Assessment of the Immunogenicity and Protective Aspects of a DNA Vaccine Targeting Crimean Congo Hemorrhagic Fever Virus Glycoprotein Gc

Year 2021, Volume: 23 Issue: 1, 66 - 75, 30.04.2021

Ergin Sahin , Arzu Çöleri Cihan , Touraj Aligholipour , Katalin Foldes , Evren Doruk Engin , Aykut Özkul

https://doi.org/10.18678/dtfd.864114

Cited By: 3

Abstract

Aim: Crimean Congo Hemorrhagic Fever (CCHF) is a lethal, endemic infectious disease in human. For the preventive measures of the disease, there is currently no safe and efficient vaccine, widely for human use. Vaccine development for CCHF virus is an actively researched subject. In this study, we aimed to investigate the immunizing and protective potentials of the CCHF virus surface glycoprotein Gc that is delivered as a single antigen via a DNA based vaccine vector.
Material and Methods: A DNA based vaccine targeting the immunogenic envelope glycoprotein Gc of a CCHF virus isolate with Turkey origin (Ank2) was generated and its immunogenicity and protective capability against lethal challenge in IFNα/βR-/- receptor knock out mice was assessed.
Results: The developed vaccine candidate (pGc) elicited a considerable amount of neutralizing antibody responses in the vaccinated mice. The vaccine candidate significantly induced both antiviral Th1 and B cell activating Th2 immune responses deduced from the cytokine production profiles in the vaccinated mice. However, despite the immune responses elicited post-immunization, the vaccine failed to confer protection against lethal CCHF virus infection.
Conclusion: To the best of our knowledge, this is the first report of a DNA vaccine candidate generated against CCHF virus based on the glycoprotein Gc. The pGc vaccine candidate exhibited antigen-specific immunity in IFN/α/βR-/- mice, but was unable to produce a protection upon lethal challenge with the homologous CCHF virus. Once we comprehensively understand the immune correlates of protection, we will be more eligible to significantly improve the efficacy of vaccines.

Keywords

Crimean Congo Hemorrhagic Fever Virus, DNA Vaccine, Immune Responses, Lethal Challenge

Supporting Institution

Tubitak

Project Number

115S074

Thanks

This research study was partially funded by The Scientific and Technological Research Council of Turkey (TUBITAK) under the 1003-Primary Subjects R&D Funding Program with the project number of 115S074. Part of this study was orally presented by the first author Ergin Sahin in the 2nd International Conference on Crimean Congo Hemorrhagic Fever which was held in Thessaloniki/Greece on the 10th–12th of September 2017 (PMID: 29199036).

Kırım Kongo Kanamalı Ateşi Virüsü Glikoprotein Gc’yi Hedef Alan Bir DNA Aşısının Bağışıklık ve Koruyuculuk Sağlama Özelliklerinin Değerlendirilmesi

Abstract

Amaç: Kırım Kongo Kanamalı Ateşi (KKKA), insanda ölümcül, endemik bir enfeksiyon hastalığıdır. Hastalığın önleyici tedbirleri için şu anda insanlarda yaygın olarak kullanılmak üzere güvenli ve etkili bir aşı bulunmamaktadır. KKKA virüsü için aşı geliştirilmesi, aktif olarak araştırılan bir konudur. Bu çalışmada, DNA esaslı bir aşı vektörü ile tek bir antijen olarak verilen KKKA virüsü yüzey glikoproteini Gc'nin bağışıklık kazandırıcı ve koruyucu potansiyellerinin araştırılması amaçlanmıştır.
Gereç ve Yöntemler: Türkiye menşeli (Ank2) bir KKKA virüs izolatının immünojenik özellikteki zarf glikoproteini Gc'yi hedefleyen DNA esaslı bir aşı oluşturulmuş ve bu aşı adayının immünojenisitesi ve aşılanmış IFNα/βR-/- farelerde öldürücü doza karşı koruyucu yeteneği değerlendirilmiştir.
Bulgular: Geliştirilen aşı adayı (pGc), aşılanmış farelerde önemli miktarda nötralize edici antikor yanıtı ortaya çıkardı. Aşı adayı, aşılanmış farelerde hem antiviral Th1, hem de B hücresini aktive eden Th2 bağışıklık tepkilerini önemli ölçüde uyardı. Bununla birlikte, aşılama sonrasında ortaya çıkan bağışıklık yanıtlarına rağmen, aşı, ölümcül KKKA virüsü enfeksiyonuna karşı koruma sağlayamadı.
Sonuç: Bildiğimiz kadarıyla bu çalışma, glikoprotein Gc'yi hedef alan KKKA virüsüne karşı oluşturulan bir DNA aşı adayının ilk raporudur. PGc aşı adayı, IFNα/βR-/- farelerde antijene özgü bağışıklık yanıtı oluşturdu, ancak ölümcül dozdaki homolog KKKA virüsüne karşı bir koruma üretemedi. Aşı aracılı korunmanın bağışıklık ile olan ilişkilerini daha detaylı olarak anladığımızda, aşıların etkinliğini önemli ölçüde iyileştirme kabiliyetine sahip olacağız.

Keywords

Kırım Kongo kanamalı ateşi virüsü, DNA aşısı, İmmün yanıt, Ölümcül sınama

Project Number

115S074

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