Virulence of Marburg Virus Angola Compared to Mt. Elgon (Musoke) in Macaques: A Pooled Survival Analysis

Abstract

Angola variant (MARV/Ang) has replaced Mt. Elgon variant Musoke isolate (MARV/MtE-Mus) as the consensus standard variant for Marburg virus research and is regarded as causing a more aggressive phenotype of disease in animal models; however, there is a dearth of published evidence supporting the higher virulence of MARV/Ang. In this retrospective study, we used data pooled from eight separate studies in nonhuman primates experimentally exposed with either 1000 pfu intramuscular (IM) MARV/Ang or MARV/MtE-Mus between 2012 and 2017 at the United States Army Medical Research Institute of Infectious Diseases (USAMRIID). Multivariable Cox proportional hazards regression was used to evaluate the association of variant type with time to death, the development of anorexia, rash, viremia, and 10 select clinical laboratory values. A total of 47 cynomolgus monkeys were included, of which 18 were exposed to MARV/Ang in three separate studies and 29 to MARV/MtE-Mus in five studies. Following universally fatal Marburg virus exposure, compared to MARV/MtE-Mus, MARV/Ang was associated with an increased risk of death (HR = 22.10; 95% CI: 7.08, 68.93), rash (HR = 5.87; 95% CI: 2.76, 12.51) and loss of appetite (HR = 35.10; 95% CI: 7.60, 162.18). Our data demonstrate an increased virulence of MARV/Ang compared to MARV/MtE-Mus variant in the 1000 pfu IM cynomolgus macaque model.

Isolation of Angola-like Marburg virus from Egyptian rousette bats from West Africa

“…A direct link to MARV spillover from bats was not made during the event in Angola. Consistent with the high CFR during the outbreak in Angola, the MARV Angola strain appears to be significantly more virulent than all other MARV strains (Musoke, Ravn, and Ozolin) in experimentally infected non-human primates 7,8 . The Angola outbreak was the only MVD outbreak to originate outside of East Africa; all previous MVD outbreaks occurred in, or originated from, Uganda, Kenya, Democratic Republic of the Congo (DRC), or South Africa ex Zimbabwe 9,10 .…”

Single Dose of a VSV-Based Vaccine Rapidly Protects Macaques From Marburg Virus Disease

“…Interestingly, this induction was less robust than that observed for VSV-EBOV as indicated by data presented here and published elsewhere (29)(30)(31). In contrast, antiviral innate immune responses in control animals and those that succumb to infection are progressively amplified as disease progresses and are associated with adverse outcomes and high mortality both in NHP and humans (3,4,16,(32)(33)(34)(35). Although circulating levels of type I IFN do not significantly change with VSV-based vaccination, it is possible that the local production of IFNa/b in draining lymph nodes is sufficient to induce substantial expression of these ISGs (36).…”

Modified vaccinia Ankara vaccine expressing Marburg virus-like particles protects guinea pigs from lethal Marburg virus infection

“…The Angola strain was responsible for the largest outbreak ever documented for MARV, which resulted in 227 deaths out of 252 total cases (a 90% mortality rate) in Uige, Angola 23 . Moreover, the Angola strain was also shown to be more virulent in nonhuman primates than the Musoke strain 24 . GP from the Angola strain differs from that of the Musoke strain by 7.20% 23 ; thus, the study we performed represents the most stringent efficacy test for a MARV vaccine.…”