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Vaccine Comparison

Human papillomavirus DNA vaccine CRT/E7 DNA Human papillomavirus DNA vaccine E7IR Human papillomavirus DNA vaccine E7SH DNA Human papillomavirus DNA vaccine hCRTE6E7L2 DNA encoding CRT linked to E6, E7 and L2 Human papillomavirus DNA vaccine pC16-L1 encoding L1 Human papillomavirus DNA vaccine Pe7(pcDNA3-Sig/sE7/LAMP) encoding E7 Human papillomavirus DNA vaccine pNGVL4a-E6/opt Human papillomavirus E7 protein vaccine Human papillomavirus L2 protein vaccine LM1-2-E7
Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information
  • Vaccine Ontology ID: VO_0004331
  • Type: DNA vaccine
  • Status: Research
  • Host Species as Laboratory Animal Model: Mouse
  • E7 gene engineering:
    • Type: DNA vaccine construction
    • Description: Vector pCDNA3 expressed E7 protein of HPV 16 and 18 (Cheng et al., 2001).
    • Detailed Gene Information: Click Here.
  • Vector: pCDNA3 (Cheng et al., 2001)
  • Immunization Route: Intramuscular injection (i.m.)
  • Vaccine Ontology ID: VO_0004332
  • Type: DNA vaccine
  • Status: Research
  • Host Species as Laboratory Animal Model: Mouse
  • E7 gene engineering:
    • Type: DNA vaccine construction
    • Description: Vector APL023expressed the E7 gene (Brinkman et al., 2007).
    • Detailed Gene Information: Click Here.
  • Vector: APL023 (Brinkman et al., 2007)
  • Immunization Route: Gene gun
  • Vaccine Ontology ID: VO_0004333
  • Type: DNA vaccine
  • Status: Research
  • Host Species as Laboratory Animal Model: Mouse
  • E7 gene engineering:
    • Type: DNA vaccine construction
    • Description: Vector pCDNA3 expressed the E7 oncogene of the human papillomavirus type 16 (HPV 16) (Osen et al., 2001).
    • Detailed Gene Information: Click Here.
  • Vector: pCDNA3 (Osen et al., 2001)
  • Immunization Route: Intramuscular injection (i.m.)
  • Vaccine Ontology ID: VO_0004475
  • Type: DNA vaccine
  • Status: Research
  • Host Species as Laboratory Animal Model: Mouse
  • E6 gene engineering:
    • Type: DNA vaccine construction
    • Description: Vector pNGVL4a vector (National Gene Vector lab) expressed human calreticulin (CRT) linked to HPV16 early proteins, E6 and E7 and the late protein L2 (hCRTE6E7L2) (Kim et al., 2008).
    • Detailed Gene Information: Click Here.
  • E7 gene engineering:
    • Type: DNA vaccine construction
    • Description: Vector pNGVL4a vector (National Gene Vector lab) expressed human calreticulin (CRT) linked to HPV16 early proteins, E6 and E7 and the late protein L2 (hCRTE6E7L2) (Kim et al., 2008).
    • Detailed Gene Information: Click Here.
  • L2 gene engineering:
    • Type: Recombinant protein preparation
    • Description: Vector pNGVL4a vector (National Gene Vector lab) expressed human calreticulin (CRT) linked to HPV16 early proteins, E6 and E7 and the late protein L2 (hCRTE6E7L2) (Kim et al., 2008).
    • Detailed Gene Information: Click Here.
  • CRTC gene engineering:
    • Type: DNA vaccine construction
    • Description: Vector pNGVL4a vector (National Gene Vector lab) expressed human calreticulin (CRT) linked to HPV16 early proteins, E6 and E7 and the late protein L2 (hCRTE6E7L2) (Kim et al., 2008).
    • Detailed Gene Information: Click Here.
  • Vector: pNGVL4a vector (National Gene Vector lab) (Kim et al., 2008)
  • Immunization Route: Gene gun
  • Vaccine Ontology ID: VO_0004329
  • Type: DNA vaccine
  • Status: Research
  • Host Species as Laboratory Animal Model: Mouse
  • E7 gene engineering:
    • Type: DNA vaccine construction
    • Description: Vector pcDNA3 expressed HPV oncogenic proteins E7 (Sin, 2009).
    • Detailed Gene Information: Click Here.
  • Vector: pcDNA3 (Sin, 2009)
  • Immunization Route: Intramuscular injection (i.m.)
  • Vaccine Ontology ID: VO_0011480
  • Type: DNA vaccine
  • Status: Research
  • Antigen: Human papillomavirus E6
  • E6 gene engineering:
    • Type: DNA vaccine construction
    • Description: To generate pNGVL4a-E6, E6 was isolated from pcDNA3-E6 and cloned into pNGVL4a vector. To generate pNGVL4a-E6/opt, codonoptimized E6 synthesized by GenScript Corporation (Piscataway, NJ) was cloned into EcoRI/BamHI of pNGVL4a vector. The DNA and amino acid sequences of the wild-type E6 gene as well as the codon-optimized E6 were fully sequenced (Lin et al., 2006).
    • Detailed Gene Information: Click Here.
  • Vector: pNGVL4a
  • Immunization Route: Intradermal injection (i.d.)
  • Vaccine Ontology ID: VO_0011395
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: Human papillomavirus E7
  • E7 gene engineering:
    • Type: Recombinant protein preparation
    • Description: An 87-bp DNA fragment coding for the HPV16 E7 peptide38–61 was amplified by PCR from pHPV-16. The E738–61 24-residue peptide, named E7p, and the E749–57 CTL epitope were synthesized in Bioasia Corporation (Shanghai, China). E. coli BL21 (DE3) pLysS cells, transformed with E7p/mcIgG-pET21a, were cultured overnight in 6 ml ZB medium. A 300 ml of LB medium was inoculated with the 6 ml ZB bacteria culture. After a 2-h rotation at 30°C and 200 rpm, chimeric protein expression was induced by the addition of IPTG (isopropyl-β-D-thiogalactopyranoside) to a concentration of 1.0 mM. After a 9-h induction period, the cells were harvested by centrifugation at 5000 rpm for 5 min at 4°C (Qin et al., 2005).
    • Detailed Gene Information: Click Here.
  • Adjuvant: incomplete Freunds adjuvant
  • Immunization Route: Subcutaneous injection
  • Vaccine Ontology ID: VO_0011397
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: Human papillomavirus L2
  • L2 gene engineering:
    • Type: Recombinant protein preparation
    • Description: The L2 genes were subcloned into the pET28a vector (Novagen, San Diego, CA) and the resulting hexahistidine (6His)-tagged recombinant polypeptides expressed in E coli BL21 (Rosetta cells; Novagen). The recombinant L2 polypeptides were affinity purified by binding to a nickel–nitrilotriacetic acid column (Qiagen, Valencia, CA) in 8 M urea (using the QiaExpressionist standard purification protocol for denaturing conditions) and then dialyzed in cassettes (Pierce, Rockland, NJ) against phosphate-buffered saline (PBS, 137 mM NaCl, 12 mM phosphate, 2.7 mM KCl) (Jagu et al., 2009).
    • Detailed Gene Information: Click Here.
  • Adjuvant: aluminum vaccine adjuvant
  • Immunization Route: Subcutaneous injection
  • Vaccine Ontology ID: VO_0004803
  • Type: Recombinant vector vaccine
  • Status: Research
  • Host Species for Licensed Use: Baboon
  • E7 gene engineering:
    • Type: Recombinant vector construction
    • Description: The E7 gene is inserted into the vector of Listeria monocytogenes, strain LM1-2 (Jia et al., 2012).
    • Detailed Gene Information: Click Here.
  • Preparation: The E7 fragment was amplified with PCR then cloned into the chromosome of L. monocytogenes (Jia et al., 2012).
  • Immunization Route: Intramuscular injection (i.m.)
Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response

Mouse Response

  • Vaccine Immune Response Type: VO_0000286
  • Efficacy: 100% of mice receiving CRT/E7 DNA vaccination remained tumor-free 60 days after TC-1 challenge. In contrast, all of the unvaccinated mice and mice receiving plasmid without insert, CRT, or E7 DNA developed tumors within 15 days after tumor challenge (Cheng et al., 2001).

Mouse Response

  • Vaccine Immune Response Type: VO_0000286
  • Efficacy: Vaccination with the modified E7IR construct was able to significantly reduce tumor volume and enhance survival in both prophylactic and therapeutic experiments in mice compared to the WT E7 gene. Vaccination with E7IR also prevented tumor formation; after challenge with tumor cells, by day 33 all naïve and vector vaccinated mice were tumor bearing, 3/5 mice vaccinated with the WT construct were tumor bearing and none of the animals vaccinated with the E7IR construct were tumor bearing. As a result, vaccination with the E7IR construct promoted 100% survival in these mice to 57 days (Brinkman et al., 2007).

Mouse Response

  • Vaccine Immune Response Type: VO_0000286
  • Efficacy: Immunization of C57BL/6 mice with E7SH DNA induced E7-specific CTL and also conveyed protection against E7-positive syngeneic tumor cells. Mice were challenged with 2 doses of TC-1 cells 100 days apart, and there was no tumor growth in any of the mice up to 80 days post-rechallenge, showing that a single injection of E7SH DNA had induced a long-lasting protective immunity (Osen et al., 2001).

Mouse Response

  • Vaccine Immune Response Type: VO_0000286
  • Efficacy: Immunization with DNA vaccines expressing hCRTE6E7 and hCRTE6E7L2 induced a higher percentage of tumor-free mice compared to immunization with the other DNA vaccines (Kim et al., 2008).

Mouse Response

  • Vaccine Immune Response Type: VO_0000286
  • Efficacy: Mice were challenged with a syngeneic melanoma cell line, engineered to express the HPV16-L1 protein, tumours in vaccinated animals showed slower growth rate, correlated directly with a longer survival of mice. The results suggest that the L1-based DNA vaccine may be useful for the prevention of primary infections by HPV16 (Rocha-Zavaleta et al., 2002).

Mouse Response

  • Vaccine Immune Response Type: VO_0000286
  • Efficacy: Animals immunized with pE7 alone showed almost complete protection from TC-1 tumour challenge. However, animals immunized with pE7 plus pIL-12 displayed a complete loss of antitumour resistance in a manner similar to control groups (Sin, 2009).

Mouse Response

  • Host Strain: C57BL/6
  • Vaccination Protocol: Gold particles coated with pNGVL4a, pNGVL4a-E6 or pNGVL4a-E6/opt were delivered to the shaved abdominal regions of mice by using a helium-driven gene gun (Bio-Rad Laboratories Inc., Hercules, Calif.) with a discharge pressure of 400 lb/in^2. Mice were immunized with 2 lg of the DNA vaccine and received two boosts with the same dose at 1-week interval. Splenocytes were harvested 1 week after the last vaccination (Lin et al., 2006).
  • Challenge Protocol: One week after the last vaccination, mice were challenged with 5 x104 TC-1 tumor cells mouse subcutaneously in the right leg and monitored once a week by inspection and palpation (Lin et al., 2006).
  • Efficacy: C57BL/6 mice vaccinated with pNGVL4a-E6/opt are able to generate potent protective and therapeutic antitumor effects against challenge with E6-expressing tumor cell line, TC-1 of HPV (Lin et al., 2006).

Mouse Response

  • Host Strain: C57BL/6
  • Vaccination Protocol: Female C57BL/6 mice (8–12 weeks old) were purchased from the Animal Center of Chinese Academy of Medical Science (Beijing, China) and held under specific pathogen-free conditions. Mice were subcutaneously injected either with 200 μg E7p/mIgG. HCCR, 20 μg E7p, 20 μg E7p plus 180 μg mIgG HCCR or 180 μg mIgG HCCR, respectively. All proteins were dissolved in PBS to achieve similar molar levels of E738–61 peptide in all cases. All four immunogens were mixed with an equal volume of Freund's incomplete adjuvant before vaccination. The total injection volume was 200 μl/mouse. All the mice were boosted with the same dose of immunogen solution using the same adjuvant after 3 weeks (Qin et al., 2005).
  • Challenge Protocol: Female C57BL/6 mice (8–12 weeks old) were used for evaluating the protection ability of the chimeric protein against tumor challenge. Four groups (n = 5) of C57BL/6 mice were immunized twice on Day 0 and 21 with 200 μg E7p/mIgG HCCR, 20 μg E7p, 20 μg E7p plus 180 μg mIgG HCCR or 180 μg mIgG HCCR, respectively. After a week, all mice in the four groups were challenged with 5 × 104 TC-1 tumor cells subcutaneously. Following the TC-1 cells challenge, tumor development in mice was monitored every week until the death of mice (Qin et al., 2005).
  • Efficacy: Researchers combined the HPV16 E7 peptide(38-61) with a murine IgG heavy chain constant region to construct a chimeric protein compound. The chimeric vaccine candidate was able to effectively protect mice against the challenge of HPV16-positive tumor cells, and to eradicate HPV16-expressing tumors in mice (Qin et al., 2005).

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: Balb/c mice (n=120, from NCI, Frederick, MD) were vaccinated in groups of five mice three times at 2-week intervals by subcutaneous injection with 10 μg of HPV-16 or HPV-45 L1 VLP, or the adjuvants alum (1.3 mg), or 1018 ISS alone (10 μg/mouse), or 25 μg of recombinant L2-based antigens including 11-200 × 1, 11-200 × 3, 1-88 × 1, 11-88 × 5, 17-36 × 22, or HPV-16 L2 17-36 peptide prepared by chemical synthesis (Sigma Aldrich, St Louis, MO) in the formulations indicated: PBS alone, or alum alone (1.3 mg), or 1018 ISS alone (10 μg/mouse), or 25 μg 11-200 × 3 alone, or formulated with alum (1.3 mg), or with 1018 ISS (10 μg/mouse), or with GPI-0100 (at either 50 or 200 μg/mouse), or with GPI-0100 (50 μg/mouse) + Tween-40 (1 mg/mouse), or with alum and 1018 ISS (10 μg/mouse) (Jagu et al., 2009).
  • Challenge Protocol: All mice were anesthetized, and a patch of skin on their ventral torso was shaved with an electric razor while taking care not to traumatize the epithelium, before challenge by application of approximately 3 × 109 HPV-16 pseudovirion particles (100 ng protein) that encapsidated pYLUC, a plasmid carrying a luciferase gene that would be expressed upon pseudoinfection (http://home.ccr.cancer.gov/lco/) in 10 μL 0.6% carboxymethylcellulose (Sigma Aldrich) to the patch of shaved skin on each mouse (Jagu et al., 2009).
  • Efficacy: Antibody responses of mice (n = 120) and rabbits (n = 23) to vaccination with HPV-16 amino-terminal L2 polypeptides or multitype L2 fusion proteins were compared. 11-200 x 3 formulated in GPI-0100 adjuvant or alum with 1018 ISS protected mice against HPV-16 challenge (reduction in HPV-16 infection vs phosphate-buffered saline control, P < .001) 4 months after vaccination as well as HPV-16 L1 VLPs (Jagu et al., 2009).

Mouse Response

  • Host Strain: C57BL/6
  • Vaccination Protocol: Mice were vaccinated in both a prophylactic (where the mice were immunized and then presented with a pathogenic challenge) and therapeutic (where the mice already had tumors and then were injected with the vaccine vector) setting (Jia et al., 2012).
  • Vaccine Immune Response Type: VO_0000287
  • Challenge Protocol: In the prophylactic assay, "mice were challenged with TC-1 cells on day 4 after the second immunization and were observed for tumor development" and in the mice vaccinated with LM1-2-E7, 87.5% showed no signs of a tumor until after day 50 (Jia et al., 2012).
  • Efficacy: The LM1-2-E7 vaccine vector was shown to elicit protection against TC-1 tumor cells in the prophylactic challenges (Jia et al., 2012).
References References References References References References References References References References
Cheng et al., 2001: Cheng WF, Hung CF, Chai CY, Hsu KF, He L, Ling M, Wu TC. Tumor-specific immunity and antiangiogenesis generated by a DNA vaccine encoding calreticulin linked to a tumor antigen. The Journal of clinical investigation. 2001; 108(5); 669-678. [PubMed: 11544272].
Brinkman et al., 2007: Brinkman JA, Xu X, Kast WM. The efficacy of a DNA vaccine containing inserted and replicated regions of the E7 gene for treatment of HPV-16 induced tumors. Vaccine. 2007; 25(17); 3437-3444. [PubMed: 17241713].
Osen et al., 2001: Osen W, Peiler T, Ohlschläger P, Caldeira S, Faath S, Michel N, Müller M, Tommasino M, Jochmus I, Gissmann L. A DNA vaccine based on a shuffled E7 oncogene of the human papillomavirus type 16 (HPV 16) induces E7-specific cytotoxic T cells but lacks transforming activity. Vaccine. 2001; 19(30); 4276-4286. [PubMed: 11457555].
Kim et al., 2008: Kim D, Gambhira R, Karanam B, Monie A, Hung CF, Roden R, Wu TC. Generation and characterization of a preventive and therapeutic HPV DNA vaccine. Vaccine. 2008; 26(3); 351-360. [PubMed: 18096279].
Rocha-Zavaleta et al., 2002: Rocha-Zavaleta L, Alejandre JE, Garcia-Carranca A. Parenteral and oral immunization with a plasmid DNA expressing the human papillomavirus 16-L1 gene induces systemic and mucosal antibodies and cytotoxic T lymphocyte responses. Journal of medical virology. 2002; 66(1); 86-95. [PubMed: 11748663].
Sin, 2009: Sin JI. Suppression of antitumour protective cytotoxic T lymphocyte responses to a human papillomavirus 16 E7 DNA vaccine by coinjection of interleukin-12 complementary DNA: involvement of nitric oxide in immune suppression. Immunology. 2009; 128(1 Suppl); e707-717. [PubMed: 19740332].
Lin et al., 2006: Lin CT, Tsai YC, He L, Calizo R, Chou HH, Chang TC, Soong YK, Hung CF, Lai CH. A DNA vaccine encoding a codon-optimized human papillomavirus type 16 E6 gene enhances CTL response and anti-tumor activity. Journal of biomedical science. 2006; 13(4); 481-488. [PubMed: 16649071].
Qin et al., 2005: Qin Y, Wang XH, Cui HL, Cheung YK, Hu MH, Zhu SG, Xie Y. Human papillomavirus type 16 E7 peptide(38-61) linked with an immunoglobulin G fragment provides protective immunity in mice. Gynecologic oncology. 2005; 96(2); 475-483. [PubMed: 15661238].
Jagu et al., 2009: Jagu S, Karanam B, Gambhira R, Chivukula SV, Chaganti RJ, Lowy DR, Schiller JT, Roden RB. Concatenated multitype L2 fusion proteins as candidate prophylactic pan-human papillomavirus vaccines. Journal of the National Cancer Institute. 2009; 101(11); 782-792. [PubMed: 19470949].
Jia et al., 2012: Jia Y, Yin Y, Duan F, Fu H, Hu M, Gao Y, Pan Z, Jiao X. Prophylactic and therapeutic efficacy of an attenuated Listeria monocytogenes-based vaccine delivering HPV16 E7 in a mouse model. International journal of molecular medicine. 2012; 30(6); 1335-1342. [PubMed: 23027427].