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Vaccine Comparison

HSVT[VP7/6/2] Rotavirus Chimeric VP6 protein Vaccine Rotavirus VP2/VP 6 Protein Vaccine Rotavirus VP4/VP7 Protein Vaccine Rotavirus VP6 Protein Vaccine
Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information
  • Vaccine Ontology ID: VO_0004687
  • Type: Recombinant vector vaccine
  • Status: Research
  • Host Species for Licensed Use: Baboon
  • VP2 gene engineering:
    • Type: Recombinant vector construction
    • Description: HSV-1 amplicon vectors encoding individual or multiple structural RV proteins from a polycistronic transgene cassette in mammalian cells (Laimbacher et al., 2012).
    • Detailed Gene Information: Click Here.
  • VP6 gene engineering:
    • Type: Recombinant vector construction
    • Description: HSV-1 amplicon vectors encoding individual or multiple structural RV proteins from a polycistronic transgene cassette in mammalian cells (Laimbacher et al., 2012).
    • Detailed Gene Information: Click Here.
  • VP7 gene engineering:
    • Type: Recombinant vector construction
    • Description: HSV-1 amplicon vectors encoding individual or multiple structural RV proteins from a polycistronic transgene cassette in mammalian cells (Laimbacher et al., 2012).
    • Detailed Gene Information: Click Here.
  • Preparation: Herpes simplex virus type 1 (HSV-1) amplicon vectors were constructed to coexpress the rotavirus (RV) structural genes VP2, VP6, and VP7 (Laimbacher et al., 2012).
  • Immunization Route: Intramuscular injection (i.m.)
  • Vaccine Ontology ID: VO_0004224
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: Chimeric VP6 protein (Choi et al., 2002).
  • Adjuvant: Adjumer
  • Immunization Route: intranasal immunization
  • Vaccine Ontology ID: VO_0004160
  • Type: Subunit vaccine
  • Status: Research
  • VP2 gene engineering:
    • Type: Recombinant protein preparation
    • Detailed Gene Information: Click Here.
  • Adjuvant: cholera toxin
    • VO ID: VO_0000143
    • Description: A detoxified version of cholera toxin, CT-E29H (Siadat-Pajouh and Cai, 2001).
  • Immunization Route: Orally
  • Vaccine Ontology ID: VO_0004161
  • Type: Subunit vaccine
  • Status: Research
  • VP4 gene engineering:
    • Type: Recombinant vector construction
    • Detailed Gene Information: Click Here.
  • VP7 gene engineering:
    • Type: Recombinant vector construction
    • Detailed Gene Information: Click Here.
  • VP6 gene engineering:
    • Type: Recombinant vector construction
    • Detailed Gene Information: Click Here.
  • Adjuvant: incomplete Freunds adjuvant
  • Immunization Route: Intramuscular injection (i.m.)
  • Vaccine Ontology ID: VO_0004043
  • Type: Subunit vaccine
  • Status: Research
  • VP6 gene engineering:
    • Type: Recombinant protein preparation
    • Detailed Gene Information: Click Here.
  • Adjuvant: LTR192G
    • VO ID: VO_0001321
    • Description: Two adjuvants were used in this study and were either mixed with MBP::VP6 prior to immunization or were administered separately. One was the attenuated E. coli heat-labile toxin LT(R192G). LT(R192G) carries a mutation in the trypsin cleavage site of the A subunit at arginine 192 (replaced by glycine) which abrogates cleavage and attenuates the toxicity of the protein. The other adjuvant was CTA1-DD which is composed of the enzymatically active A1 subunit of cholera toxin combined with a dimer of an immunoglobulin binding element from S. aureus protein A. Pre-clinical evaluations of CTA1-DD have reported it to be nontoxic (McNeal et al., 2007).
  • Adjuvant: Cholera toxin A1-subunit-ProteinA D-fragment fusion protein
    • VO ID: VO_0001290
    • Description: Two adjuvants were used in this study and were either mixed with MBP::VP6 prior to immunization or were administered separately. One was the attenuated E. coli heat-labile toxin LT(R192G). LT(R192G) carries a mutation in the trypsin cleavage site of the A subunit at arginine 192 (replaced by glycine) which abrogates cleavage and attenuates the toxicity of the protein. The other adjuvant was CTA1-DD which is composed of the enzymatically active A1 subunit of cholera toxin combined with a dimer of an immunoglobulin binding element from S. aureus protein A. Pre-clinical evaluations of CTA1-DD have reported it to be nontoxic (McNeal et al., 2007).
  • Immunization Route: Intraperitoneal injection (i.p.)
Host Response Host Response Host Response Host Response Host Response

Mouse Response

  • Vaccination Protocol: intramuscular injection of mice with the amplicon vectors as a two-dose regimen without adjuvants (Laimbacher et al., 2012).
  • Vaccine Immune Response Type: VO_0001030
  • Challenge Protocol: Immunized mice were challenged with live wild-type (wt) rotavirus infection (Laimbacher et al., 2012).
  • Efficacy: Immunized mice were partially protected at the mucosal level (Laimbacher et al., 2012).

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were lightly anaesthetized in a closed vessel with Metafane (methoxyflurane, Pitman–Moore Inc., Mundelein, IL). Vaccine formulations containing chimeric VP6 admixed with different adjuvants were then delivered intranasally or orally into groups of mice. Two i.n. doses (60 μl per dose, 30 μl per nostril) or two oral doses (100 μl per dose), separated by 2 weeks, were delivered. Each dose of immunogen consisted of 9 μg of purified chimeric VP6, which was mixed with LT(R192G) (10 μg), CTA1-DD (10 μg), Adjumer® (50 μg), CpG ODN (10 μg) or QS-21 (20 μg) just before immunization. The amounts of adjuvants used were based on the amounts determined for other immunogens. A group of unimmunized mice served as the control in each experiment (Choi et al., 2002).
  • Immune Response: Mice immunized with Adjumer®, CTA1-DD or LT(R192G), also developed low titers of fecal rotavirus IgA. Use of Adjumer as an adjuvant had a large IgG1 titer but no increase in IgG2a titer (Choi et al., 2002).
  • Challenge Protocol: Four weeks after the last immunization, mice were orally (gavage) challenged with 4×104 FFUs (100 μl, 100 SD50) of passage-9 EDIM rotavirus (Choi et al., 2002).
  • Efficacy: Mice immunized with chimeric VP6 and Adjumer had a 35% reduction in shedding of virus compared to unimmunized mice (Choi et al., 2002).

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: Four-week-old BALB/c mice were vaccinated twice at Weeks 0 and 2 either orally or i.n. with 100 and 10 ug of 2/6-VLPs, respectively; each vaccine dose was formulated with 10 mg of CT-E29H. A third group of BALB/c mice (n = 4) received 2/6-VLPs with CT-E29H i.n. followed by an oral booster immunization (i.e., mixed group). Control mice in this experiment were inoculated with CT-E29H, 13 TNC, and 2/6-VLPs alone. Each mouse was inoculated i.n. with 20 uL of inoculums , 2 uL at a time into alternating nares at 1-min intervals (Siadat-Pajouh and Cai, 2001).
  • Challenge Protocol: All animals were challenged by gavage with 10 SD50 of wild-type EDIM rotavirus at week 13 (BALB/c mice). The trypsin-activated challenge virus (100 uL) was administered following oral inoculation of 100 uL of 4% sodium bicarbonate solution to neutralize gastric acidity (Siadat-Pajouh and Cai, 2001).
  • Efficacy: In BALB/c mice, intranasal vaccination with 2/6-VLPs and CT-E29H proved protective (PRAS 5 98.7%), in contrast to intranasal immunization with 2/6-VLPs alone (PRAS 5 39%), demonstrating the significant augmentation in protective immune responses due to CT-E29H. BALB/c mice in all three immunization groups showed nearly complete protection from the challenge. PRAS was 99.6, 98.8, and 98.8% for the oral, intranasal, and the mixed groups, respectively. The unimmunized control group shed significantly more viral antigen than the three immunized groups (Siadat-Pajouh and Cai, 2001).

Mouse Response

  • Host Strain: CD-1
  • Vaccination Protocol: For primary immunization, each immunogen (based on 10μg of VP6) was emulsified with an equal volume of Freund's complete adjuvant. For the secondary 'booster' immunizations, each immunogen was emulsified with an equal volume of Freund's incomplete adjuvant. Eight groups of mice (Strain CD-1 ; ten animals/group) were immunized intramuscularly with the immunogen preparations. The primary immunization was given to the mice at 7 weeks of age and was followed by two booster immunizations at 2 week intervals. The mice were bred and litters were born to the dams at 12 to 14 weeks of age (Redmond et al., 1993).
  • Challenge Protocol: Pups were allowed to suckle their dams and ten pups/group were challenged at 7 days of age with one of four rotavirus isolates. The challenge dose for each isolate was ~ 106 p.f.u./mouse, suspended in MEM in 100 microliter volume. This dose had been demonstrated to produce diarrhoea in 100% of neonatal mice born to rotavirus antibody-free dams 26. The virus challenge preparations were administered by intubation of the stomach with a soft flexible plastic feeding tube. The appearance of diarrhoea was scored clinically for up to 72 h postchallenge (Redmond et al., 1993).
  • Efficacy: The highest antibody and virus neutralization titres were achieved following vaccination with VP4 cell-lysate. The significance of VP4 in the neutralization of virus was clearly defined by the high virus neutralization titres achieved following vaccination with any preparation containing VP4 (Redmond et al., 1993).

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: Under sedation, mice were immunized intrarectally by gently inserting a micropipette tip ca. 0.5 cm and instilling a 10 μl volume. The total volume for all immunogens used was 20 μl split in two doses of 10 μl. Groups of mice received two intrarectal immunizations of 3 μg MBP::VP6 and either LT(R192G) or CTA1-DD (10 μg of either adjuvant). This quantity of MBP::VP6 was used, based on the concentration of the MBP::VP6, to keep the volume under 20 μl to avoid loss from the anus. Groups of control mice were either mock immunized with phosphate-buffered saline (PBS) only or with MBP::VP6, LT(R192G), or CTA1-DD only. Immunizations were separated by 2 weeks (McNeal et al., 2007).
  • Challenge Protocol: Four weeks after the second immunization, animals were either challenged with 105 shedding dose-50 (SD50) of wt EDIM by oral gavage to measure protection against fecal rotavirus shedding or they were sacrificed and their spleen cells were isolated and used for in vitro stimulation studies (McNeal et al., 2007).
  • Efficacy: Intranasal or oral delivery of the chimeric rotavirus VP6 protein MBP::VP6 to mice elicited >90% reductions in fecal rotavirus shedding after murine rotavirus challenge (McNeal et al., 2007).
  • Host Ifng (Interferon gamma) response
    • Description: Splenic lymphocytes obtained 42 days after first immunization were stimulated for 18 hours with MBP::VP6. LT(R192G)+MBP:VP6 and CTA1-DD+MBP:VP6 produced significantly more IFN-gamma than did mock immunized (PBS-vaccinated) mice (McNeal et al., 2007).
    • Detailed Gene Information: Click Here.
  • Host IL-17 response
    • Description: Splenic lymphocytes obtained 42 days after first immunization were stimulated for 18 hours with MBP::VP6. LT(R192G)+MBP:VP6 produced significantly more IL-17 than did mock immunized (PBS-vaccinated) mice (McNeal et al., 2007).
    • Detailed Gene Information: Click Here.
References References References References References
Laimbacher et al., 2012: Laimbacher AS, Esteban LE, Castello AA, Abdusetir Cerfoglio JC, Argüelles MH, Glikmann G, D'Antuono A, Mattion N, Berois M, Arbiza J, Hilbe M, Schraner EM, Seyffert M, Dresch C, Epstein AL, Ackermann M, Fraefel C. HSV-1 amplicon vectors launch the production of heterologous rotavirus-like particles and induce rotavirus-specific immune responses in mice. Molecular therapy : the journal of the American Society of Gene Therapy. 2012; 20(9); 1810-1820. [PubMed: 22713696].
Choi et al., 2002: Choi AH, McNeal MM, Flint JA, Basu M, Lycke NY, Clements JD, Bean JA, Davis HL, McCluskie MJ, VanCott JL, Ward RL. The level of protection against rotavirus shedding in mice following immunization with a chimeric VP6 protein is dependent on the route and the coadministered adjuvant. Vaccine. 2002; 20(13-14); 1733-1740. [PubMed: 11906760].
Siadat-Pajouh and Cai, 2001: Siadat-Pajouh M, Cai L. Protective efficacy of rotavirus 2/6-virus-like particles combined with CT-E29H, a detoxified cholera toxin adjuvant. Viral immunology. 2001; 14(1); 31-47. [PubMed: 11270595].
Redmond et al., 1993: Redmond MJ, Ijaz MK, Parker MD, Sabara MI, Dent D, Gibbons E, Babiuk LA. Assembly of recombinant rotavirus proteins into virus-like particles and assessment of vaccine potential. Vaccine. 1993; 11(2); 273-281. [PubMed: 8382422].
McNeal et al., 2007: McNeal MM, Basu M, Bean JA, Clements JD, Lycke NY, Ramne A, Löwenadler B, Choi AH, Ward RL. Intrarectal immunization of mice with VP6 and either LT(R192G) or CTA1-DD as adjuvant protects against fecal rotavirus shedding after EDIM challenge. Vaccine. 2007; 25(33); 6224-6231. [PubMed: 17629371].