-concept$)0)Ff  D <b g )  VLate Development Phase$0FjB D BDԔC `C  D <DCXc D0  D <'  D0  D <  F0  D <(./ n e Clinical lots 0B  X2 D 0 2 D <  J 0 s D <* /Medical Need Feasibilty, Scalability Market, IP*00-            D <,] L [IND 0 RB !D s *D3ԔppH D 0޽h ? 33___PPT10i.X c+D=' = @B +   0L0 P$(  ~  s *k(`p   f  B8 ?RX  < What are the correlates of immune protection against HIV infection and AIDS? Which immunogens and which vectors will allow the reproducible production of induce neutralizing antibodies? Do we have good adjuvants to induce broad and persistent immune responses What is the contribution of the innate and mucosal immune systems Do we have good animal models that can predict vaccine-induced primate protection experiments in terms of potential protection of humans? What is the impact of the genetic variability of HIV in terms of potential vaccine-induced protection?L0lsZ<0qsZ < ,V m g7H  0޽h ? B@3X^y___PPT10i.pq0+D=' = @B +   0 p\0(  \x \ c $P `    x \ c $ `  H \ 0޽h ? 33___PPT10i.mk +D=' = @B +   0 00(  x  c $$P `    x  c $ `  H  0޽h ? 33___PPT10i.k0+D=' = @B +   0 `0(  `x ` c $xP `    x ` c $ `  H ` 0޽h ? 33___PPT10i.mk'+D=' = @B +   0 h0(  hx h c $P `    x h c $H `  H h 0޽h ? 33___PPT10i.mk.+D=' = @B +   0 d0(  dx d c $ P `    x d c $  `  H d 0޽h ? 33___PPT10i.mkDA+D=' = @B +   0 t0(  tx t c $l#P `    x t c $& `  H t 0޽h ? 33___PPT10i.nk'+D=' = @B +  0 $f(  $\ $ 0L,@XW  The principal mode of AIDS transmission is through exposure of mucosal surfaces to HIV and HIV-infected cells Mucosal immunity is the first line of defense and represents 70% of the immune system The gut serves as a reservoir following HIV infection Mucosal immunization induces both local and systemic immunity Evidence that mucosal immunity (IgA, CTL) is associated with protection in HEPS subjects$Pb6 $ B-P` X RATIONALE FOR A MUCOSAL VACCINE !0! H $ 0޽h ? y___PPT10Y+D=' = @B +   0 x0(  xx x c $p.P `    x x c $) `  H x 0޽h ? 33___PPT10i.nkp/+D=' = @B + 0 @0(  x  c $lM`p  x  c $TD T  H  0޽h ? 33___PPT10i.kp+D=' = @B +   0 `R(  ~  s *N     s *M `  "H  0޽h ? fff3fZ̙___PPT10i.P+D=' = @B +(  0 0L8(  Ld L c $H    L s *TH 0   " H L 0޽h ? 3380___PPT10.YY`6r|i l >--'-- $jj--'@Times New Roman-. B$2 *Development of HIV   ."System@;-@Times New Roman-. B2 8Vaccines.-@Arial-. "2 ISTATE OF THE LAND .-@Arial-. 42 RWHAT CAN CANADA CONTRIBUTE IN .-@Arial-. 2 ZBASIC SCIENCES .-՜.+,08    On-screen ShowUniversit de Montral i ArialTimes New Roman Wingdings QuadrantDevelopment of HIV Vaccines HIV/AIDS:The problem A short history of HIV vaccinesTHE STEP TRIAL THE STEP TRIALThe field is rich The state of the land The state of the land The state of the landThe state of the land Slide 11(Challenges in developing an HIV vaccineCORRELATES OF PROTECTIONCORRELATES OF PROTECTIONNEUTRALISING ANTIBODIES ADJUVANTS ANIMAL MODELS INNATE IMMUNE RESPONSES Slide 19MUCOSAL IMMUNE RESPONSES What can CANADA CONTRIBUTE QCANADAs contribution to the Global HIV Vaccine Enterprise Vaccine Initiative  Fonts UsedDesign Template Slide Titles_0JVRZICJVRZIC  !"#$%&'()*+,-./0123456789:;<=>?@ABCDEFGHIJKLMNOPQRSTUVWXYZ[\]^_`abcefghijkmnopqrsuvwxyz{~Root EntrydO)Current UsertSummaryInformation(dPowerPoint Document( DocumentSummaryInformation8l