KSHV Subunit Vaccine Candidates to Elicit Potent Humoral Immune Reponses against KSHV Infection
KSHV 亚单位候选疫苗可引发针对 KSHV 感染的有效体液免疫反应
基本信息
- 批准号:10376277
- 负责人:
- 金额:$ 85.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-03-22 至 2026-02-28
- 项目状态:未结题
- 来源:
- 关键词:AIDS/HIV problemAdultAnimal ModelAnimalsAntibodiesAntibody ResponseAntibody titer measurementB-Cell LymphomasB-LymphocytesCD34 geneCallithrixCallithrix jacchus jacchusCarcinogensCellsChildDataDeveloped CountriesDeveloping CountriesDevelopmentDiseaseDoseEndotheliumEnzyme-Linked Immunosorbent AssayEpithelialFK506FibroblastsFundingFutureGlycoproteinsGoalsHerpesviridaeHerpesviridae InfectionsHerpesvirus VaccinesHumanHuman Herpesvirus 8IatrogenesisImmuneImmune responseImmunizationImmunizeImmunocompetentImmunocompromised HostImmunoglobulin GImmunosuppressionIn VitroIncidenceIndividualInfectionInternational Agency for Research on CancerKaposi SarcomaMalignant NeoplasmsMeasuresMediatingMembrane GlycoproteinsModelingModified Vaccinia Virus AnkaraMonkeysMusMyeloid CellsOncogenicOryctolagus cuniculusOutcomePatternPersonsPhase I Clinical TrialsPolyvalent VaccinePopulationPreventive vaccinePrimary InfectionPropertyRegimenResearchRouteSafetySalivaSeroprevalencesSubunit VaccinesT-LymphocyteTacrolimusTestingTimeTransplant RecipientsUnited States National Institutes of HealthVaccinatedVaccinationVaccinesViralViral ProteinsViremiaVirus DiseasesVirus-like particleWild Type Mousebasecancer preventioncell typedesignearly childhoodhumanized mouseimmunogenicimmunogenicityimmunological statusimmunosuppressedin vivoinnovationneutralizing antibodynonhuman primatenovel vaccinespermissivenessplacebo grouppre-clinicalpreventprimary effusion lymphomaprophylacticresponsesuccessvaccine candidatevaccine developmentvaccine evaluationvector
项目摘要
PROJECT SUMMARY
Kaposi sarcoma-associated herpesvirus (KSHV) has been classified as a direct carcinogen by the International
Agency for Research on Cancer because of its ability to cause Kaposi sarcoma (KS) and two rare types of
B-cell lymphoma. KS frequently occurs among iatrogenic or HIV/AIDS-induced immunosuppressed individuals.
To date, there is no licensed KSHV vaccine that can prevent primary infection and subsequent malignancies.
Our objective in this application is to optimize the inclusion of key KSHV glycoproteins (gps), which are
involved in epithelial, endothelial, fibroblast and B-cell entry, into multivalent subunit vaccine candidates that
can stimulate neutralizing antibody (nAb) immune responses to prevent or limit KSHV infection and KSHV+
cancers in vivo. This application builds on my recently completed NCI K01 CA184388-05 research on KSHV
entry mechanisms and vaccine development. Recently, we showed that in vitro, the KSHV glycoprotein gH is
essential for viral infection of epithelial, endothelial, and fibroblasts cells, but not B cells. Notably, we and other
have also shown that both monoclonal and polyclonal Abs to KSHV glycoproteins K8.1, gB, and gH/gL can
neutralize KSHV infection of diverse permissive human cells in vitro. Building on this success, we have
generated quadrivalent virus-like particles (KSHV-LPs) incorporating the four glycoproteins critical for viral
entry (K8.1, gB and gH/gL). In this application we will use wild-type and humanized mice and common
marmoset (Callithrix jacchus) models to test the hypothesis that purified KSHV-LPs delivered directly or
through immunization with a modified vaccinia Ankara vector (MVA-KSHV-LPs) will elicit robust protective nAb
responses to KSHV infection and its associated malignancies. The premise of our proposal is built on strong
evidence that 1) infection with KSHV does not occur during early childhood, as is typical for other
herpesviruses, opening a window of opportunity for vaccination and 2) Abs against the KSHV glycoproteins
K8.1, gB, and gH/gL can neutralize KSHV infection. Furthermore, the permissiveness of humanized mice and
marmosets to KSHV infection offers an ideal platform to test candidate vaccines. Thus, a polyvalent vaccine
that induces prophylactic neutralizing Abs responses will not only be an invaluable candidate vaccine in
preventing KSHV infection, but also of utmost importance in preventing KSHV-associated diseases. We will
provide evidence for the safety of our candidate KSHV vaccine based on three pre-clinical animal models as
prerequisite data for an IND application for a phase I clinical trial. In the long term, the success of our approach
will introduce a new vaccine to the market with a potential for reducing global incidence of KSHV+
malignancies (>44,000 cases/year), and the possibility of limiting KSHV infection and associated malignancies
in developing countries or eradicating them from developed countries where KSHV seroprevalence is <10%.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Javier Gordon Ogembo其他文献
Correction: HPV genotyping by L1 amplicon sequencing of archived invasive cervical cancer samples: a pilot study
- DOI:
10.1186/s13027-024-00589-0 - 发表时间:
2024-06-19 - 期刊:
- 影响因子:2.800
- 作者:
Charles D. Warden;Preetam Cholli;Hanjun Qin;Chao Guo;Yafan Wang;Chetan Kancharla;Angelique M. Russell;Sylvana Salvatierra;Lorraine Z. Mutsvunguma;Kerin K. Higa;Xiwei Wu;Sharon Wilczynski;Raju Pillai;Javier Gordon Ogembo - 通讯作者:
Javier Gordon Ogembo
Javier Gordon Ogembo的其他文献
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{{ truncateString('Javier Gordon Ogembo', 18)}}的其他基金
Unmasking the roles of viral glycoproteins in oral transmission of KSHV
揭示病毒糖蛋白在 KSHV 口腔传播中的作用
- 批准号:
10623087 - 财政年份:2021
- 资助金额:
$ 85.8万 - 项目类别:
Unmasking the roles of viral glycoproteins in oral transmission of KSHV
揭示病毒糖蛋白在 KSHV 口腔传播中的作用
- 批准号:
10474478 - 财政年份:2021
- 资助金额:
$ 85.8万 - 项目类别:
Unmasking the roles of viral glycoproteins in oral transmission of KSHV
揭示病毒糖蛋白在 KSHV 口腔传播中的作用
- 批准号:
10318876 - 财政年份:2021
- 资助金额:
$ 85.8万 - 项目类别:
KSHV Subunit Vaccine Candidates to Elicit Potent Humoral Immune Reponses against KSHV Infection
KSHV 亚单位候选疫苗可引发针对 KSHV 感染的有效体液免疫反应
- 批准号:
10559659 - 财政年份:2021
- 资助金额:
$ 85.8万 - 项目类别:
Unmasking the roles of viral glycoproteins in oral transmission of KSHV
揭示病毒糖蛋白在 KSHV 口腔传播中的作用
- 批准号:
10737872 - 财政年份:2021
- 资助金额:
$ 85.8万 - 项目类别:
Unmasking the roles of viral glycoproteins in oral transmission of KSHV
揭示病毒糖蛋白在 KSHV 口腔传播中的作用
- 批准号:
10627167 - 财政年份:2021
- 资助金额:
$ 85.8万 - 项目类别:
Unmasking the roles of viral glycoproteins in oral transmission of KSHV
揭示病毒糖蛋白在 KSHV 口腔传播中的作用
- 批准号:
10599690 - 财政年份:2021
- 资助金额:
$ 85.8万 - 项目类别:
A multivalent prophylactic and therapeutic vaccine against EBV infection and EBV-associated malignancies
针对 EBV 感染和 EBV 相关恶性肿瘤的多价预防性和治疗性疫苗
- 批准号:
10247243 - 财政年份:2020
- 资助金额:
$ 85.8万 - 项目类别:
Characterization of Epstein-Barr virus monoclonal antibodies as tools for diagnosing and prevention of EBV infection in transplant settings
EB 病毒单克隆抗体作为移植环境中诊断和预防 EBV 感染工具的表征
- 批准号:
9797160 - 财政年份:2018
- 资助金额:
$ 85.8万 - 项目类别:
A novel VLP vaccine to prevent EBV infection and EBV - associated malignancies
一种预防 EBV 感染和 EBV 相关恶性肿瘤的新型 VLP 疫苗
- 批准号:
9302981 - 财政年份:2017
- 资助金额:
$ 85.8万 - 项目类别:
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