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Published on: October 7, 2011
Vaccine Platform Comparison: Protective Efficacy against Lethal Marburg Virus Challenge in the Hamster Model
Kyle L O'Donnell1, Corey W Henderson1, Hanna Anhalt1
1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Abstract:
Marburg virus (MARV), a filovirus, was first identified in 1967 in Marburg, Germany, and Belgrade, former Yugoslavia. Since then, MARV has caused sporadic outbreaks of human disease with high case fatality rates in parts of Africa, with the largest outbreak occurring in 2004/05 in Angola. From 2021 to 2023, MARV outbreaks occurred in Guinea, Ghana, New Guinea, and Tanzania, emphasizing the expansion of its endemic area into new geographical regions. There are currently no approved vaccines or therapeutics targeting MARV, but several vaccine candidates have shown promise in preclinical studies. We compared three vaccine platforms simultaneously by vaccinating hamsters with either a single dose of an adenovirus-based (ChAdOx-1 MARV) vaccine, an alphavirus replicon-based RNA (LION-MARV) vaccine, or a recombinant vesicular stomatitis virus-based (VSV-MARV) vaccine, all expressing the MARV glycoprotein as the antigen. Lethal challenge with hamster-adapted MARV 4 weeks after vaccination resulted in uniform protection of the VSV-MARV and LION-MARV groups and 83% of the ChAdOx-1 MARV group. Assessment of the antigen-specific humoral response and its functionality revealed vaccine-platform-dependent differences, particularly in the Fc effector functions.
Insights
Three Marburg virus (MARV) vaccine platforms were compared in hamsters. The adenovirus-based, RNA replicon, and recombinant vesicular stomatitis virus vaccines showed varying protection levels against MARV. The VSV-MARV and LION-MARV vaccines provided uniform protection.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Marburg virus (MARV), a filovirus, causes sporadic outbreaks with high fatality rates.
- MARV outbreaks have expanded geographically, highlighting the urgent need for effective vaccines.
- No approved vaccines or therapeutics currently exist for MARV.
Purpose of the Study:
- To compare the efficacy of three distinct vaccine platforms against Marburg virus.
- To evaluate adenovirus-based (ChAdOx-1 MARV), RNA replicon-based (LION-MARV), and recombinant vesicular stomatitis virus-based (VSV-MARV) vaccines.
- To assess vaccine-induced humoral immune responses and Fc effector functions.
Main Methods:
- Hamsters were vaccinated with a single dose of ChAdOx-1 MARV, LION-MARV, or VSV-MARV vaccine.
- Vaccinated hamsters were challenged with a lethal dose of hamster-adapted MARV four weeks post-vaccination.
- Antigen-specific humoral responses, including Fc effector functions, were analyzed.
Main Results:
- Uniform protection was observed in hamsters vaccinated with VSV-MARV and LION-MARV.
- The ChAdOx-1 MARV vaccine provided 83% protection against lethal MARV challenge.
- Significant differences in antigen-specific humoral responses and Fc effector functions were noted between vaccine platforms.
Conclusions:
- Both VSV-MARV and LION-MARV vaccines demonstrate strong protective efficacy against Marburg virus in a preclinical model.
- The choice of vaccine platform influences the resulting immune response, particularly Fc effector functions.
- Further development of these promising vaccine candidates is warranted for Marburg virus disease prevention.
