Title : Robust protection against monkeypox virus mediated by a novel cell-line–Derived MVA vaccine (TG-MVAᴄʟ)
Abstract:
Monkeypox (mpox) is a zoonotic disease caused by the Monkeypox virus (MPXV). Recent global outbreaks in non-endemic countries demonstrated their significance as a threat to public health. The main approved and widely used vaccine to fight MPXV infection, MVA-BN®, is based on the modified vaccinia Ankara (MVA) produced on primary cells (chicken embryo fibroblast - CEF). To respond to the critical and unmet need for vaccine stockpiling preparedness, we have used an easily scalable and transposable cell line-based manufacturing process to produce a novel generation of MVA-based mpox vaccine, the TG-MVACL manufactured on cell line. Safety, immunogenicity (specific of vaccinia virus (VACV) and/or MPXV and prophylactic protection against MPXV clade Ia lethal infection studies) were carried out in mice and non-human primates (NHP) to compare both cell-line manufactured TG-MVACL and its counterpart produced in CEF (TG-MVACEF) with MVA-BN®.
VACV-specific responses were analyzed in BALB/C mice in which all three vaccines developed similar levels neutralizing antibodies (Nab), specific T-cells by ELISPOT which were detected in 70-100% of vaccines.
Stringent, infectious challenge was applied using the MPXV clade Ia (Zaïre 79 strain) in established mice and NHP models. The three vaccines induced very high, comparable protection in CAST/Ei mice (100%) and NHP (88%) in contrast to control groups displaying 100% mortality. Whether in mice or NHP, both the kinetics and level of transient weight loss observed post-challenge, were similar for all vaccine groups.
In the NHP prophylactic model, only a limited number of lesions (< 42) were observed in the vaccines versus up to 400 in control animals indicating that vaccination strongly protected against mpox-induced lesion development and substantially blunted the severity of clinical skin disease following challenge. Following MPXV intratracheal challenge, controls developed rapid and high-magnitude viremia. In contrast, all vaccinated cohorts exhibited markedly attenuated systemic viral burden in the blood and in throat swabs. At immunogenicity peak (D42), all vaccinated animals demonstrated broad vaccine-induced binding antibody responses against both major VACV and MPXV antigens tested. Moreover, neutralizing antibody responses against VACV, MPXV Clade II, and to a lesser extent to MPXV Clade I were also detected in the vaccinated animal. ELISPOT data showed detection of an overall peptide pool with specific response in 30-70 % of the vaccinees.
Overall safety based on clinical signs, local reactogenicity, hematology and biochemistry were good with comparable safety profile across the three MVA-based vaccines, regardless of the manufacturing process.
In conclusion, TG-MVA produced on a continuous cell line (TG-MVACL) or on CEF (TG-MVACEF) induced robust humoral and cellular immune responses, comparable to those elicited by MVA-BN®. Prophylactic protection and safety of TG-MVACL strongly support its clinical development in the fight against MPXV and more broadly against Orthopoxviruses.
