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Vaccine Detail

Rotavirus VP6 Protein Vaccine
Vaccine Information
  • Vaccine Name: Rotavirus VP6 Protein Vaccine
  • Target Pathogen: Rotavirus
  • Target Disease: Gastroenteritis
  • Vaccine Ontology ID: VO_0004043
  • Type: Subunit vaccine
  • Status: Research
  • VP6 gene engineering:
    • Type: Recombinant protein preparation
    • Description:
    • Detailed Gene Information: Click Here.
  • Adjuvant: LTR192G
    • Adjuvant name: LTR192G
    • VO adjuvant 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
    • Adjuvant name: Cholera toxin A1-subunit-ProteinA D-fragment fusion protein
    • VO adjuvant 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

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
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].