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Vaccine Comparison

Heterologous MARV Protein VLP Irradiated MBGV antigen Marburg virus glycoprotein expressed by baculovirus recombinants Marburg virus-like particles Multivalent DNA vaccine for B. anthracis, Ebola virus, Marburg virus, and VEE virus
Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information
  • Vaccine Ontology ID: VO_0004137
  • Type: Subunit vaccine
  • Antigen: MARV VP40 and GP were used (Swenson et al., 2005).
  • GP gene engineering:
    • Type: Recombinant protein preparation
    • Description: MBGV gene clone pGem-GP was provided by Heinz Feldmann and Anthony Sanchez (Centers for Disease Control and Prevention, Atlanta, GA). The MBGV GP gene from pGem-GP was excised with SalI and subcloned into the SalI site of a shuttle vector. A clone with the MBGV GP gene in the correct orientation was excised with ApaI and NotI, and this fragment was cloned into the ApaI and NotI sites of a VEE replicon plasmid (Hevey et al., 1998).
    • Detailed Gene Information: Click Here.
  • VP40 gene engineering:
    • Type: Recombinant protein preparation
    • Description: An RNA replicon based on VEEV was used as the vector, with the VEE structural genes replaced by VP40. VP40 seems to serve as a matrix protein, affecting interactions between the nucleoprotein complex and lipid membrane. It is also the most abundant part of the virion (Hevey et al., 1998).
    • Detailed Gene Information: Click Here.
  • Adjuvant: Ribi vaccine adjuvant
  • Preparation: Expression plasmids were made through the use of MARV-Musoke strain. To produce the actual viral preparations, MARV-infected cell supernatents were clarified at 1500×g and then pelleted at 9500×g for 4 h in a Sorvall GSA rotor (Swenson et al., 2005).
  • Virulence: GP vaccination formed sufficient protection against homologous filovirus challenge, yet heterologous wild-type VLPs without GP failed to protect. Our data indicate that vaccination with GP was required and sufficient to form an immune response as heterologous wild-type VLPs or hybrid VLPs that did not contain the homologous GP failed. Vaccination with a mixture of EBOV and MARV VLPs was successful in forming an immune response (Swenson et al., 2005).

  • Vaccine Ontology ID: VO_0004128
  • Type: Live, attenuated vaccine
  • Antigen: The full-length and truncated GP were expressed by baculovirus recombinants (Hevey et al., 1997). Both antigens were abundantly glycosylated with both N- and O-linked glycans.
  • NP from Marburg virus Musoke gene engineering:
    • Type: Recombinant protein preparation
    • Description: This Musoke NP gene was amplified by PCR, and subcloned to create MARV adenovirus vaccine targeted against the Musoke strain of MARV (Wang et al., 2006).
    • Detailed Gene Information: Click Here.
  • GP gene engineering:
    • Type: Recombinant protein preparation
    • Description: This Musoke GP gene was amplified by PCR, and subcloned to create MARV adenovirus vaccine targeted against the Musoke strain of MARV (Wang et al., 2006).
    • Detailed Gene Information: Click Here.
  • Preparation: MBGV glycoprotein (GP) was expressed in Baculovirus recombinants either as a slightly truncated product secreted into medium or a complete, cell-associated molecule(Hevey et al., 1997).
  • Virulence: Irradiated MBGV antigen was protective against two MBGV strains (Musoke and Ravn). The recombinant truncated glycoprotein did elicit protection against challenge with the MBGV isolate from which it was taken(Hevey et al., 1997).
  • Vaccine Ontology ID: VO_0004117
  • Type: Subunit vaccine
  • Antigen: MARV or EBOV VP40 and GP (Warfield et al., 2004).
  • GP gene engineering:
    • Type: Recombinant protein preparation
    • Description: This Musoke GP gene was amplified by PCR, and subcloned to create MARV adenovirus vaccine targeted against the Musoke strain of MARV (Wang et al., 2006).
    • Detailed Gene Information: Click Here.
  • VP40 gene engineering:
    • Type: Recombinant protein preparation
    • Description: An RNA replicon based on VEEV was used as the vector, with the VEE structural genes replaced by VP40. VP40 seems to serve as a matrix protein, affecting interactions between the nucleoprotein complex and lipid membrane. It is also the most abundant part of the virion (Hevey et al., 1998).

    • Detailed Gene Information: Click Here.
  • Adjuvant: Ribi vaccine adjuvant
  • Preparation: To generate mVLPs, 293T cells were co-transfected with pWRG 7077 vectors encoding for MARV VP40 and GP using Lipofectamine 2000 (Invitrogen, Carlsbad, CA). To purify the VLPs, the cell supernatants were cleared from cellular debris and subsequently pelleted at 9500×g for 4 h. The crude VLP preparations were then separated on a 20â��60% continuous sucrose gradient centrifuged. The VLPs were concentrated by a second centrifugation and resuspended in endotoxin-free phosphate-buffered saline (PBS) (Warfield et al., 2004).
  • Virulence: Guinea pigs that were vaccinated with inactivated MARV or mVLPs developed MARV-specific antibody titers(Warfield et al., 2004).
  • Vaccine Ontology ID: VO_0004130
  • Type: DNA vaccine
  • Antigen: Multiple antigens from B. anthracis, Ebola virus, Marburg virus, and VEE virus were used. Specifically, this DNA vaccine includes Protective Antigen (PA) from B. anthracis, Glycoprotein (GP) and Nucleoprotein (NP) from Ebloa virus, Glycoprotein (GP) from Marburg virus strain Ravn, and 26S from VEE virus (Riemenschneider et al., 2003).
  • PagA from Bacillus anthracis gene engineering:
    • Type: Recombinant protein preparation
    • Description: A DNA vaccine for the anthrax was made by PCR-amplifying the PA gene (Riemenschneider et al., 2003).
    • Detailed Gene Information: Click Here.
  • NP from Zaire ebolavirus gene engineering:
    • Type: Recombinant protein preparation
    • Description: Ebola NP genes were cloned and the vaccine was produced without additional signal sequence with the use of plasmid pWRG7077 (Riemenschneider et al., 2003).
    • Detailed Gene Information: Click Here.
  • GP gene engineering:
    • Type: Recombinant protein preparation
    • Description: Ebola NP genes were cloned and the vaccine was produced without additional signal sequence with the use of plasmid pWRG7077 (Riemenschneider et al., 2003).
    • Detailed Gene Information: Click Here.
  • GP from Marburg virus Ravn gene engineering:
    • Type: Recombinant protein preparation
    • Description: This Ravn GP gene was amplified by PCR, and subcloned to create MARV adenovirus vaccine targeted against the Ci67strain of MARV (Wang et al., 2006).
    • Detailed Gene Information: Click Here.
  • 26S mRNA from VEEV gene engineering:
    • Type: Recombinant protein preparation
    • Description: The vaccine for 26S mRNA was produced without additional signal sequence with the use of plasmid pWRG7077 (Riemenschneider et al., 2003).
    • Detailed Gene Information: Click Here.
  • Vector: pWRG7079 (Riemenschneider et al., 2003)
  • Preparation: The necessary genes were inserted into expression plasmids following a cytomegalovirus immediate early promotor. MARV was procured through experiementally infected monkeys, then passed three times (Ravn) or one time(Musoke) in Vero cells. Inbred Strain 13 and outbred Hartley guinea pigs were injected subcutaneously with the vaccine. Responses were measured by IgG antibody ELISA with the use of cobalt-irradiated purified MARV in both strains. A study also included non-human primates, which underwent serum tests for viremia determination and blood chemistry(Riemenschneider et al., 2003).
Host Response Host Response Host Response Host Response Host Response

Guinea pig Response

  • Host Strain: Strain 13
  • Vaccination Protocol: Strain 13 guinea pigs were vaccinated once with mVLPs, eVLPs, or an equal mixture of eVLPs and mVLPs in RIBI adjuvant, and the serum antibody levels against MARV and EBOV were measured (via ELISA) prior to challenge (Swenson et al., 2005).
    Control guinea pigs were vaccinated with RIBI adjuvant alone. Serum samples from the guinea pigs were
    obtained immediately before (PRE) or 28 days post-challenge (POST).Guinea pigs were vaccinated
  • Persistence: Not noted.
  • Immune Response: Animals vaccinated with the wild-type eVLP or e/m-VLPs did not have high serum antibody titers against MARV, but did have them against EBOV. Injection with mVLP and m/e-VLP vaccination resulted in high titers against MARV but not against EBOV. The vaccination containing EBOV GPin the form of eVLPor e/m-VLP resulted in antibodies against EBOV but not MARV. Finally, animals vaccinated with mVLP orm/e-VLP did not develop significant antibody titers against EBOV or MARV (Swenson et al., 2005).
  • Side Effects: None noted.
  • Challenge Protocol: Guinea pigs were challenged 28 days after a single vaccination with 1000 pfu of guinea pig-adapted MARV or EBOV (Swenson et al., 2005).
  • Efficacy: Guinea pigs challenged wuth VLPs containing homologous GP were protected from a lethal filovirus, and a eVLP or e/m-VLP vaccination yielded protection against EBOV infection. Vaccines containing heterologous proteins or homologous VP40 did not protect against lethal challenge (Swenson et al., 2005).

Guinea pig Response

  • Host Strain: Strain 13
  • Vaccination Protocol: Animals were immunized with irradiated MBGV (strains Musoke and Ravn)(Hevey et al., 1997).
  • Persistence: None noted.
  • Immune Response: Not noted for irradiated MBGV specifically.
  • Side Effects: None noted.
  • Challenge Protocol: All animals challenged with strains Musoke and Ravn survived without regard to challenge virus (Hevey et al., 1997).
  • Efficacy: Gradient-purified, irradiated virus was able to completely protect strain 13 guinea pigs from challenge with either MBGV (strain Musoke) or
    indicated that the product immunoprecipitated from GP- MBGV (strain Ravn)(Hevey et al., 1997).

Guinea pig Response

  • Host Strain: Strain 13 and Hartley
  • Vaccination Protocol: Groups of animals were challenged with Ravn and Musoke strains, and ELISA titers were use to measure response 28 days after challenge (Hevey et al., 1997).
  • Immune Response: Irradiated, gradient-purified virus completely protected Strain 13 from both Ravn and Musoke MBGV strains (Hevey et al., 1997).
  • Challenge Protocol: Guinea pigs (Hartley and Strain 13) were divided into groups and injected with irradiated GP or recombinant GP. ELISA titers measureing response were taken 2 days before challenge and 28 days after for comparison (Hevey et al., 1997).
  • Description: Animals that recieved the MBGV antigen (strainRavn) had a lower survival rate than those challenged with the Musoke strain(Hevey et al., 1997).

Guinea pig Response

  • Host Strain: Strain 13
  • Vaccination Protocol: Guinea pigs were vaccinated intramuscularly with 50 μg of mVLPs, eVLPs, or iMARV with 200 μl of RIBI monophosphoryl lipid+synthetic trehalose dicorynomycolate+cell wall skeleton emulsion diluted in endotoxin-free PBS (Warfield et al., 2004).
  • Persistence: None noted.
  • Immune Response: Both inactivated MARV and mVLP induced maximal humoral responses to MARV after only two vaccinations (Warfield et al., 2004) .
  • Side Effects: Not noted.
  • Challenge Protocol: Thirty days after the third vaccination, the guinea pigs were challenged subcutaneously with 1000 plaque-forming units (pfu) or 2000 LD50 of guinea pig-adapted MARV diluted in PBS [18](Warfield et al., 2004).
  • Efficacy: Strong filovirus-specific antibody responses correlate with vaccine protective efficacy in guinea pigs(Warfield et al., 2004).

Guinea pig Response

  • Host Strain: Strain 13 and Hartley
  • Vaccination Protocol: Gun-vaccinated guinea pigs were gene gun-vaccinated three (Musoke) or four (Ravn) times at 4-week intervals with approximately 2.5 μg of the MARV GP DNA (Riemenschneider et al., 2003).
  • Persistence: Not noted.
  • Immune Response: All of the MARV GP DNA-vaccinated guinea pigs developed antibodies to MARV(Riemenschneider et al., 2003).
  • Side Effects: Not noted.
  • Challenge Protocol: The challenge was a subcutaneous injection of 1000 plaque forming units (pfu) of homologous virus 4 weeks after the final vaccination for each guinea pig (Riemenschneider et al., 2003).
  • Efficacy: Guinea pigs vaccinated with control DNA were viremic at day 7 post-challenge, as measured by plaque assay, and were infected by day 9. All guinea pigs vaccinated with the GP DNA vaccines were aviremic at day 7 and appreared healthy throughout the observation period(Riemenschneider et al., 2003).
References References References References References
Hevey et al., 1998: 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 Nov 10; 251(1); 28-37. [PubMed: 9813200 ].
Swenson et al., 2005: Swenson DL, Warfield KL, Negley DL, Schmaljohn A, Aman MJ, Bavari S. Virus-like particles exhibit potential as a pan-filovirus vaccine for both Ebola and Marburg viral infections. Vaccine. 2005; 23(23); 3033-3042. [PubMed: 15811650].
Hevey et al., 1997: Hevey M, Negley D, Geisbert J, Jahrling P, Schmaljohn A. Antigenicity and vaccine potential of Marburg virus glycoprotein expressed by baculovirus recombinants. Virology. 1997 Dec 8; 239(1); 206-16. [PubMed: 9426460 ].
Hevey et al., 1997: Hevey M, Negley D, Geisbert J, Jahrling P, Schmaljohn A. Antigenicity and vaccine potential of Marburg virus glycoprotein expressed by baculovirus recombinants. Virology. 1997 Dec 8; 239(1); 206-16. [PubMed: 9426460 ].
Wang et al., 2006: Wang D, Schmaljohn AL, Raja NU, Trubey CM, Juompan LY, Luo M, Deitz SB, Yu H, Woraratanadharm J, Holman DH, Moore KM, Swain BM, Pratt WD, Dong JY. De novo syntheses of Marburg virus antigens from adenovirus vectors induce potent humoral and cellular immune responses. Vaccine. 2006 Apr 5; 24(15); 2975-86. [PubMed: 16530297 ].
Hevey et al., 1998: 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 Nov 10; 251(1); 28-37. [PubMed: 9813200 ].
Wang et al., 2006: Wang D, Schmaljohn AL, Raja NU, Trubey CM, Juompan LY, Luo M, Deitz SB, Yu H, Woraratanadharm J, Holman DH, Moore KM, Swain BM, Pratt WD, Dong JY. De novo syntheses of Marburg virus antigens from adenovirus vectors induce potent humoral and cellular immune responses. Vaccine. 2006 Apr 5; 24(15); 2975-86. [PubMed: 16530297 ].
Warfield et al., 2004: Warfield KL, Swenson DL, Negley DL, Schmaljohn AL, Aman MJ, Bavari S. Marburg virus-like particles protect guinea pigs from lethal Marburg virus infection. Vaccine. 2004 Sep 3; 22(25-26); 3495-502. [PubMed: 15308377 ].
Riemenschneider et al., 2003: Riemenschneider J, Garrison A, Geisbert J, Jahrling P, Hevey M, Negley D, Schmaljohn A, Lee J, Hart MK, Vanderzanden L, Custer D, Bray M, Ruff A, Ivins B, Bassett A, Rossi C, Schmaljohn C. Comparison of individual and combination DNA vaccines for B. anthracis, Ebola virus, Marburg virus and Venezuelan equine encephalitis virus. Vaccine. 2003; 21(25-26); 4071-4080. [PubMed: 12922144 ].
Wang et al., 2006: Wang D, Schmaljohn AL, Raja NU, Trubey CM, Juompan LY, Luo M, Deitz SB, Yu H, Woraratanadharm J, Holman DH, Moore KM, Swain BM, Pratt WD, Dong JY. De novo syntheses of Marburg virus antigens from adenovirus vectors induce potent humoral and cellular immune responses. Vaccine. 2006 Apr 5; 24(15); 2975-86. [PubMed: 16530297 ].