Recombinant Vesicular Stomatitis Virus–Based Vaccines Against Ebola and Marburg Virus Infections

doi:10.1093/infdis/jir349

J Infect Dis. 2011 November 1; 204(Suppl 3): S1075–S1081.

PMCID: PMC3218670

Copyright © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Recombinant Vesicular Stomatitis Virus–Based Vaccines Against Ebola and Marburg Virus Infections

Thomas W. Geisbert^1,² and Heinz Feldmann^3,^4,⁵

¹Galveston National Laboratory

²Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas

³Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana

⁴National Microbiology Laboratory, Public Health Agency of Canada

⁵Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada

Corresponding author.

Correspondence: Thomas W. Geisbert, PhD, Galveston National Laboratory, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77550-0610 (Email: tom.geisbert/at/utmb.edu).

Potential conflicts of interest: T. W. G. and H. F. claim intellectual property regarding vesicular stomatitis virus–based vaccines for Ebola and Marburg infections.

This article has been cited by other articles in PMC.

Abstract

The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with a high mortality rate in humans and nonhuman primates. Among the most-promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Importantly, a single injection of blended rVSV-based filovirus vaccines was shown to completely protect nonhuman primates against Marburg virus and 3 different species of Ebola virus. These rVSV-based vaccines have also shown utility when administered as a postexposure treatment against filovirus infections, and a rVSV-based Ebola virus vaccine was recently used to treat a potential laboratory exposure. Here, we review the history of rVSV-based vaccines and pivotal animal studies showing their utility in combating Ebola and Marburg virus infections.

Marburg virus (MARV) and Ebola virus (EBOV) are significant human pathogens that present a public health concern as emerging or reemerging viruses and as potential biological weapons. No vaccine or antiviral drug for MARV or EBOV is currently licensed and available for human use. Although Marburg and Ebola hemorrhagic fevers (HF) are rare diseases, a preventive vaccine could be important for several groups, including risk groups during filovirus outbreaks in endemic areas in sub-Saharan Africa (medical personnel, patient care personnel, family members); national and international healthcare workers and outbreak response personnel; laboratory workers conducting research on filoviruses; and military and other service personnel susceptible to filoviruses used as bioweapons. The properties of the filovirus vaccines required by these diverse groups may vary. For example, although laboratory and healthcare workers and some military personnel in stable settings with defined risk may be candidates for a multidose vaccine, outbreak settings require protection that is rapidly conferred with a single administration. The ideal vaccine that meets all needs would, with a single administration, rapidly confer long-term protection with little or no filovirus viremia against all species of EBOV that are pathogenic in humans as well as the diverse strains of MARV.

Remarkable progress has been made over the preceding decade in developing candidate preventive vaccines against filoviruses in nonhuman primate (NHP) models. There are at least 6 different vaccine systems that have shown promise in completely protecting NHPs against EBOV or MARV infection [1–16] (Table 1). Among these prospective vaccines that have shown efficacy in NHP models of filoviral HF, 2 candidates, 1 based on a replication-defective adenovirus serotype 5 and the other on recombinant vesicular stomatitis virus (rVSV), have provided complete protection to NHPs when administered as a single injection. This review focuses on rVSV-based filovirus vaccines.

Table 1.

Most-Promising Vaccine Platforms With Efficacy in Nonhuman Primates

EBOLA AND MARBURG VIRUSES

Marburg virus (MARV) and Ebola virus (EBOV), the causative agents of Marburg and Ebola HF, represent the 2 genera that comprise the family Filoviridae [17, 18]. The Marburgvirus genus contains a single species, Lake Victoria marburgvirus (MARV), whereas the Ebolavirus genus is comprised of 4 recognized species: (1) Sudan ebolavirus (SEBOV), (2) Zaire ebolavirus (ZEBOV), (3) Côte d’Ivoire ebolavirus (also known and here referred to as Ivory Coast ebolavirus (ICEBOV)), and (4) Reston ebolavirus (REBOV). A putative fifth species, Bundigbugyo ebolavirus (BEBOV), was associated with an outbreak in Uganda in 2007 [19]. MARV, ZEBOV, SEBOV, and BEBOV are important human pathogens with case-fatality rates frequently ranging up to 90% for MARV and ZEBOV, and around 55% for SEBOV (reviewed in [18]). Based on a single outbreak, the newly discovered BEBOV appears to be less pathogenic, with a case-fatality rate of about 25% [19]. ICEBOV caused deaths in chimpanzees and a severe nonlethal human infection in a single case in the Republic of Côte d’Ivoire in 1994 [20]. REBOV is lethal for macaques but has not yet been reported to cause disease in humans [18].

EBOV and MARV are filamentous, enveloped, nonsegmented, negative-sense RNA viruses with genomes of approximately 19 kb. Each virus encodes 7 structural gene products in the following order: nucleoprotein (NP), virion protein (VP) 35, VP40, glycoprotein (GP), VP30, VP24, and the polymerase (L). In addition, EBOV expresses at least 1 nonstructural soluble GP (sGP) encoded by the GP gene [17, 18]. The GP, with variable contributions from other viral proteins such as NP, appears to be the key immunogenic protein in vaccine protection.

RECOMBINANT VSV AS A VACCINE VECTOR FOR FILOVIRUSES

VSV is the prototypic member of the family Rhabdoviridae, a family of negative-stranded RNA viruses with a simple genome organization encoding 5 structural proteins in the order nucleocapsid (N), phosphoprotein (P), matrix (M), glycoprotein (G), and an RNA-dependent RNA polymerase (L) [21]. VSV causes a disease in cattle, horses, deer, and pigs that is characterized by vesiculation and ulceration of the tongue, oral tissues, feet, and teats [21]. Infected animals typically recover within 2 weeks. Whereas naturally occurring VSV infection of humans is rare, infections have been reported in persons who were directly exposed to infected livestock, who were living within endemic regions, or who were accidentally exposed in laboratories [22–24]. VSV infection of humans usually either is asymptomatic or causes a mild influenza-like illness [22-24]. Among small animals, mice have shown utility as a model for evaluating VSV pathogenesis. For example, intranasal infection of mice with VSV results in significant weight loss (up to 20% of preinfection body weight) 2–5 days after infection [25, 26]. This weight loss is a convenient measure of VSV pathogenesis. Also, intracerebral inoculation of mice with VSV produces significant neuropathology that has shown utility in neurovirulence assays [27].

Previous studies demonstrated that rhabdoviruses have utility as expression vectors with potential use as viral vaccine vectors [25–32]. Live viral vaccines have traditionally offered the highest level of protection against viral infections. Such vaccines induce strong cellular and humoral host immune responses as a result of the intracellular synthesis of specific antigens at high levels over a prolonged period. In the last few years, Rose and colleagues have pioneered the use of rVSV, the prototypic member of the Rhabdoviridae family, as an expression and vaccine vector [25, 26, 28, 33–35]. Certain characteristics of VSV suggest that rVSVs expressing foreign viral genes would be good vaccine candidates. VSV grows to very high titers in many cell lines in vitro (>10⁹ plaque-forming units [PFU]/mL) and can be propagated in almost all mammalian cells. VSV elicits strong humoral and cellular responses in vivo, and is able to elicit both mucosal and systemic immunity. Additionally, the extremely low percentage of VSV seropositivity in the general population [22–24] and the lack of serious pathogenicity in humans are some of the possible advantages of using rVSV vaccines in humans. Importantly, the single-stranded RNA genome of VSV does not undergo reassortment and therefore lacks the potential to undergo genetic shifts in vivo. Furthermore, VSV replicates within the cytoplasm of infected cells and does not undergo genetic recombination.

More than a decade ago, a procedure for generating replication-competent, negative-stranded rVSV entirely from complementary DNA was established [34]. The genetic flexibility of VSV has allowed the development of rVSVs that express foreign viral proteins to high levels [33, 36]. Several different strategies have been employed in developing candidate replication-competent rVSV-based vaccines, all of which have adopted measures to enhance safety. For example, previous studies have shown that the pathogenesis and neurovirulence of VSV in mice is directly associated with the VSV G [26, 37, 38]. Studies have also shown that the VSV G is the determinant of pathogenesis in swine [39]. To attenuate rVSV vectors, some groups have made mutations truncating the VSV G cytoplasmic domain from 29 to 9 or 1 amino acid. This action resulted in abrogating pathogenesis in mice [26]. Another approach has been to develop GP exchange vectors where the VSV G is completely deleted and replaced with a foreign GP [36].

The generation of rVSVs and their utility in preventing virus infections was shown in several studies. Rose and colleagues demonstrated that live attenuated rVSV expressing the human immunodeficiency virus (HIV) envelope (env) and core (Gag) proteins protected rhesus monkeys from AIDS following challenge with a pathogenic AIDS virus [28]. Similarly, Roberts and coworkers developed rVSV vectors expressing influenza hemagglutinin (HA) protein, which are completely attenuated for pathogenesis in the mouse model [25]. This nonpathogenic vaccine also provided complete protection from lethal influenza virus challenge. Moreover, another vaccine with the VSV G deleted and expressing HA (rVSV [open triangle]

G-HA) was also protective and nonpathogenic, and had the additional advantage of inducing no neutralizing antibody to the vector itself [25]. Importantly, mice immunized with the rVSV [open triangle]

G-HA and subsequently challenged with wild-type VSV develop neutralizing antibody titers to VSV; these antibodies are directed against VSV G. It was subsequently shown that these GP exchange vectors allowed effective boosting and generation of neutralizing antibodies to a primary isolate of HIV type 1 [28]. Together, these studies indicate that rVSV [open triangle]

G is a reusable vector, which is a particularly important advantage in any vaccine platform.

Using the strategy shown for developing nonpathogenic rVSV [open triangle]

G vectors expressing influenza genes, rVSV [open triangle]

G vaccines were developed for EBOV and MARV [4, 12, 40]. The rVSV [open triangle]

G vectors were modified to carry the GP gene from ZEBOV, SEBOV, or the Musoke strain of MARV in place of the VSV G protein. All rVSV [open triangle]

G viruses expressing filovirus GPs exhibited rhabdovirus morphology. Unlike the rVSVs with an additional transcription unit expressing the soluble GPs, the viruses carrying the foreign transmembrane filovirus GPs in replacement of the VSV G were slightly attenuated in growth [40].

RECOMBINANT VSV VECTORS AS PREVENTIVE FILOVIRUS VACCINES

Initial studies using rVSV [open triangle]

G-based filovirus vaccines focused on the ability of these vaccines to protect animals against homologous filovirus challenges. Vaccination of BALB/c mice with a single intraperitoneal injection of as few as 2 PFU of a rVSV [open triangle]

G vector expressing the ZEBOV GP completely protected the animals against a lethal mouse-adapted ZEBOV challenge 28 days after the immunization [41]. Likewise, a single intramuscular vaccination of cynomolgus monkeys with a rVSV [open triangle]

G vector expressing the ZEBOV GP induced strong humoral and cellular immune responses in vaccinated monkeys and elicited complete protection against a high-dose (1000 PFU) intramuscular challenge of homologous ZEBOV given 28 days later [4] (Table 2). However, there was no cross-protection, as subsequent back-challenge of the ZEBOV-surviving macaques with SEBOV resulted in fatal disease [4]. This rVSV [open triangle]

G ZEBOV vaccine was subsequently tested against a high-dose (1000 PFU) aerosol challenge of homologous ZEBOV. A single intramuscular vaccination of cynomolgus monkeys with rVSV [open triangle]

G ZEBOV GP completely protected animals against a homologous aerosol challenge of ZEBOV given 28 days later [9] (Table 2). Furthermore, protection can be conferred by these rVSV [open triangle]

G ZEBOV GP vaccines via various delivery routes; immunization of either BALB/c mice or cynomolgus monkeys with the rVSV [open triangle]

G ZEBOV GP vaccine by either the intranasal or oral route resulted in complete protection of all animals against a high-dose (1000 PFU) intramuscular homologous ZEBOV challenge [13, 41] (Table 2). Robust ZEBOV GP-specific humoral responses and T-cell responses were induced after vaccination and 6 months after ZEBOV challenge in macaques vaccinated by either the intranasal or oral route [13].

Table 2.

Preventive Recombinant Vesicular Stomatitis Virus–Based Ebola and Marburg Virus Vaccines in Nonhuman Primates

For MARV, a single intramuscular vaccination of cynomolgus monkeys with a rVSV [open triangle]

G MARV-Musoke GP vaccine elicited complete protection against a high-dose (1000 PFU) intramuscular challenge of homologous MARV given 28 days later [4] (Table 2). The animals were also protected on rechallenge with a 1967 MARV strain 113 days later [4]. Furthermore, the same vaccine proved protective against the genetically most-disparate MARV strain, Ravn, and what appears to be the most-virulent strain, Angola, suggesting that it may confer cross-protection against all the diverse strains of MARV [5] (Table 2). As with ZEBOV, recent studies showed that a single vaccination of cynomolgus monkeys with rVSV [open triangle]

G MARV-Musoke GP completely protected animals against a homologous aerosol challenge of MARV given 28 days later [9] (Table 2).

Because of possible overlapping endemicities of the filoviruses in Africa, as well as the threat of bioterrorism, it would be ideal to have a single-injection vaccine that could protect against the various species and strains of EBOV and MARV. In a recent study, cynomolgus monkeys were vaccinated with a multivalent blended vaccine consisting of equal parts of the rVSV [open triangle]

G GP vaccines for MARV, EBOV, and SEBOV [12]. At 4 weeks postvaccination, groups of the animals were challenged with MARV, ZEBOV, SEBOV, or ICEBOV (Table 2). None of the vaccinated macaques succumbed to a filovirus challenge, showing great promise with this single-injection, multivalent, blended platform.

RECOMBINANT VSV–BASED FILOVIRUS VACCINES AS TREATMENTS

In addition to its utility as a preventive vaccine, the rVSV [open triangle]

G vaccine platform has also been used as a postexposure treatment for filovirus infections [Table 3]. Treatment of rhesus monkeys with rVSV [open triangle]

G MARV-Musoke GP shortly after a homologous high-dose MARV challenge resulted in complete protection of all animals from clinical illness and death [42]. Subsequent studies demonstrated that the rVSV [open triangle]

G GP vaccines for ZEBOV and SEBOV protected 50% and 100%, respectively, of rhesus macaques when administered as postexposure prophylaxis after high-dose homologous virus challenge [43, 44]. The vaccine was administered in these studies 20–30 minutes after filovirus challenge. A major question is how long after virus exposure can the rVSV [open triangle]

G vaccine be effective? In a recent study, treatment of rhesus monkeys with rVSV [open triangle]

G MARV-Musoke GP 24 hours after homologous MARV challenge resulted in protection of 5 of 6 monkeys, whereas, remarkably, 2 of 6 animals were protected when the vaccine was administered 48 hours after infection [45].

Table 3.

Postexposure Recombinant Vesicular Stomatitis Virus–Based Ebola and Marburg Virus Vaccines in Nonhuman Primates

SAFETY OF RECOMBINANT VSV–BASED FILOVIRUS VACCINES

The main concern with all replication-competent vaccines, including the rVSV [open triangle]

G platform, is their safety, especially in persons with compromised immune systems. However, initial results of various rVSV [open triangle]

G and rVSV vectors in NHPs are promising. No toxicity was seen in rhesus macaques following intranasal inoculation with wild-type VSV, rVSV, and 2 rVSV-HIV vaccines, although significant neurovirulence was noted in 1 of 4 animals after direct intrathalamic inoculation with rVSV [46]. To date, no toxicity has been seen in >80 NHPs given rVSV [open triangle]

G MARV or EBOV vaccines [4, 5, 9, 12, 13, 47]. Furthermore, no significant vaccine shedding has been seen in these experiments despite challenge doses of up to 10⁷ PFU [4, 5, 9, 12, 13, 47] which suggests, along with the natural low transmissibility of VSV [48], that spread to persons outside the vaccine target population is unlikely.

To specifically address safety of the rVSV [open triangle]

G-based filovirus vaccines, the rVSV [open triangle]

G ZEBOV GP vaccine was evaluated in 2 animal models with defective immune systems, nonobese diabetic–severe combined immunodeficient (NOD-SCID) mice [41] and simian/human immunodeficiency (SHIV) –infected rhesus monkeys [47]. On immunization, no evidence of overt illness was noted in any of the animals. In addition, the rVSV [open triangle]

G ZEBOV GP vaccine was recently used to treat a laboratory worker after a recent laboratory accident [49]. The vaccine was administered <48 hours after potential ZEBOV exposure. The patient developed fever, headache, and myalgia 12 hours after injection. No other adverse effects were reported. Because it is not certain that infection actually occurred, efficacy of the vaccine in this case could not be evaluated. To further ensure safety, the VSV G, to which the pathogenicity of wild-type VSV may be attributable [37–39] has been deleted in the rVSV [open triangle]

G filovirus vaccines. Current studies are being performed to evaluate the neurovirulence of the rVSV [open triangle]

G ZEBOV GP and rVSV [open triangle]

G MARV-Musoke vaccines in a conventional intrathalamic neurovirulence assay in cynomolgus monkeys. Regarding possible vaccine virus mutation to more-virulent variants, some comfort can be taken from noting the case of the live measles vaccine that has been in use in the United States and other countries since the 1960s (reviewed in [50]) with no evidence of acquiring a higher pathogenic potential.

SUMMARY

Vaccine development for EBOV and MARV has been successful over the preceding decade and has generated several promising experimental approaches (Table 1). The rVSV platform has shown complete efficacy as a preventive single-shot vaccine in 3 relevant animal models, including the “gold standard” nonhuman primate models. A blended cocktail has shown complete efficacy as a preventive vaccine against all public health relevant filovirus species with partial overlapping endemicity zones in central Africa. Finally, the platform has shown partial to complete efficacy in postexposure treatment against homologous filovirus challenge. Given the efficacy profile in preventive and treatment approaches and the safety record in several immune-competent and immune-compromised animal species, this vaccine platform is ready to be considered for investigational drug licensure. We further propose to consider the rVSV platform for preinvestigational drug use in cases of laboratory exposures with EBOV and MARV. In addition to EBOV and MARV, rVSV-based vaccines are currently being evaluated for a number of other human pathogens, including avian influenza, hepatitis B, HIV, Lassa fever, severe acute respiratory syndrome (SARS), West Nile virus, and Yersinia pestis. Knowledge gained from these studies should advance the development of rVSV-based vaccines for human use.

Funding

This work is supported by the intramural and extramural research programs of the National Institute of Allergy and Infectious Diseases, National Institutes of Health (grant number U01 AI082197 to T. W. G.); and the National Microbiology Laboratory of the Public Health Agency of Canada.

Acknowledgments

Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the University of Texas Medical Branch at Galveston or the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH). The authors thank many colleagues in the field for their contribution to the development and evaluation of the rVSV vaccines for Ebola and Marburg viruses.

References

1. Hevey M, Negley D, Pushko P, Smith J, Schmaljohn A. Marburg virus vaccines based upon alphavirus replicons protect guinea pigs and nonhuman primates. Virology. 1998;251:28–37. [PubMed]

2. Sullivan NJ, Sanchez A, Rollin PE, Yang ZY, Nabel GJ. Development of a preventive vaccine for Ebola virus infection in primates. Nature. 2000;408:605–9. [PubMed]

3. Sullivan NJ, Geisbert TW, Geisbert JB, et al. Accelerated vaccination for Ebola virus haemorrhagic fever in non-human primates. Nature. 2003;424:681–4. [PubMed]

4. Jones SM, Feldmann H, Stroher U, et al. Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses. Nat Med. 2005;11:786–90. [PubMed]

5. Daddario-DiCaprio KM, Geisbert TW, Geisbert JB, et al. Cross-protection against Marburg virus strains using a live, attenuated recombinant vaccine. J Virol. 2006;80:9659–66. [PMC free article] [PubMed]

6. Sullivan NJ, Geisbert TW, Geisbert JB, et al. Immune protection of nonhuman primates against Ebola virus with single low-dose adenovirus vectors encoding modified GPs. PLoS Med. 2006;3:e177. [PMC free article] [PubMed]

7. Bukreyev A, Rollin PE, Tate MK, et al. Successful topical respiratory tract immunization of primates against Ebola virus. J Virol. 2007;81:6379–88. [PMC free article] [PubMed]

8. Warfield KL, Swenson DL, Olinger GG, Kalina WV, Aman MJ, Bavari S. Ebola virus-like particle-based vaccine protects nonhuman primates against lethal Ebola virus challenge. J Infect Dis. 2007;196:S430–7. [PubMed]

9. Geisbert TW, Daddario-DiCaprio KM, Geisbert JB, et al. Vesicular stomatitis virus-based vaccines protect nonhuman primates against aerosol challenge with Ebola and Marburg viruses. Vaccine. 2008;26:6894–900. [PMC free article] [PubMed]

10. Swenson DL, Wang D, Luo M, et al. Vaccine to confer complete protection against multistrain Ebola and Marburg virus infections. Clin Vaccine Immunol. 2008;15:460–7. [PMC free article] [PubMed]

11. Swenson DL, Warfield KL, Larsen T, Alves DA, Coberley SS, Bavari S. Monovalent virus-like particle vaccine protects guinea pigs and nonhuman primates against infection with multiple Marburg viruses. Expert Rev Vaccines. 2008;7:417–29. [PubMed]

12. Geisbert TW, Geisbert JB, Leung A, et al. Single injection vaccine protects nonhuman primates against Marburg virus and three species of Ebola virus. J Virol. 2009;83:7296–304. [PMC free article] [PubMed]

13. Qiu X, Fernando L, Alimonti JB, et al. Mucosal immunization of cynomolgus macaques with the VSVDeltaG/ZEBOV GP vaccine stimulates strong Ebola GP-specific immune responses. PLoS One. 2009;4:e5447. [PMC free article] [PubMed]

14. Geisbert TW, Bailey M, Geisbert JB, et al. Vector choice determines immunogenicity and potency of genetic vaccines against Angola Marburgvirus in nonhuman primates. J Virol. 2010;84:10386–94. [PMC free article] [PubMed]

15. Hensley LE, Mulangu S, Asiedu C, et al. Demonstration of cross-protective vaccine immunity against an emerging pathogenic Ebolavirus species. PLoS Pathog. 2010;6:e1000904. [PMC free article] [PubMed]

16. Pratt WD, Wang D, Nichols DK, et al. Protection of nonhuman primates against two species of Ebola virus infection with a single complex adenovirus vector. Clin Vaccine Immunol. 2010;17:572–81. [PMC free article] [PubMed]

17. Feldmann H, Geisbert TW, Jahrling PB, et al. Filoviridae. In: Fauquet C, Mayo MA, Maniloff J, Desselberger U, Ball LA, editors. Virus taxonomy: Eighth report of the International Committee on Taxonomy of Viruses. San Diego, CA: Elsevier/Academic Press; 2004. pp. 645–53.

18. Sanchez A, Geisbert TW, Feldmann H. Filoviridae: Marburg and Ebola Viruses. In: Knipe DM, Howley PM, editors. Fields virology. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006. pp. 1409–48.

19. Towner JS, Sealy TK, Khristova ML, et al. Newly discovered Ebola virus associated with hemorrhagic fever outbreak in Uganda. PLoS Pathog. 2008;4:e1000212. [PMC free article] [PubMed]

20. Le Guenno B, Formenty P, Wyers M, Gounon P, Walker F, Boesch C. Isolation and partial characterisation of a new strain of Ebola virus. Lancet. 1995;345:1271–4. [PubMed]

21. Rose JK, Schubert M. Rhabdovirus genomes and their products. In: Wagner RR, editor. The Rhabdoviruses. New York, NY: Plenum Publishing Corporation; 1987. pp. 129–66.

22. Brandly CA, Hanson RP. Epizootiology of vesicular stomatitis. Am J Pub Health. 1957;47:205–9. [PubMed]

23. Johnson KM, Vogel JE, Peralta PH. Clinical and serological response to laboratory-acquired human infection by Indiana type vesicular stomatitis virus (VSV) Am J Trop Med Hyg. 1966;15:244–6. [PubMed]

24. Brody JA, Fischer GF, Peralta PH. Vesicular stomatitis virus in Panama. Human serologic patterns in a cattle raising area. Am J Epidemiol. 1967;86:158–61. [PubMed]

25. Roberts A, Buonocore L, Price R, Forman J, Rose JK. Attenuated vesicular stomatitis viruses as vaccine vectors. J Virol. 1999;73:3723–32. [PMC free article] [PubMed]

26. Publicover J, Ramsburg E, Rose JK. Characterization of nonpathogenic, live, viral vaccine vectors inducing potent cellular immune responses. J Virol. 2004;78:9317–24. [PMC free article] [PubMed]

27. Clarke DK, Nasar F, Lee M, et al. Synergistic attenuation of vesicular stomatitis virus by combination of specific G gene truncations and N gene translocations. J Virol. 2007;81:2056–64. [PMC free article] [PubMed]

28. Rose NF, Marx PA, Luckay A, et al. An effective AIDS vaccine based on live attenuated vesicular stomatitis virus recombinants. Cell. 2001;106:539–49. [PubMed]

29. Schnell MJ, Mebatsion T, Conzelmann KK. Infectious rabies virus from cloned cDNA. EMBO J. 1994;13:4195–203. [PubMed]

30. McGettigan JP, Foley HD, Belyakov IM, Berzofsky JA, Pomerantz RJ, Schnell MJ. Rabies virus-based vectors expressing human immunodeficiency virus type 1 (HIV-1) envelope protein induce a strong, cross-reactive cytotoxic T-lymphocyte response against envelope proteins from different HIV-1 isolates. J Virol. 2001;75:4430–4. [PMC free article] [PubMed]

31. McGettigan JP, Sarma S, Orenstein JM, Pomerantz RJ, Schnell MJ. Expression and immunogenicity of human immunodeficiency virus type 1 gag expressed by a replication-competent rhabdovirus-based vaccine vector. J Virol. 2001;75:8724–32. [PMC free article] [PubMed]

32. Siler CA, McGettigan JP, Dietzcshold B, et al. Live and killed rhabdovirus-based vectors as potential hepatitis C vaccines. Virology. 2002;292:24–34. [PubMed]

33. Kretzschmar E, Buonocore L, Schnell MJ, Rose JK. High-efficiency incorporation of functional influenza virus glycoproteins into recombinant vesicular stomatitis viruses. J Virol. 1997;71:5982–9. [PMC free article] [PubMed]

34. Lawson ND, Stillman EA, Whitt MA, Rose JK. Recombinant vesicular stomatitis viruses from DNA. Proc Natl Acad Sci U S A. 1995;92:4477–81. [PubMed]

35. Roberts A, Kretzschmar E, Perkins AS, et al. Vaccination with a recombinant vesicular stomatitis virus expressing an influenza virus hemagglutinin provides complete protection from influenza virus challenge. J Virol. 1998;72:4704–11. [PMC free article] [PubMed]

36. Schnell MJ, Buonocore L, Kretzschmar E, Johnson E, Rose JK. Foreign glycoproteins expressed from recombinant vesicular stomatitis viruses are incorporated efficiently into virus particles. Proc Natl Acad Sci U S A. 1996;93:11359–65. [PubMed]

37. Robain O, Chany-Fournier F, Cerutti I, Màzlo M, Chany C. Role of VSV G antigen in the development of experimental spongiform encephalopathy in mice. Acta Neuropathol. 1986;70:220–6. [PubMed]

38. van den Pol AN, Dalton KP, Rose JK. Relative neurotropism of a recombinant rhabdovirus expressing a green fluorescent envelope glycoprotein. J Virol. 2002;76:1309–27. [PMC free article] [PubMed]

39. Martinez I, Rodriguez LL, Jimenez C, Pauszek SJ, Wertz GW. Vesicular stomatitis virus glycoprotein is a determinant of pathogenesis in swine, a natural host. J Virol. 2003;77:8039–47. [PMC free article] [PubMed]

40. Garbutt M, Liebscher R, Wahl-Jensen V, et al. Properties of replication-competent vesicular stomatitis virus vectors expressing glycoproteins of filoviruses and arenaviruses. J Virol. 2004;78:5458–65. [PMC free article] [PubMed]

41. Jones SM, Stroher U, Fernando L, et al. Assessment of a vesicular stomatitis virus-based vaccine by use of the mouse model of Ebola virus hemorrhagic fever. J Infect Dis. 2007;196:S404–12. [PubMed]

42. Daddario-DiCaprio KM, Geisbert TW, Ströher U, et al. Postexposure protection against Marburg haemorrhagic fever with recombinant vesicular stomatitis virus vectors in non-human primates: An efficacy assessment. Lancet. 2006;367:1399–404. [PubMed]

43. Feldmann H, Jones SM, Daddario-Dicaprio KM, et al. Effective post-exposure treatment of Ebola infection. PLoS Pathog. 2007;3:e2. [PMC free article] [PubMed]

44. Geisbert TW, Daddario-Dicaprio KM, Williams K, et al. Recombinant vesicular stomatitis virus vector mediates post-exposure protection against Sudan Ebola hemorrhagic fever in nonhuman primates. J Virol. 2008;82:5664–8. [PMC free article] [PubMed]

45. Geisbert TW, Hensley LE, Geisbert JB, et al. Postexposure treatment of Marburg virus infection. Emerg Infect Dis. 2010;16:1119–22. [PMC free article] [PubMed]

46. Johnson JE, Nasar F, Coleman JW, et al. Neurovirulence properties of recombinant vesicular stomatitis virus vectors in non-human primates. Virology. 2007;360:36–49. [PMC free article] [PubMed]

47. Geisbert TW, Daddario-Dicaprio KM, Lewis MG, et al. Vesicular stomatitis virus-based Ebola vaccine is well-tolerated and protects immunocompromised nonhuman primates. PLoS Pathog. 2008;4:e1000225. [PMC free article] [PubMed]

48. Tesh RB, Johnson KM. Vesicular stomatitis. In: Hubbert WT, McColloch WF, Schnurrenberger PR, editors. Diseases transmitted from animals to man, 6th ed. Springfield, IL: CC Thomas; 1975. pp. 897–910.

49. Gunther S, Feldmann H, Geisbert TW, et al. Management of an accidental exposure to Ebola virus in the biosafety level 4 laboratory, Hamburg, Germany. J Infect Dis. 2011 in press. [PubMed]

50. Griffin DE, Pan CH, Moss WJ. Measles vaccines. Front Biosci. 2008;13:1352–70. [PubMed]

Articles from The Journal of Infectious Diseases are provided here courtesy of
Oxford University Press