Synthetic Vaccines

264 Pages·2012·2.748 MB·2-260\264

by  Cornelis J.M. Melief (Eds.)

ASSOCIATE EDITORS
K. FRANK AUSTEN
HarvardMedicalSchool,Boston,Massachusetts,USA
TASUKU HONJO
KyotoUniversity,Kyoto, Japan
FRITZ MELCHERS
UniversityofBasel,Basel,Switzerland
JONATHAN W. UHR
UniversityofTexas,Dallas,Texas,USA
EMIL R. UNANUE
WashingtonUniversity,St.Louis,Missouri,USA
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CONTRIBUTORS
Numbersinparenthesesindicatethepagesonwhichtheauthors’contributionsbegin.
MyriamAre´valo-Herrera
Malaria Vaccine and Drug Development Center/Immunology Institute,
UniversidaddelValle,Cali,Colombia(107)
RamonArens
Department of Immunohematology and Blood Transfusion, Leiden Uni-
versityMedicalCenter,Albinusdreef2,Leiden,TheNetherlands(217)
SilviaAriotti
DivisionofImmunology,TheNetherlandsCancerInstitute,Plesmanlaan,
Amsterdam,TheNetherlands(203)
JaapW.Back
PepscanTherapeutics,Lelystad,TheNetherlands(33)
WinfriedBarchet
Institute for Clinical Chemistry and Clinical Pharmacology, University
ClinicBonn,Bonn,Germany(1)
NoraCe´spedes
Biochemstry Department, University of Lausanne, Epalinges, Switzer-
land; Malaria Vaccine and Drug Development Center/Immunology
Institute,UniversidaddelValle,Cali,Colombia(107)
GiampietroCorradin
Biochemstry Department, University of Lausanne, Epalinges, Switzer-
land(107)
DmitriV.Filippov
Leiden Institute of Chemistry, Leiden University, Leiden, The Nether-
lands(177)
JohnB.Haanen
DivisionofImmunology,TheNetherlandsCancerInstitute,Plesmanlaan,
Amsterdam,TheNetherlands(203)
ix
x Contributors
GuntherHartmann
Institute for Clinical Chemistry and Clinical Pharmacology, University
ClinicBonn,Bonn,Germany(1)
So´cratesHerrera
Malaria Vaccine and Drug Development Center/Immunology Institute,
UniversidaddelValle,Cali,Colombia(107)
AndreyV.Kajava
CRBM,CNRS,UniversityofMontpellier,Montpellier,France(107)
SelinaKhan
Department of Immunohematology and Blood Transfusion, Leiden
UniversityMedicalCentre,Leiden,TheNetherlands(177)
JohannesP.M.Langedijk
Crucell, Innovation and Discovery Laboratory, Leiden, The Netherlands
(33)
CornelisJ.M.Melief
Department of Immunohematology, Leiden University Medical Center
and Immune System Activation (ISA) Pharmaceuticals, Leiden, The
Netherlands(77)
FerryOssendorp
Department of Immunohematology and Blood Transfusion, Leiden
UniversityMedicalCentre,Leiden,TheNetherlands(177)
EstherD.Quakkelaar
Department of Immunohematology, Leiden University Medical Center,
Leiden,TheNetherlands(77)
TonN.Schumacher
DivisionofImmunology,TheNetherlandsCancerInstitute,Plesmanlaan,
Amsterdam,TheNetherlands(203)
JasperG.vandenBoorn
Institute for Clinical Chemistry and Clinical Pharmacology, University
ClinicBonn,Bonn,Germany(1)
SjoerdH.vanderBurg
DepartmentofClinicalOncology,ExperimentalCancerImmunologyand
Therapy, Leiden University Medical Center, Albinusdreef 2, Leiden,
Netherlands(51)
Contributors xi
ThorbaldvanHall
DepartmentofClinicalOncology,ExperimentalCancerImmunologyand
Therapy, Leiden University Medical Center, Albinusdreef 2, Leiden,
Netherlands(51)
AntonioVerdini
Biochemstry Department, University of Lausanne, Epalinges, Switzer-
land(107)
HelenY.Wang
Department of Pathology and Immunology, Center for Cell and Gene
Therapy,BaylorCollegeofMedicine,Houston,Texas,USA(151)
Rong-FuWang
Department of Pathology and Immunology, Center for Cell and Gene
Therapy,BaylorCollegeofMedicine,Houston,Texas,USA(151)
GijsG.P.Zom
Department of Immunohematology and Blood Transfusion, Leiden
UniversityMedicalCentre,Leiden,TheNetherlands(177)
PREFACE
ThisvolumeofAdvancesinImmunologyisentirelydevotedtothescience
of synthetic vaccine development. While it is hard to exaggerate the
public health importance of preventive vaccination, no fully effective
preventive vaccines exist for many infectious diseases, with, as of this
writing, the prominent examples of AIDS, tuberculosis, and malaria.
Therapeutic vaccines are an even greater challenge, but as discussed in
thesechapters,someinitialsuccesseshavebeenbooked.Itismyconvic-
tionthatforfurtherdevelopmentofpowerfulvaccines,knowledgeofthe
optimal chemical structure of immunogens needs to be combined with
optimal insights into how the required innate and adaptive immunity
can best be stimulated. This compilation of reviews constitutes a strong
plea toward rational design of vaccines to address the unsolved vaccine
challenges, away from empiric approaches with complicated poorly
understood viral or bacterial vectors and away from live attenuated
organisms. This approach requires detailed insights into how best to
stimulateinnate,aswellasBandTcellresponsesandintoregulationof
theseresponsesanddelineatesanexcellentcareerpathforanewgenera-
tion of immunologists and vaccinologists. In Chapter 1, van den Boorn
etal.elaborateingreatdetailthenatureofpathogen-derivednucleicacids
thatstimulateinnateandadaptiveimmuneresponses,illustratinglucidly
how these well-defined sequences can be used as, e.g., adjuvants in
synthetic vaccines and combinatorial immunotherapeutic approaches.
In Chapter 2, Back and Langedijk discuss how detailed knowledge of
thedynamiccrystalstructureoftheHIVenvelopeprovidesnovelinsights
that can lead to the development of a more efficient vaccine capable of
inducingneutralizingantibodiesagainstHIV.InChapter3,vanHalland
vanderBurgdissectthehistoryofpeptidevaccinestoinducetherapeutic
T cell responses and discuss the importance of the presence of helper T
cell epitopes, the necessity of uptake by professional antigen-presenting
cells, biodistribution, influence of adjuvants, peptide length, peptide
affinity,andmodeofadministration.InChapter4,QuakkelaarandMelief
review the use of synthetic peptide vaccines in primates and in clinical
trials.Thecombinedevidenceshowsthatsyntheticlongpeptidevaccines
are more effective than exact MHC class I binding peptide vaccines
because the long peptides contain helper T cell epitopes and require
processing by dendritic cells (DC), the prime initiators of immune
responses. In Chapter 5, Corradin et al. discuss the history of peptide
xiii
xiv Preface
synthesis and provide a gripping overview of the current status of long
peptide vaccines against malaria. In Chapter 6, Wang and Wang deliver
arguments on how synthetic long peptide vaccines can be further
improved by equipping them with cell-penetrating sequences, allowing
prolonged DC antigen presentation. Another highly interesting effi-
ciency-improvingstepcanbeachievedbycovalentcouplingthesynthetic
peptides to a TLR ligand, as illustrated in Chapter 7 by Zom et al. In
Chapter8,Ariottietal.demonstratetheimportanceoftheinductionand
persistence of tissue resident memory T cells. Surely vaccines need to
induce such cells for long-term protection against potential invaders of
these tissues. Last but not least, in Chapter 9, Arens draws an analogy
between the immune evasion strategies operating in malignant tumors
and those employed by persistent viruses and points out strategies to
counteract these mechanisms. Together these chapters were a great joy
to compile and to read. Undoubtedly, they will be a rich source of in-
formation and ideas that can help to develop a new generation of mole-
cularlydefinedvaccinestoaddressunsolvedproblemsinpreventiveand
therapeuticvaccination.
1
CHAPTER
Nucleic Acid Adjuvants:
Toward an Educated Vaccine
Jasper G.van den Boorn,Winfried Barchet, and
Gunther Hartmann
Contents 1. AShortVaccinationHistory 2
2. TheImmuneSystemasSensoryTissue 5
2.1. Innateimmunecellactivation 5
2.2. Adaptiveimmunecellactivation 6
3. WhySomeVaccinesJustDoNotWork 8
3.1. Liveattenuatedvaccines 8
3.2. Inactivatedvaccines 9
3.3. Mycobacteriumtuberculosis:Differentially
expressedantigens 9
3.4. Denguevirus:Antibody-dependent
enhancementofinfection 10
3.5. HIV:Highantigenicdrift 11
4. SynergizingInnateImmuneStimuli 12
4.1. TLR9activationbyCpGODN 13
4.2. SmallmoleculeandsinglestrandedRNA(ssRNA)
agonistsofTLR7/8 14
4.3. PolyI:CandderivativesactivateTLR3inthe
endosomeandMDA-5inthecytosol 15
4.4. 50-TriphosphateRNAdetectionbyRIG-I 15
4.5. RecognitionofcytosolicDNAby
STING-dependentpathwaysandtheAIM2
inflammasome 16
5. TherapeuticVaccination:JustaShotAway? 16
5.1. Therapeuticcancerimmunization 17
5.2. Immunosurveillanceandimmunomodulation 17
InstituteforClinicalChemistryandClinicalPharmacology,UniversityClinicBonn,Bonn,Germany
AdvancesinImmunology,Volume114 #2012ElsevierInc.
ISSN0065-2776,DOI:10.1016/B978-0-12-396548-6.00001-9 Allrightsreserved.
1
2 JasperG.vandenBoornetal.
6. TowardtheIntegratedResponse:Cross-Primingof
CytotoxicTCellImmunity 18
6.1. Negativeregulationofcross-presentationbyNK
cellsviaDR5 19
6.2. Augmentationofcross-presentationbyNKTcells 19
6.3. Cross-presentationdependsontheDCsubset 20
6.4. AntigentargetingtospecificDCsubsets 20
7. Conclusion 21
Acknowledgments 22
References 22
Abstract Twostrikingfactssurroundthepracticeofvaccination:Itisthesole
medicalapproachtohavefullyannihilatedadisease,yetthedevel-
opmentofmosteffectivevaccinestookplacewithoutconsidering
the intricate cellular processes they wish to effectuate. While
extremelypotentvaccineshave beendevelopedthatcanprotect
practicallyalifetimeafterasingledose,numerousothervaccines
have utterly failed or provide only marginal protection. Here,we
aimtoillustratewhythisdifferenceinefficacyexists,andunderline
whyspecificcytotoxicTcell-inducingvaccinescouldcombatper-
sistentmajordiseases.Moreover,wediscusshowthecombinatorial
useofnucleicacidadjuvantsinvaccinescouldaidthedevelopment
ofthelatterandmovevaccinedesignfromtheempiricalstageinto
aneraof‘‘educateddesign.’’
1. A SHORT VACCINATION HISTORY
Thebasicunderstandingthattheburdenofinfectiousdiseasebringswith
it a form of protection from reinfection, already dates back to several
centuries B.C. when people noticed that they rarely acquired the same
disease twice, at least not to the same extent of morbidity (Plotkin and
Plotkin, 2008). It took some time before mankind actively exploited this
‘‘memory’’ phenomenon. The classical view states that it was not until
1796thatEdwardJennerpioneeredandcarriedouthisfamoussmallpox
vaccinations,usingthecowpoxvirusasinoculum(Jenner,1798).Thereby
he allegedly carried out the first human vaccinations. While these were
indeedthe first ‘‘vaccinations,’’a term coinedby Jenner himself to iden-
tifythebovineoriginofhisinoculum,hebasicallyoptimizedamethodof
immunizationthathadalreadybeenknownforcenturies.
The trail of active human immunization, in particular against small-
pox, leads back wellbeyond the dark ages. Itis highly likely that Jenner
was inspired by the practices of the Dutch cattle trader Geert Reinders,
whomanagedtostopthespreadofcowpoxinhisregionaround1774by
NucleicAcidAdjuvants:TowardanEducatedVaccine 3
deliberately reinfecting cows that recovered from cowpox with scabs
from recently infected animals. Reinders performed impressive funda-
mental work. In his age he documented that cows previously infected
with cowpox produced offspring that were temporarily protected from
this disease. Additionally, he described that deliberate reinfection of
these ‘‘maternally protected’’ animals, or otherwise previously cowpox-
diseasedanimals,actuallyprotectedhiscattlefromcowpoxforalifetime.
Thereby he was the first to document maternal inherited immunity as
wellasfunctionalboosterimmunizations.
Deliberateinfectiontoconferprotectionagainstsmallpoxactuallyhas
itsrootsinreligiousrites.Practicestotherebyprotectagainstthedisease
were already carried out in India in 1500 B.C. While these early days of
immunization remain obscure, the practice of supplying fresh smallpox
scab-materialtohealthyindividualstoinduceimmunity(aprocesscalled
variolation), started to become more common in sixth century China.
People ground dried smallpox-scabs from lightly diseased people and
applied these in wet cloths to the noses of healthy individuals to induce
protection.Whileotherpracticescoexisted,likesleepingnexttodiseased
peopleandwearingtheirusedclothing,thepracticeofvariolationslowly
spread westwards. Via popular healers in Africa and the Near East,
variolation evolved to involve the scratching of the skin with a sharp
object and inserting ‘‘serum’’ material extracted from fresh smallpox
scabs.
TheeffortsoftheGreekJamesPylarinofurtherpropagatedtheuseof
variolation, initially throughout the Ottoman Empire (Alivisatos, 1934).
After completing his medical studies in 1679 in Padua and wandering
through Europe as a court physician, he embarked on studying variola-
tioninConstantinopleby1701.ShortlyafterhisarrivalinConstantinople
Pylarino successfully variolated three children and thereby protected
them from a local smallpox epidemic. The success of his approach was
quickly recognized and spread accordingly as ‘‘the Greek method.’’
Pylarino’s accomplice Emanuel Timoni further propelled the method to
popularity. He communicated a paper on effective variolation to the
English Royal Society of Medicine in 1713. It was not until 1717 that
variolation was introduced broadly to Europe, after Lady Mary Wortly
Montagu undertook a trip to Turkey and Constantinople. Via her
subsequent efforts variolation was introduced to the royalty of Europe
andeventuallytothecommonpeople.
Being a relatively common (although still risky and potentially muti-
lating) practice at the end of the 1700s, Reinders basically extrapolated
variolationtohiscowsinanattempttoprotecthiscattle.Intheprocess,he
described the foundations of adaptive immunity. Jenner likely knew
about the immunization practices of Geert Reinders, since Reinders