Systematic review of Marburg virus vaccine nonhuman primate studies and human clinical trials

Dulin, Nicholas; Spanier, Adam J.; Merino, Kristen M.; Hutter, Jack; Waterman, Paige; Lee, Christine; Hamer, Melinda

doi:10.1016/j.vaccine.2020.11.042

Cited by 37 publications

(49 citation statements)

References 40 publications

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“…The dynamics of MARV GP-specific IgM and IgG responses demonstrated here were very similar to those reported for VSV-EBOV peaking around 10-14 days post vaccination ( 12 ). Although VSV-EBOV induced neutralizing IgM antibodies in humans ( 25 ), neutralizing antibody responses were not examined here as previous studies showed that they do not correlate with outcome after MARV infection ( 26 ). The development of the antibody response correlates with the induction of genes important for lymphocyte activation and function 11 and 14 DPV.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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Marburg virus (MARV) is a member of the filovirus family that causes hemorrhagic disease with high case fatality rates. MARV is on the priority list of the World Health Organization for countermeasure development highlighting its potential impact on global public health. We developed a vesicular stomatitis virus (VSV)-based vaccine expressing the MARV glycoprotein (VSV-MARV) and previously demonstrated uniform protection of nonhuman primates (NHPs) with a single dose. Here, we investigated the fast-acting potential of this vaccine by challenging NHPs with MARV 14, 7 or 3 days after a single dose vaccination with VSV-MARV. We found that 100% of the animals survived when vaccinated 7 or 14 days and 75% of the animal survived when vaccinated 3 days prior to lethal MARV challenge. Transcriptional analysis of whole blood samples indicated activation of B cells and antiviral defense after VSV-MARV vaccination. In the day -14 and -7 groups, limited transcriptional changes after challenge were observed with the exception of day 9 post-challenge in the day -7 group where we detected gene expression profiles indicative of a recall response. In the day -3 group, transcriptional analysis of samples from surviving NHPs revealed strong innate immune activation. In contrast, the animal that succumbed to disease in this group lacked signatures of antiviral immunity. In summary, our data demonstrate that the VSV-MARV is a fast-acting vaccine suitable for the use in emergency situations like disease outbreaks in Africa.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…Moreover, past instances of travelers returning home with MVD demonstrate the possibility of international spread [ 33 , 34 ]. While many experimental MARV vaccines have been developed over the last several years, only a few candidates have been evaluated in small Phase I clinical trials and none have been approved for use in humans [ 8 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

A Cloned Recombinant Vesicular Stomatitis Virus-Vectored Marburg Vaccine, PHV01, Protects Guinea Pigs from Lethal Marburg Virus Disease

et al. 2022

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Marburg virus (MARV) is a negative-sense, single-stranded RNA virus that belongs to the Filoviridae family. Despite having caused numerous outbreaks of severe hemorrhagic fever with high case fatality rates, there are still no clinically approved therapeutics or vaccines to treat or prevent MARV disease. Recombinant vesicular stomatitis viruses (rVSVs) expressing heterologous viral glycoproteins have shown remarkable promise as live-attenuated vaccine vectors, with an rVSV-based Ebola virus vaccine having received regulatory approval in the United States and numerous other countries. Analogous rVSV vaccine vectors have also been developed for MARV and have shown efficacy in several preclinical studies conducted in nonhuman primates. Here, we used a guinea pig model to confirm the protective efficacy of a cloned, rVSV-based candidate vaccine, termed PHV01, expressing the MARV variant Angola glycoprotein. Our results demonstrated that a single dose (2 × 106 PFU) of vaccine administered 28 days prior to challenge with a uniformly lethal dose of guinea-pig-adapted MARV variant Angola provided complete protection from death and disease. Moreover, protection was robust, with as little as 200 PFU of vaccine conferring significant protection. Not only does this study highlight the potential predictive value of the guinea pig model in the evaluation of MARV countermeasures, but it also demonstrates consistent and reproducible protection afforded by a clonal vaccine candidate. Indeed, this study identifies PHV01 as a suitable vaccine candidate for advanced development.

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“…Numerous experiments were conducted on rodent and NHP models for testing vaccine efficacies against MARV. To date, some vaccines have been trialed for human use [ 78 , 181 , 182 ]. Among them, cAd3 vaccine, also known as chimpanzee adenovirus serotype 3 vector, encoded with wild type GP from MARV, is in phase 1 clinical trial for human use [ 183 ].…”

Section: Management Approaches For Marburg Virusmentioning

confidence: 99%

Pathogenicity and virulence of Marburg virus

et al. 2022

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Marburg virus (MARV) has been a major concern since 1967, with two major outbreaks occurring in 1998 and 2004. Infection from MARV results in severe hemorrhagic fever, causing organ dysfunction and death. Exposure to fruit bats in caves and mines, and human-to-human transmission had major roles in the amplification of MARV outbreaks in African countries. The high fatality rate of up to 90% demands the broad study of MARV diseases (MVD) that correspond with MARV infection. Since large outbreaks are rare for MARV, clinical investigations are often inadequate for providing the substantial data necessary to determine the treatment of MARV disease. Therefore, an overall review may contribute to minimizing the limitations associated with future medical research and improve the clinical management of MVD. In this review, we sought to analyze and amalgamate significant information regarding MARV disease epidemics, pathophysiology, and management approaches to provide a better understanding of this deadly virus and the associated infection.

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Systematic review of Marburg virus vaccine nonhuman primate studies and human clinical trials

Cited by 37 publications

References 40 publications

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

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

A Cloned Recombinant Vesicular Stomatitis Virus-Vectored Marburg Vaccine, PHV01, Protects Guinea Pigs from Lethal Marburg Virus Disease

Pathogenicity and virulence of Marburg virus

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