Accelerated DNA vaccine regimen provides protection against Crimean-Congo hemorrhagic fever virus challenge in a macaque model

• Published in: Molecular therapy 2023-02, Vol.31 (2), p.387-397
• Main Authors: Hawman, David W., Meade-White, Kimberly, Leventhal, Shanna, Appelberg, Sofia, Ahlén, Gustaf, Nikouyan, Negin, Clancy, Chad, Smith, Brian, Hanley, Patrick, Lovaglio, Jamie, Mirazimi, Ali, Sällberg, Matti, Feldmann, Heinz
• Format: Article
• Language: English
• Subjects: Animals; CCHF; correlates of protection; Crimean-Congo hemorrhagic fever; DNA vaccine; Hemorrhagic Fever Virus, Crimean-Congo - genetics; Hemorrhagic Fever, Crimean - diagnosis; Hemorrhagic Fever, Crimean - prevention & control; Macaca; macaque model; Medicin och hälsovetenskap; Original; Vaccination; vaccine; Vaccines, DNA
• ISSN: 1525-0016; 1525-0024; 1525-0024
• DOI: 10.1016/j.ymthe.2022.09.016

Crimean-Congo hemorrhagic fever virus (CCHFV) is widely distributed throughout Africa, the Middle East, Southern Asia, and Southern and Eastern Europe. Spread by Hyalomma ticks or by contact with infected animals, CCHF begins non-specifically but can rapidly progress to severe, sometimes fatal, disease. Due to the non-specific early symptoms and often unrecognized infections, patients often present to healthcare systems exhibiting later stages of disease, when treatment is limited to supportive care. Consequently, simple vaccines are critically needed to protect populations at risk of CCHFV infection. Currently, there are no widely approved vaccines for CCHFV. We have previously reported significant efficacy of a three-dose DNA-based vaccination regimen for CCHFV in cynomolgus macaques (Macaca fasicularis). Here, we show that in cynomolgus macaques, plasmid-expressed CCHFV nucleoprotein (NP) and glycoprotein precursor (GPC) antigens elicit primarily humoral and cellular immunity, respectively. We found that a two-dose vaccination regimen with plasmids expressing the NP and GPC provides significant protection against CCHFV infection. Studies investigating vaccinations with either antigen alone showed that plasmid-expressed NPs could also confer protection. Cumulatively, our data show that this vaccine confers robust protection against CCHFV and suggest that both humoral and cellular immunity contribute to optimal vaccine-mediated protection. [Display omitted] Feldmann and colleagues have evaluated a DNA-based vaccine for Crimean-Congo hemorrhagic fever virus in a non-human primate model and found that two immunizations were sufficient to protect against infection and disease. Protection correlated with a robust, but non-neutralizing, antibody response. These data support continued development of this vaccine candidate.