Vaccine Platform Comparison: Protective Efficacy against Lethal Marburg Virus Challenge in the Hamster Model

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.

Keywords: ChAdOx; Fc effector function; MARV; VSV; antibody; repRNA/LION; replicating RNA; vesicular stomatitis virus.

Figure 1

VSV-MARV and LION-MARV completely protect hamsters from lethal challenge. Hamsters were vaccinated with a single intramuscular dose of VSV-MARV, LION-MARV, ChAdOx-MARV, or kept naïve (Control). (A) Survival and (B) body weight changes during the acute phase of the disease are shown. MARV viremia and tissue viral loads were assessed by (C) RT-qPCR and (D) viral titration. Geometric mean and geometric SD are depicted in (C,D). Statistical significance of survival was determined by Mantel–Cox test, other data were evaluated by Kruskal–Wallis test with Dunn’s multiple comparisons. Statistical significance is indicated where achieved as p < 0.001 (***), p < 0.01 (**), and p < 0.05 (*). TCID₅₀, median tissue culture infectious dose.

Figure 2

ChAdOx-MARV-vaccinated hamsters demonstrate a protective and pathogenic cytokine profile. Groups of hamsters were vaccinated with a single dose of VSV-MARV, LION-MARV, ChAdOx-MARV, or kept naïve (Control). The serum profiles of selected hamster cytokines including (A) IFNγ, (B) IL-6, (C) MIP-1α and (D) MCP-1 were assessed in the acute (day 5) and convalescent (day 28) phase of disease. Mean and standard error of the mean are depicted. Statistical significance was evaluated by Kruskal–Wallis test with Dunn’s multiple comparisons. Statistical significance is indicated where achieved as p < 0.01 (**), and p < 0.05 (*).

Figure 3

Vaccine platform impacts the humoral response functionality profile. (A) MARV GP-specific IgG titers in serum. Functionality of the antigen-specific humoral responses assessed by (B) 50% neutralization (NT₅₀), (C) antibody-dependent cellular phagocytosis (ADCP), (D) antibody-dependent neutrophil phagocytosis (ADNP), and (E) antibody-dependent complement deposition (ADCD) in serum. Geometric mean and geometric SD are depicted in (A,B,E); mean with SEM is depicted in (C,D). Statistical significance was evaluated by Kruskal–Wallis test with Dunn’s multiple comparisons. Statistical significance is indicated where achieved as p < 0.01 (**) and p < 0.05 (*).