Viral Vectors in Veterinary Vaccine Development: A Textbook PDF
Preview Viral Vectors in Veterinary Vaccine Development: A Textbook
Thiru Vanniasinkam Suresh K. Tikoo Siba K. Samal Editors Viral Vectors in Veterinary Vaccine Development A Textbook Viral Vectors in Veterinary Vaccine Development Thiru Vanniasinkam (cid:129) Suresh K. Tikoo (cid:129) Siba K. Samal Editors Viral Vectors in Veterinary Vaccine Development A Textbook Editors ThiruVanniasinkam SureshK.Tikoo SchoolofBiomedicalSciences VIDO-InterVac&SchoolofPublic CharlesSturtUniversity Health WaggaWagga,NSW,Australia UniversityofSaskatchewan Saskatoon,SK,Canada SibaK.Samal DepartmentofVeterinaryMedicine UniversityofMaryland,CollegePark CollegePark,MD,USA ISBN978-3-030-51926-1 ISBN978-3-030-51927-8 (eBook) https://doi.org/10.1007/978-3-030-51927-8 #SpringerNatureSwitzerlandAG2021 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeor part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations,recitation,broadcasting,reproductiononmicrofilmsorinanyotherphysicalway, andtransmissionorinformationstorageandretrieval,electronicadaptation,computersoftware,or bysimilarordissimilarmethodologynowknownorhereafterdeveloped. Theuseofgeneraldescriptivenames,registerednames,trademarks,servicemarks,etc.inthis publication does not imply, even in the absence of a specific statement, that such names are exemptfromtherelevantprotectivelawsandregulationsandthereforefreeforgeneraluse. Thepublisher,theauthors,andtheeditorsaresafetoassumethattheadviceandinformationin thisbookarebelievedtobetrueandaccurateatthedateofpublication.Neitherthepublishernor the authors or the editors give a warranty, expressed or implied, with respect to the material containedhereinorforanyerrorsoromissionsthatmayhavebeenmade.Thepublisherremains neutralwithregardtojurisdictionalclaimsinpublishedmapsandinstitutionalaffiliations. ThisSpringerimprintispublishedbytheregisteredcompanySpringerNatureSwitzerlandAG. Theregisteredcompanyaddressis:Gewerbestrasse11,6330Cham,Switzerland Foreword A viral vector vaccine consists of a nonpathogenic virus (the vector) that expresses protective antigen(s) of one or more heterologous pathogens. The pathogengenesequence(typicallyencodingsurfaceprotein)isengineeredby recombinant DNA methods to be inserted into the vector genome and expressedaspartofthevector’stranscriptionalprogram.Followingadminis- tration, a viral vector vaccine infects cells in the vaccine recipient. Some vectors are capable of limited vector replication in the recipient. Others are designed to be replication-defective and are restricted to a single cycle of infection.Asdescribedinthisconciseandveryusefulbook,theviralvector vaccineapproachisinnovativeandmultifaceted,hasresultedinanumberof successfulcommercialveterinaryvaccinestodate,andhastremendousprom- iseforfurtherdevelopment. Thefirstdemonstrationoftheefficacyofaviralvectorvaccinewasin1983 when a recombinant vaccinia virus expresses the hemagglutinin protein of a human influenza A virus was shown to be immunogenic and protective in hamsters [5]. This quickly led to the use of vaccinia virus to express the surface glycoprotein of rabies virus [4], resulting in a licensed veterinary rabiesvaccinethathashadsubstantialsuccessinrabiescontrol[3].Presently, a number of viruses are being developed as vaccine vectors. This book has excellentchaptersdescribingveterinaryvectorsandvaccines–bothcommer- cial and experimental – based on adenovirus, poxvirus, herpesvirus, para- myxovirus, classical swine fever virus, rhabdovirus, coronavirus, and alphavirus. Additional important chapters discuss practical considerations in developing live vector vaccines, including manufacturing and regulatory issues. Viral vector vaccines can be complicated and challenging to develop. Considerations include the numerous different available viral vectors and their diverse properties and strategies of construction and use; the biology and interplay of the vector, protective antigen, target host, and target patho- gen;andtherequirementsforprotectiveimmunity.However,withthiscom- plexity comes the possibility to develop vaccines that are particularly well suitedtotheiruse.Forexample,thephysicalstabilityofvacciniavirusplusits ability to infect by the oral route led to the rabies vaccine mentioned above thatcanbedeliveredinbaitleftoutdoors[3].Asasecondexample,herpesvi- rus of turkey provides a vector that is naturally nonpathogenic in poultry, is itself a vaccine against Marek’s disease virus, and can be engineered to v vi Foreword expressoneormoreadditionalantigensofpoultrypathogenstoyieldasingle virus that is a bivalent or multivalent vaccine (chapter “Paramyxoviruses as VaccineVectors”). Both RNA and DNA viruses are being developed as vectors, with DNA vectors presently represented by a greater number of commercial vaccines. RNAvirusestypicallyhavesmallgenomes,smallsetsofvectorproteinsand antigens,andlesscomplexbiologycomparedtoDNAviruses.Theyaremore limited in capacity for added foreign sequence and in some cases can have problemsofpointmutationsandinstabilityoftheforeignsequencethatneed to be monitored. DNA viruses typically have substantially larger genomes with more complex organizationandgeneexpression andalargerconstella- tion of vector proteins and antigens. They typically have greater genetic stability and have a greater capacity such that several foreign antigens can be expressed by a single vector virus. In both RNA and DNA virus vectors, theforeignsequenceusuallyisinsertedasasupernumerarygenethatdoesnot functioninthevectorreplicationcycle.Alternatively,inachimeric strategy, theencodedforeignproteinisafunctionalsubstitutionforanecessaryvector protein, such as replacing the surface glycoprotein of a rhabdovirus vector withthatofthetargetpathogen(chapter“RhabdovirusesasVaccineVectors for Veterinary Pathogens”), or the creation of a West Nile virus vaccine for horsesbythefunctionalsubstitutionofcodingsequencesforsurfaceproteins of the attenuated yellow fever virus vector with their counterparts from the pathogen[2]. Because virus vector vaccines are infectious and often are replication- competent in vivo, they must be designed to be nonpathogenic but also must have sufficient infectivity and antigen expression to be immunogenic andprotective.Thisbalancecanbedifficulttoachieveandisamajorissuein vector development. Nonpathogenicity may be achieved in various ways. Some vector viruses are chosen because they have low virulence in their native hosts. Some vectors are attenuated or are replication-defective in a non-native host due to vector-host incompatibility. Some vectors have been attenuatedbypassageincellcultureundervariousconditions(e.g.,extensive passage, suboptimal temperatures, cells from a non-native host, etc.), which canresultindeletionofviralgenesorgenomeregionsthatmaynotbeneeded invitrobutwhosedeletionisattenuatinginvivo.Thesedeletionsmayaffect vectormetabolism,tropism,virulence,andabilitytosuppresshostresponses. Attenuating point mutations also may appear in vector proteins or cis-acting nucleotide signals during passage or mutagenesis in vitro. Attenuation also maybeachievedbydirectmanipulationofthevectorgenomebyrecombinant DNA methods, such as to delete or rearrange genes or introduce point mutations. Deletion of vector genes that are essential for replication results in replication-defective vectors that can be propagated in cell culture by complementationwithvectorproteinssuppliedbyhelpervirusorengineered cells but which do not produce infectious virus in vivo (e.g., replication- defective adenovirus and alphavirus vectors, chapters “Adenovirus Vectors” and“Alphavirus-BasedVaccines”,respectively). Foreword vii Viral vector vaccines offer a number of important advantages, some of whichremaintobefullyinvestigatedanddeveloped.Thevectorsinfectcells inthetarget hostandexpressantigens intracellularly,inducinginnate,cellu- lar, antibody, mucosal, and systemic immunity. Broad immune stimulation enhances efficacy and provides immune regulatory crosstalk. Immunization typically is without need of an adjuvant (but see chapter “The Role of Adjuvants in the Application of Viral Vector Vaccines”) and often at rela- tively low dose (in the case of replication-competent vectors) and often without need for multiple administrations. Expression of antigen in vivo presents antigenic sites in native form. In these important aspects, viral vaccine vectors mimic natural infections. Some viral vector vaccines can be designedtobebivalentormultivalentbyexpressingmultipleantigens,andin some cases, the vector itself is a needed vaccine (e.g., herpesvirus of turkey noted above). Some vectors can be administered by multiple routes (e.g., topicalversusoralversusparenteral)suchthatanoptimalroutecanbechosen againstmucosalversussystemicpathogens.Somevectorsmayhaveadvanta- geous cell tropisms (e.g., efficient infection of antigen-presenting cells, with the potential for increased immunogenicity). Some vectors can be administered by convenient methods such as by spray, drinking water, or bait. The use of a virus vector that is not native to the target host avoids neutralization by maternal antibodies or immunity from prior infection with nativeviruses.Somereplication-competentvectorscanbeproducedrelatively efficientlyandcheaply.Usingavectortoexpressisolatedgenesofavirulent pathogenavoidstheneedtohandletheintactinfectiouspathogen. Global human health is threatened by a number of emerging pathogens (primarily viruses) originating from animals, including HIV/AIDS, Ebola, avianinfluenza,NipahandHendra,SARS,therecentCOVID-19,andothers. A substantial proportion of older human pathogens likely also arose from animals. Thus, animal pathogens can have substantial impact on human health. As is abundantly illustrated in this book, veterinary application is a robusttestinggroundfornewvaccinesandnewvaccinestrategies.Somevirus vectorplatforms,suchascertainpoxvirusesandreplication-defectiveadeno- virus, are gaining substantial evaluation in both veterinary and human use. Theincreasedavailabilityofhighlycharacterizedvectorplatformswithclini- cal experience will facilitate and expedite their use for additional pathogens including newly emerging pathogens such as COVID-19. Some viral vector vaccines likely will be able to be used in both animals and humans. When feasible, vaccinationofanimals tocontrolpathogenswithzoonoticpotential shouldreducetransmission(e.g.,rabies).Thus,vaccinesagainstpathogensof animal origin, and the use of the virus vector vaccine strategy, will be of increasing importance given the increasing threat to humans from animal pathogens. Veterinaryvaccinedevelopmentisacomplexandfascinatingfieldofstudy because of the wide range of vaccine target species, target pathogens, and potentialvaccines.Asdescribedinthisbook,thereisasubstantialnumberof commercial veterinary vaccines based on the viral vector vaccine strategy (also, see Ref. [1]). These include at least 13 commercial poxvirus-based vaccines targeting nine different pathogens (including rabies, canine viii Foreword distemper, and a poultry mycoplasma; chapter “Poxvirus Vectors”), several herpesvirus-basedvaccinestargetingatleastfivedifferentpathogens(includ- ing Marek’s disease, avian influenza, and infectious bursal disease; chapter “The Construction and Evaluation of Herpesvirus Vectors”), adenovirus- based rabies and foot-and-mouth disease vaccines (chapter “Adenovirus Vectors”), and others. We are still exploring the potential of the available vectors. A number of vectors have been improved by years of optimization. Continuing advances in the tools and understanding of molecular biology, pathogen-hostinteractions,andimmunobiologywillfacilitatefutureincreases in the number and effectiveness of viral vector vaccines. This timely book givesavaluableoverviewofthestateoftheart. NationalInstituteofAllergyandInfectiousDiseases PeterL.Collins NationalInstituteofHealth Bethesda,Maryland,USA e-mail:[email protected] References 1. Current Veterinary Biologics Product Catalog – USDA APHIS. https:// www.aphis.usda.gov/aphis/ourfocus/animalhealth/veterinary-biologics/ CT_Vb_licensed_products 2. DeFiletteM,UlbertS,DiamondM,SandersNN.RecentprogressinWest Nile virus diagnosis and vaccination. Vet Res. 2012;43(16). http://www. veterinaryresearch.org/content/43/1/16 3. Desmettre P, Languet B, Chappuis G, Brochier B, Thomas I, Lecocq JP, KienyM-P,BlancouJ,AubertM,ArtoisM,PastoretP-P.Useofvaccinia rabies recombinant for oral vaccination of wildlife. Vet Microbiol. 1990;23:227–36. 4. KienyMP,LatheR,DrillenR,SpehnerD,SkoryS,SchmittD,WiktorT, Kaprowski H, Lecocq JP. Expression of rabies virus glycoprotein from a recombinantvacciniavirus.Nature.1984;322:163–6. 5. Smith GL, Murphy BR, Moss B. Construction and characterization of an infectiousvacciniavirusrecombinantthatexpressestheinfluenzahemag- glutinin gene and induces resistance to influenza virus infection in hamsters.ProcNatlAcadSciUSA.1983;80:7155–9. Contents PartI FundamentalsofViralVectorVaccineDevelopment IntroductiontoVeterinaryVaccines. . . . . . . . . . . . . . . . . . . . . . . 3 TeshomeMebatsion WhatIsRequiredtoDevelopaViralVectorVaccine:Key ComponentsofVaccine-InducedImmuneResponses. . . . . . . . . . 13 PhilipJ.Griebel VirusesandtheEvolutionofViralVectors. . . . . . . . . . . . . . . . . . 21 CarlaGilesandThiruVanniasinkam TheRoleofAdjuvantsintheApplicationofViralVector Vaccines. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 TimothyJ.Mahony PartII DNAVirusVectors AdenovirusVectors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 LisaneworkE.Ayalew,AmitGaba,WenxiuWang, andSureshK.Tikoo PoxvirusVectors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 LokR.JoshiandDiegoG.Diel TheConstructionandEvaluationofHerpesvirusVectors. . . . . . . 95 K.E.RobinsonandT.J.Mahony PartIII RNAVirusVectors ParamyxovirusesasVaccineVectors. . . . . . . . . . . . . . . . . . . . . . . 113 SibaK.Samal RhabdovirusesasVaccineVectorsforVeterinaryPathogens. . . . 141 GertZimmer CoronavirusesasVaccineVectorsforVeterinaryPathogens. . . . . 149 DingXiangLiu,YanLingNg,andToSingFung Alphavirus-BasedVaccines. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169 KennethLundstrom ix x Contents PartIV ApplicationofViralVectorVaccines,Challenges andFutureDirections ManufacturingandControlofViralVectoredVaccines: Challenges. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183 ZahiaHannas,JoannaSookMunTan,YangZhang, FredericLhermitte,CatherineCleuziat,LauriMotes-Kreimeyer, PhilippeDhoms,andMichelBublot RegulatoryStrategiesandFactorsAffectingVeterinaryViral VectorDevelopment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201 MichelBublot,VirginieWoerly,QinghuaWang,andHallieKing EmergingViral-VectoredTechnology:FuturePotential ofCapripoxvirusandAfricanSwineFeverVirusasViral Vectors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217 ShawnBabiuk
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