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Vaccine Detail

AAVLP(HPV16/31L2)
Vaccine Information
  • Vaccine Name: AAVLP(HPV16/31L2)
  • Target Pathogen: Human Papillomavirus
  • Target Disease: HPV infection
  • Type: Recombinant vector vaccine
  • Status: Clinical trial
  • Host Species for Licensed Use: None
  • Host Species as Laboratory Animal Model: Rabbits and Rats
  • Antigen: Adeno-associated virus serotype 2 (AAV2) capsids
  • L2 HPV 16 gene engineering:
    • Type: Recombinant protein preparation
    • Description: L2 proteins harbors several regions that can be targeted by neutraliizing antibodies (Nieto et al., 2012).
    • Detailed Gene Information: Click Here.
  • L2 HPV31 gene engineering:
    • Type: Recombinant protein preparation
    • Description: Insertion of L2 HPV31 into VP3 at positions 583 and 453.
    • Detailed Gene Information: Click Here.
  • Preparation: Generated AAVLPs displaying HPV16 L2 epitopes in position 587 and HPV31 L2 epitopes in position 453. (Nieto et al., 2012).
  • Immunization Route: Intramuscular injection (i.m.)
  • Description: Insertion of a neutralizing epitope (amino acids 17–36) from L2 of HPV16 and HPV31 into VP3 at positions 587 and 453, respectively, permitted assembly into empty AAV particles (AAVLP(HPV16/31L2)) (Nieto et al., 2012).
Host Response

Mouse Response

  • Host Strain: Balb/c and C57BL/6
  • Vaccination Protocol: Immunized C57BL/6 mice either with a low dose (LD) (1E+11 particles equivalent to 0.6 µg of protein) or high dose (HD) (5E+12 particles equivalent to 30 µg) with or without adjuvant (+M) (montanide ISA 51). (Nieto et al., 2012).
  • Persistence: Mice immunized with LD+M or HD+M developed 25 and 50 fold higher HPV16 L2-specific antibodies titers, respectively, than mice immunized with a LD of particles without adjuvant. There was little difference between the mice immunized with LD+M and mice immunized with HD+M. Sera of all mice vaccinated with TrXL2+M had HPV16 L2-specific antibodies. (Nieto et al., 2012).

Rabbit Response

  • Vaccination Protocol: Three ZIKA hybrid rabbits were immunized four times with AAVLP(HPV16/31L2) particles (2E+12 capsids equivalent to 13.2 µg) adjuvanted with montanide ISA720. Rabbit sera were administered intraperitoneally to naïve mice. Rabbit sera against AAVLP with an epitope of the cholesteryl ester transfer protein (AAVLP TP18) were used to detect the unspecific effect of AAVLP induced antibodies. Vaginal infection of mice is detected three days after challenge as luminescence signal after injection of the challenged mice with luciferin. (Nieto et al., 2012)
  • Persistence: The passive transfer of AAVLP(HPV16/31L2) sera protected mice from vaginal challenge with HPV16 PsV, whereas the AAVLP TP18 control serum failed to protect the mice. (Nieto et al., 2012)
References
Nieto et al., 2012: Nieto K, Weghofer M, Sehr P, Ritter M, Sedlmeier S, Karanam B, Seitz H, Müller M, Kellner M, Hörer M, Michaelis U, Roden RB, Gissmann L, Kleinschmidt JA. Development of AAVLP(HPV16/31L2) particles as broadly protective HPV vaccine candidate. PloS one. 2012; 7(6); e39741. [PubMed: 22761884].