Human Papillomavirus
10566
HPV infection is limited to the basal cells of stratified epithelium, the only tissue in which they replicate.The virus can not bind to live tissue; instead it infects epithelial tissues through micro-abrasions or other epithelial trauma that exposes segments of the basement membrane.The infectious process is slow, taking 12–24 h for initiation of transcription. It's believed that involved antibodies play a major neutralizing role while the virions still reside on the basement membrane and cell surfaces (Wiki: HPV).
HPV infection
Human Papilloma Virus (HPV) is a sexually transmitted virus. It is usually found in the genital tract and causes various lesions at the mucosae of both men and women. It is considered as a causative factor of cervical cancer even if all women infected by HPV will not develop the disease (Panagiotis et al., 2008). HPV) infection is the most common sexually transmitted infection in the USA. It has been estimated suggest that more than 80% of sexually active women will have acquired genital HPV by age 50 years (Huang, 2008).
Baboon
Papio cynocephalus
9556
Bank vole
Clethrionomys glareolus
447135
Bear
Ursus americanus
9643
Birds
Passeroidea
175121
Brown Trout
Salmo trutta
8032
Buffalo
Bison bison
9901
Carnivores
Vulpes
9625
Cat
Felis catus
9685
Catfishes
Siluriformes
7995
Cattle
Bos taurus
9913
Chicken
Gallus gallus
9031
Chimpanzee
Pan troglodytes
9598
chinchillas
Chinchillidae
10150
Copper Pheasant
Syrmaticus soemmerringii
9067
Deer
Cervus elaphus
9860
Deer mouse
Peromyscus maniculatus
10042
Dog
Canis familiaris
9615
Ducks
Anas
8835
Ferret
Mustela putorius furo
9669
Fish
Hyperotreti
117565
Gerbil
Gerbillina
10045
Goat
Capra hircus
9925
Gray wolf
Canis lupus
9612
Guinea pig
Cavia porcellus
10141
Hamster
Mesocricetus auratus
10036
Horse
Equus caballus
9796
Human
Homo sapiens
9606
Macaque
Macaca fascicularis
9541
Mongolian Gerbil
Meriones unguiculatus
10047
Monkey
Platyrrhini
9479
Mouse
Mus musculus
10090
None
None
Parrot
Psittacidae
9224
Pig
Sus scrofa
9823
Rabbit
Oryctolagus cuniculus
9986
Rainbow trout
Oncorhynchus mykiss
8022
Rat
Rattus
10114
Raven
Corvus corax
56781
sei whale
Balaenoptera borealis
9768
Sheep
Ovis aries
9940
Squirrel
Spermophilus richardsonii
37591
Tree shrew
Tupaiidae
9393
Trouts, salmons & chars
Salmoninae
504568
Turkey
Meleagris gallopavo
9103
Vole
Microtus ochrogaster
79684
Water buffalo
Bubalus bubalis
391902
11-valent recombinant human papilloma virus vaccine (Hansenula polymorpha)
ChinaVaccineSerum
Virus Like Particle
Clinical trial
Intramuscular injection (i.m.)
Intramuscular injection (i.m.)
Recombinant protein preparation
(Liu et al., 2015)According to the 0, 2, and 6 months immunization program, intramuscular injection of the upper arm deltoid muscle, 3 doses of the experiment vaccine
AAVLP(HPV16/31L2)
Recombinant vector vaccine
Clinical trial
Intramuscular injection (i.m.)
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).
Generated AAVLPs displaying HPV16 L2 epitopes in position 587 and HPV31 L2 epitopes in position 453. (Nieto et al., 2012).
Intramuscular injection (i.m.)
Adeno-associated virus serotype 2 (AAV2) capsids
Recombinant protein preparation
L2 proteins harbors several regions that can be targeted by neutraliizing antibodies (Nieto et al., 2012).
Recombinant protein preparation
Insertion of L2 HPV31 into VP3 at positions 583 and 453.
Balb/c and C57BL/6
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).
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).
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)
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)
ADXS11-001
Neoadjuvant ADXS11-001 (ADXS-HPV)
Advaxis
Live, attenuated vaccine
Clinical trial
[Ref5589:Galicia-Carmona et al., 2021]LM vector
Intravenous injection (i.v.)
(Galicia-Carmona et al., 2021) LM based vectors infect antigen presenting cells and secrete HPV-LLO fusion proteins with the APC cytoplasm. These proteins are processed and presented to cytotoxic T lymphocytes (CTL), thus generating a new population of CTLs specific to HPV antigens. These HPV-specific CTLs destroy HPV infected cells.
(Galicia-Carmona et al., 2021)LLO acts as a potent adjuvant when incorporated into NA vaccines.
(Galicia-Carmona et al., 2021)They prepared two recombinant Lm strains, one expressing the HPV-16 E7 protein without attempting to modify the LLO molecule (Lm-E7), and the second expressed E7 as a non-hemolytic LLO-bound fusion protein (Lm-LLO-E7).
Intravenous injection (i.v.)
(Galicia-Carmona et al., 2021)Antigen presenting cell alert the adaptive immune response of the presence of Lm through the major
histocompatibility complex (MHC) molecules by two different routes. LM antigens from bacteria. tumor antigen-specific cytotoxic CD8
Recombinant protein preparation
The tumor-associated antigen (HPV16 E7) is expressed via live attenuated Listeria monocytogenes-listeriolysin O (Lm-LLO), which helped stimulate the antigen-specific immune responses (Galicia-Carmona et al., 2021).
Cervarix
Human Papillomavirus Bivalent (Types 16 and 18) Vaccine, Recombinant
Cervarix
GlaxoSmithKline Biologicals
VO_0011559
Inactivated or "killed" vaccine
Licensed
Intramuscular injection (i.m.)
USA
AS04
Store refrigerated between 2º and 8ºC (36º and 46ºF). Do not freeze.
prepared by combining the adsorbed VLPs of each HPV type together with the AS04 adjuvant system in sodium chloride, sodium dihydrogen phosphate dihydrate, and water for Injection (FDA: Cevarix).
Intramuscular injection (i.m.)
Gardasil
Human Papillomavirus Quadrivalent (Types 6, 11, 16, 18) Vaccine, Recombinant
Gardasil
Merck & Co., Inc.
VO_0000049
Subunit vaccine
Licensed
Intramuscular injection (i.m.)
USA (License #0002)
Indication: Vaccination in females 9 to 26 years of age for prevention of the following diseases caused by Human Papillomavirus (HPV) Types 6, 11, 16, and 18: cervical cancer, and genital warts (condyloma acuminata), and the following precancerous or dysplastic lesions: cervical adenocarcinoma in situ (AIS), cervical intraepithelial neoplasia (CIN) grade 2 and grade 3, vulvar intraepithelial neoplasia (VIN) grade 2 and grade 3, vaginal intraepithelial neoplasia (VaIN) grade 2 and grade 3, cervical intraepithelial neoplasia (CIN) grade 1 (FDA: Gardasil). In June 2006, the US Food and Drug Administration licensed this first vaccine to prevent cervical cancers and other diseases in women. This quadrivalent vaccine protects against HPV-6, HPV-11, HPV-16, and HPV-18, which are responsible for 70% of cervical cancers and 90% of genital warts (Huang, 2008).
GARDASIL should be refrigerated at 2 to 8 degrees Celcius. Do not freeze. Protect from light.
GARDASIL is a non-infectious recombinant quadrivalent vaccine prepared from the purified virus-like particles (VLPs) of the major capsid (L1) protein of HPV Types 6, 11, 16, and 18. The L1 proteins are produced by separate fermentations in recombinant Saccharomyces cerevisiae and self-assembled into VLPs. The fermentation process involves growth of S. cerevisiae on chemically-defined fermentation media which include vitamins, amino acids, mineral salts, and carbohydrates. The VLPs are released from the yeast cells by cell disruption and purified by a series of chemical and physical methods. The purified VLPs are adsorbed on preformed aluminum-containing adjuvant (Amorphous Aluminum Hydroxyphosphate Sulfate). The quadrivalent HPV VLP vaccine is a sterile liquid suspension that is prepared by combining the adsorbed VLPs of each HPV type and additional amounts of the aluminum-containing adjuvant and the final purification buffer. GARDASIL is a sterile suspension for intramuscular administration (FDA: Gardasil).
Intramuscular injection (i.m.)
Virus-like particles (VLPs) of the major capsid (L1) protein of HPV Types 6, 11, 16, and 18.
In clinical studies it was discovered that around 99% of girls and women who were immunized with GARDASIL became anti-HPV 6, anti-HPV 11, anti-HPV 16 and anti-HPV 18 seropositive by 1 month after the third and final dose(FDA: Gardasil).
In 5 clinical trials, subjects were administered with GARDASIL or AAHS (Amorphous Aluminum Hydroxyphosphate) control or saline placebo. The subjects included 5088 girls and women ages 9 to 26 years (FDA: Gardasil).
Most common side effect of immunization was headache. Other side effects include: fever, nausea, dizziness, injection site pain and swelling.
Gardasil 9
Human Papillomavirus 9-valent Vaccine, Recombinant
Gardasil 9
Merck & Co., Inc.
Subunit vaccine
Licensed
Intramuscular injection (i.m.)
USA, Canada
9-valent derivative of Gardasil
AAHSA
Intramuscular injection (i.m.)
Human papillomavirus DNA vaccine CRT/E7 DNA
VO_0004331
DNA vaccine
Research
pCDNA3 [Ref2170:Cheng et al., 2001]
Intramuscular injection (i.m.)
Intramuscular injection (i.m.)
DNA vaccine construction
Vector pCDNA3 expressed E7 protein of HPV 16 and 18 (Cheng et al., 2001).
VO_0000286
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).
Human papillomavirus DNA vaccine E7IR
VO_0004332
DNA vaccine
Research
APL023 [Ref2173:Brinkman et al., 2007]
Gene gun
Gene gun
DNA vaccine construction
Vector APL023expressed the E7 gene (Brinkman et al., 2007).
VO_0000286
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).
Human papillomavirus DNA vaccine E7SH DNA
VO_0004333
DNA vaccine
Research
pCDNA3 [Ref2174:Osen et al., 2001]
Intramuscular injection (i.m.)
Intramuscular injection (i.m.)
DNA vaccine construction
Vector pCDNA3 expressed the E7 oncogene of the human papillomavirus type 16 (HPV 16) (Osen et al., 2001).
VO_0000286
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).
Human papillomavirus DNA vaccine hCRTE6E7L2 DNA encoding CRT linked to E6, E7 and L2
VO_0004475
DNA vaccine
Research
pNGVL4a vector (National Gene Vector lab) [Ref2412:Kim et al., 2008]
Gene gun
Gene gun
DNA vaccine construction
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).
DNA vaccine construction
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).
Recombinant protein preparation
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).
DNA vaccine construction
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).
VO_0000286
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).
Human papillomavirus DNA vaccine pC16-L1 encoding L1
VO_0004330
DNA vaccine
Research
pCDNA3 [Ref2169:Rocha-Zavaleta et al., 2002]
Intramuscular injection (i.m.)
Intramuscular injection (i.m.)
DNA vaccine construction
Vector pCDNA3 expressed L1 (Rocha-Zavaleta et al., 2002).
VO_0000286
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).
Human papillomavirus DNA vaccine Pe7(pcDNA3-Sig/sE7/LAMP) encoding E7
VO_0004329
DNA vaccine
Research
pcDNA3 [Ref2167:Sin, 2009]
Intramuscular injection (i.m.)
Intramuscular injection (i.m.)
DNA vaccine construction
Vector pcDNA3 expressed HPV oncogenic proteins E7 (Sin, 2009).
VO_0000286
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).
Human papillomavirus DNA vaccine pNGVL4a-E6/opt
VO_0011480
DNA vaccine
Research
pNGVL4a
Intradermal injection (i.d.)
Intradermal injection (i.d.)
Human papillomavirus E6
DNA vaccine construction
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).
C57BL/6
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).
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).
One week after the last vaccination, mice were challenged with 5 x10^4 TC-1 tumor cells mouse subcutaneously in the right leg and monitored once a week by inspection and palpation (Lin et al., 2006).
Human papillomavirus DNA vaccine VlJns-Ll encoding L1
VO_0004328
DNA vaccine
Research
VlJns [Ref2166:Donnelly et al., 1996]
Intramuscular injection (i.m.)
Intramuscular injection (i.m.)
DNA vaccine construction
Vector VlJns expressed the major viral capsid protein L1 (Donnelly et al., 1996).
VO_0000286
Immunization with plasmid DNA encoding L1 elicited conformationally specific neutralizing antibodies and provided immunity against papilloma formation upon challenge with CRPV (Donnelly et al., 1996).
Human papillomavirus E7 protein vaccine
VO_0011395
Subunit vaccine
Research
Subcutaneous injection
Freund's incomplete adjuvant
Subcutaneous injection
Human papillomavirus E7
Recombinant protein preparation
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).
C57BL/6
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).
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).
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 × 10^4 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).
Human papillomavirus L2 protein vaccine
VO_0011397
Subunit vaccine
Research
Subcutaneous injection
GPI-0100 adjuvant or alum
Subcutaneous injection
Human papillomavirus L2
Recombinant protein preparation
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).
BALB/c
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).
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).
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 × 10^9 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).
LM1-2-E7
VO_0004803
Recombinant vector vaccine
Research
Intramuscular injection (i.m.)
The E7 fragment was amplified with PCR then cloned into the chromosome of L. monocytogenes (Jia et al., 2012).
Intramuscular injection (i.m.)
Recombinant vector construction
The E7 gene is inserted into the vector of Listeria monocytogenes, strain LM1-2 (Jia et al., 2012).
C57BL/6
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).
VO_0000287
The LM1-2-E7 vaccine vector was shown to elicit protection against TC-1 tumor cells in the prophylactic challenges (Jia et al., 2012).
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).
MEDI0457
MEDI 0457
CELLECTRA (Inovio Pharmaceuticals, San Diego, CA)
DNA vaccine
Clinical trial
Intramuscular injection (i.m.)
(Hasan et al., 2020)MEDI0457 (INO-3112) is a DNA-based vaccine targeting E6 and E7 of HPV-16/18 that is coinjected with an IL-12 plasmid followed by electroporation with the CELLECTRA 5P device. At 2 to 4 weeks after chemoradiation, patients with newly diagnosed stage IB1-IVA (cohort 1) or persistent/recurrent (cohort 2) cervical cancers were treated with 4 immunizations of MEDI0457 every 4 weeks
Intramuscular injection (i.m.)
(Hasan et al., 2020)E6 and E7 serve as non self antigens
DNA vaccine construction
E6 gene is inserted into a DNA vaccine plasmid, which allows the expression of the E6 protein.
Recombinant protein preparation
The E7 gene is inserted into a DNA vaccine plasmid, which allows the expression of the E7 protein.
V503
Human Papillomavirus 9vHPV (6,11,16,18,31,33,45,52,58) Nonvalent Vaccine, Recombinant
Gardasil
Merck Sharp & Dohme LLC
Recombinant vector vaccine
Licensed
Intramuscular injection (i.m.)
USA
Instead of a 4VHPV, this vaccine is a 9 valent HPV vaccine providing more protection.
Aluminum hydroxyphosphate sulfate (AAHS)
Intramuscular injection (i.m.)
Participants (n = 600) were randomized to receive 9vHPV or qHPV vaccines on day 1, month 2 and month 6.
immune responses to HPV 31/33/45/52/58, a 3-dose regimen of the 9vHPV vaccine elicited a similar immune response to HPV 6/11/16/18 when compared with the qHPV vaccine in girls aged 9–15 years after month 7 (Vesikari et al., 2015).
CRTC
Homo sapiens
1905911
CDD:306718
9606
?
calreticulin
4.06
46534.41
464
constructed at LLNL from flow-sorted chromosomes from hybrid 5HL2-B, which carries chromosome 19 as its only human chromosome
>AAB51176.1 calreticulin [Homo sapiens]
MLLSVPLLLGLLGLAVAEPAVYFKEQFLDGDGWTSRWIESKHKSDFGKFVLSSGKFYGDEEKDKGLQTSQ
DARFYALSASFEPFSNKGQTLVVQFTVKHEQNIDCGGGYVKLFPNSLDQTDMHGDSEYNIMFGPDICGPG
TKKVHVIFNYKGKNVLINKDIRCKDDEFTHLYTLIVRPDNTYEVKIDNSQVESGSLEDDWDFLPPKKIKD
PDASKPEDWDERAKIDDPTDSKPEDWDKPEHIPDPDAKKPEDWDEEMDGEWEPPVIQNPEYKGEWKPRQI
DNPDYKGTWIHPEIDNPEYSPDPSIYAYDNFGVLGLDLWQVKSGTIFDNFLITNDEAYAEEFGNETWGVT
KAAEKQMKDKQDEEQRLKEEEEDKKRKEEEEAEDKEDDEDKDEDEEDEEDKEEDEEEDVPGQAKDEL
Protective antigen
E6 HPV 18
Human Papillomavirus
AAP20594
CDD:332494
333761
E6 protein
8.56
18681.84
216
Early Protein (E6); cl27673
>AAP20594.1 E6 protein [Human papillomavirus type 18]
MARFEDPTRRPYKLPDLCTELNTSLQDIEITCVYCKTVLELTEVFEFAFKDLFVVYRDSIPHAACHKCID
FYSRIRELRHYSDSVYGDTLEKLTNTGLYNLLIRCLRCQKPLNPAEKLRHLNEKRRFHNIAGHYRGQCHS
CCNRARQERLQRRRETQV
Protective antigen
[Ref5014:Khan et al., 2017]
E6 Type 16
Human papillomavirus type 16
VO_0011107
1489078
9627104
HpV16gp1
AB663688
NP_041325
333760
7124
7600
+
transforming protein E6
8.97
18789.29
158
E6 ORF from 65 to 559; putative
>NC_001526.4:7124-7600 Human papillomavirus type 16, complete genome
TATGCACCAAAAGAGAACTGCAATGTTTCAGGACCCACAGGAGCGACCCAGAAAGTTACCACAGTTATGC
ACAGAGCTGCAAACAACTATACATGATATAATATTAGAATGTGTGTACTGCAAGCAACAGTTACTGCGAC
GTGAGGTATATGACTTTGCTTTTCGGGATTTATGCATAGTATATAGAGATGGGAATCCATATGCTGTATG
TGATAAATGTTTAAAGTTTTATTCTAAAATTAGTGAGTATAGACATTATTGTTATAGTTTGTATGGAACA
ACATTAGAACAGCAATACAACAAACCGTTGTGTGATTTGTTAATTAGGTGTATTAACTGTCAAAAGCCAC
TGTGTCCTGAAGAAAAGCAAAGACATCTGGACAAAAAGCAAAGATTCCATAATATAAGGGGTCGGTGGAC
CGGTCGATGTATGTCTTGTTGCAGATCATCAAGAACACGTAGAGAAACCCAGCTGTA
>NP_041325.1 transforming protein E6 [Human papillomavirus type 16]
MHQKRTAMFQDPQERPRKLPQLCTELQTTIHDIILECVYCKQQLLRREVYDFAFRDLCIVYRDGNPYAVC
DKCLKFYSKISEYRHYCYSLYGTTLEQQYNKPLCDLLIRCINCQKPLCPEEKQRHLDKKQRFHNIRGRWT
GRCMSCCRSSRTRRETQL
Protective antigen
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 [Ref1121:Lin et al., 2006].
E7 Type 16
Human papillomavirus type 16
VO_0011105
1489079
9627105
HpV16gp2
AB663783
NP_041326
333760
7603
7899
+
transforming protein E7
3.97
10624.95
98
E7 ORF from 544 to 858; putative
>NC_001526.4:7603-7899 Human papillomavirus type 16, complete genome
CATGCATGGAGATACACCTACATTGCATGAATATATGTTAGATTTGCAACCAGAGACAACTGATCTCTAC
TGTTATGAGCAATTAAATGACAGCTCAGAGGAGGAGGATGAAATAGATGGTCCAGCTGGACAAGCAGAAC
CGGACAGAGCCCATTACAATATTGTAACCTTTTGTTGCAAGTGTGACTCTACGCTTCGGTTGTGCGTACA
AAGCACACACGTAGACATTCGTACTTTGGAAGACCTGTTAATGGGCACACTAGGAATTGTGTGCCCCATC
TGTTCTCAGAAACCATA
>NP_041326.1 transforming protein E7 [Human papillomavirus type 16]
MHGDTPTLHEYMLDLQPETTDLYCYEQLNDSSEEEDEIDGPAGQAEPDRAHYNIVTFCCKCDSTLRLCVQ
STHVDIRTLEDLLMGTLGIVCPICSQKP
Protective antigen
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 [Ref1118:Qin et al., 2005].
L1 HPV 16
Human papillomavirus type 16
VO_0011108
1489082
1046490004
HpV16gp8
K02718
NP_041332
2R5H
333760
4774
6291
+
major capsid protein L1
8.38
53132.12
505
major capsid L1 protein; Two structural proteins are involved in papillomavirus capsid formation, a major (L1) and a minor (L2) protein; L1 forms the pentameric assembly unit of the viral shell while L2 mediates several facets of viral entry including endosomal escape after uncoating
>NC_001526.4:4774-6291 Human papillomavirus type 16, complete genome
GATGTCTCTTTGGCTGCCTAGTGAGGCCACTGTCTACTTGCCTCCTGTCCCAGTATCTAAGGTTGTAAGC
ACGGATGAATATGTTGCACGCACAAACATATATTATCATGCAGGAACATCCAGACTACTTGCAGTTGGAC
ATCCCTATTTTCCTATTAAAAAACCTAACAATAACAAAATATTAGTTCCTAAAGTATCAGGATTACAATA
CAGGGTATTTAGAATACATTTACCTGACCCCAATAAGTTTGGTTTTCCTGACACCTCATTTTATAATCCA
GATACACAGCGGCTGGTTTGGGCCTGTGTAGGTGTTGAGGTAGGTCGTGGTCAGCCATTAGGTGTGGGCA
TTAGTGGCCATCCTTTATTAAATAAATTGGATGACACAGAAAATGCTAGTGCTTATGCAGCAAATGCAGG
TGTGGATAATAGAGAATGTATATCTATGGATTACAAACAAACACAATTGTGTTTAATTGGTTGCAAACCA
CCTATAGGGGAACACTGGGGCAAAGGATCCCCATGTACCAATGTTGCAGTAAATCCAGGTGATTGTCCAC
CATTAGAGTTAATAAACACAGTTATTCAGGATGGTGATATGGTTGATACTGGCTTTGGTGCTATGGACTT
TACTACATTACAGGCTAACAAAAGTGAAGTTCCACTGGATATTTGTACATCTATTTGCAAATATCCAGAT
TATATTAAAATGGTGTCAGAACCATATGGCGACAGCTTATTTTTTTATTTACGAAGGGAACAAATGTTTG
TTAGACATTTATTTAATAGGGCTGGTACTGTTGGTGAAAATGTACCAGACGATTTATACATTAAAGGCTC
TGGGTCTACTGCAAATTTAGCCAGTTCAAATTATTTTCCTACACCTAGTGGTTCTATGGTTACCTCTGAT
GCCCAAATATTCAATAAACCTTATTGGTTACAACGAGCACAGGGCCACAATAATGGCATTTGTTGGGGTA
ACCAACTATTTGTTACTGTTGTTGATACTACACGCAGTACAAATATGTCATTATGTGCTGCCATATCTAC
TTCAGAAACTACATATAAAAATACTAACTTTAAGGAGTACCTACGACATGGGGAGGAATATGATTTACAG
TTTATTTTTCAACTGTGCAAAATAACCTTAACTGCAGACGTTATGACATACATACATTCTATGAATTCCA
CTATTTTGGAGGACTGGAATTTTGGTCTACAACCTCCCCCAGGAGGCACACTAGAAGATACTTATAGGTT
TGTAACATCCCAGGCAATTGCTTGTCAAAAACATACACCTCCAGCACCTAAAGAAGATCCCCTTAAAAAA
TACACTTTTTGGGAAGTAAATTTAAAGGAAAAGTTTTCTGCAGACCTAGATCAGTTTCCTTTAGGACGCA
AATTTTTACTACAAGCAGGATTGAAGGCCAAACCAAAATTTACATTAGGAAAACGAAAAGCTACACCCAC
CACCTCATCTACCTCTACAACTGCTAAACGCAAAAAACGTAAGCTGTA
>NP_041332.2 major capsid protein L1 [Human papillomavirus type 16]
MSLWLPSEATVYLPPVPVSKVVSTDEYVARTNIYYHAGTSRLLAVGHPYFPIKKPNNNKILVPKVSGLQY
RVFRIHLPDPNKFGFPDTSFYNPDTQRLVWACVGVEVGRGQPLGVGISGHPLLNKLDDTENASAYAANAG
VDNRECISMDYKQTQLCLIGCKPPIGEHWGKGSPCTNVAVNPGDCPPLELINTVIQDGDMVDTGFGAMDF
TTLQANKSEVPLDICTSICKYPDYIKMVSEPYGDSLFFYLRREQMFVRHLFNRAGTVGENVPDDLYIKGS
GSTANLASSNYFPTPSGSMVTSDAQIFNKPYWLQRAQGHNNGICWGNQLFVTVVDTTRSTNMSLCAAIST
SETTYKNTNFKEYLRHGEEYDLQFIFQLCKITLTADVMTYIHSMNSTILEDWNFGLQPPPGGTLEDTYRF
VTSQAIACQKHTPPAPKEDPLKKYTFWEVNLKEKFSADLDQFPLGRKFLLQAGLKAKPKFTLGKRKATPT
TSSTSTTAKRKKRKL
Protective antigen
rAAV5, -8 and -9 vectors expressing an HPV16 L1/E7 fusion gene were generated and applied intranasally for combined prophylactic and therapeutic vaccination of mice. Vaccination with the rAAV vectors led to a significant protection of animals against a challenge with different HPV tumour cell lines [Ref1122:Nieto et al., 2009].
L1 HPV 52
AAY57811.1
GQ472848
ACX32362
CDD:420110
10618
?
L1
5.31
28729.71
324
L1 (late) protein; cl23949
>AAY57811.1 L1, partial [human papillomavirus 52]
ACTGLEIGRGQPLGVGISGHPLLNKFDDTETSNKYAGKPGIDNRECLSMDYKQTQLCILGCKPPIGEHWG
KGTPCNNNSGNPGDCPPLQLINSVIQDGDMVDTGFGCMDFNTLQASKSDVPIDICSSVCKYPDYLQMASE
PYGDSLFFFLRREQMFVRHFFNRAGTLGDPVPGDLYIQGSNSGNTATVQSSAFFPTPSGSMVTSESQLFN
KPYWLQRAQGHNNGICWGNQLFVTVVDTTRSTNMTLCAEVKKESTYKNENFKEYLRHGE
Protective antigen
L2 HPV 16
Human papillomavirus type 16
VO_0011106
1489081
1046490003
HpV16gp7
K02718
NP_041331
333760
3372
4793
?
minor capsid protein L2
6.31
47994.02
473
L2 ORF from 4133 to 5656; putative
>NC_001526.4:3372-4793 Human papillomavirus type 16, complete genome
AATGCGACACAAACGTTCTGCAAAACGCACAAAACGTGCATCGGCTACCCAACTTTATAAAACATGCAAA
CAGGCAGGTACATGTCCACCTGACATTATACCTAAGGTTGAAGGCAAAACTATTGCTGATCAAATATTAC
AATATGGAAGTATGGGTGTATTTTTTGGTGGGTTAGGAATTGGAACAGGGTCGGGTACAGGCGGACGCAC
TGGGTATATTCCATTGGGAACAAGGCCTCCCACAGCTACAGATACACTTGCTCCTGTAAGACCCCCTTTA
ACAGTAGATCCTGTGGGCCCTTCTGATCCTTCTATAGTTTCTTTAGTGGAAGAAACTAGTTTTATTGATG
CTGGTGCACCAACATCTGTACCTTCCATTCCCCCAGATGTATCAGGATTTAGTATTACTACTTCAACTGA
TACCACACCTGCTATATTAGATATTAATAATACTGTTACTACTGTTACTACACATAATAATCCCACTTTC
ACTGACCCATCTGTATTGCAGCCTCCAACACCTGCAGAAACTGGAGGGCATTTTACACTTTCATCATCCA
CTATTAGTACACATAATTATGAAGAAATTCCTATGGATACATTTATTGTTAGCACAAACCCTAACACAGT
AACTAGTAGCACACCCATACCAGGGTCTCGCCCAGTGGCACGCCTAGGATTATATAGTCGCACAACACAA
CAGGTTAAAGTTGTAGACCCTGCTTTTGTAACCACTCCCACTAAACTTATTACATATGATAATCCTGCAT
ATGAAGGTATAGATGTGGATAATACATTATATTTTTCTAGTAATGATAATAGTATTAATATAGCTCCAGA
TCCTGACTTTTTGGATATAGTTGCTTTACATAGGCCAGCATTAACCTCTAGGCGTACTGGCATTAGGTAC
AGTAGAATTGGTAATAAACAAACACTACGTACTCGTAGTGGAAAATCTATAGGTGCTAAGGTACATTATT
ATTATGATTTAAGTACTATTGATCCTGCAGAAGAAATAGAATTACAAACTATAACACCTTCTACATATAC
TACCACTTCACATGCAGCCTCACCTACTTCTATTAATAATGGATTATATGATATTTATGCAGATGACTTT
ATTACAGATACTTCTACAACCCCGGTACCATCTGTACCCTCTACATCTTTATCAGGTTATATTCCTGCAA
ATACAACAATTCCTTTTGGTGGTGCATACAATATTCCTTTAGTATCAGGTCCTGATATACCCATTAATAT
AACTGACCAAGCTCCTTCATTAATTCCTATAGTTCCAGGGTCTCCACAATATACAATTATTGCTGATGCA
GGTGACTTTTATTTACATCCTAGTTATTACATGTTACGAAAACGACGTAAACGTTTACCATATTTTTTTT
CAGATGTCTCTTTGGCTGCCTA
>NP_041331.2 minor capsid protein L2 [Human papillomavirus type 16]
MRHKRSAKRTKRASATQLYKTCKQAGTCPPDIIPKVEGKTIADQILQYGSMGVFFGGLGIGTGSGTGGRT
GYIPLGTRPPTATDTLAPVRPPLTVDPVGPSDPSIVSLVEETSFIDAGAPTSVPSIPPDVSGFSITTSTD
TTPAILDINNTVTTVTTHNNPTFTDPSVLQPPTPAETGGHFTLSSSTISTHNYEEIPMDTFIVSTNPNTV
TSSTPIPGSRPVARLGLYSRTTQQVKVVDPAFVTTPTKLITYDNPAYEGIDVDNTLYFSSNDNSINIAPD
PDFLDIVALHRPALTSRRTGIRYSRIGNKQTLRTRSGKSIGAKVHYYYDLSTIDPAEEIELQTITPSTYT
TTSHAASPTSINNGLYDIYADDFITDTSTTPVPSVPSTSLSGYIPANTTIPFGGAYNIPLVSGPDIPINI
TDQAPSLIPIVPGSPQYTIIADAGDFYLHPSYYMLRKRRKRLPYFFSDVSLAA
Protective antigen
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 [Ref1119:Jagu et al., 2009].
L2 HPV31
ALT54672
CDD:332973
10585
?
L2
6.29
47098.96
515
type: 31
>ALT54672.1 L2 [human papillomavirus 31]
MRSKRSTKRTKRASATQLYQTCKAAGTCPSDVIPKIEHTTIADQILRYGSMGVFFGGLGIGSGSGTGGRT
GYVPLSTRPSTVSEASIPIRPPVSIDPVGPLDPSIVSLVEESGIVDVGAPAPIPHPPTTSGFDIATTADT
TPAILDVTSVSTHENPTFTDPSVLQPPTPAETSGHLLLSSSSISTHNYEEIPMDTFIVSTNNENITSSTP
IPGVRRPARLGLYSKATQQVKVIDPTFLSAPKQLITYENPAYETVNAEESLYFSNTSHNIAPDPDFLDII
ALHRPALTSRRNTVRYSRLGNKQTLRTRSGATIGARVHYYYDISSINPAGESIEMQPLGASATTTSTLND
GLYDIYADTDFTVDTPATHNVSPSTAVQSTSAVSAYVPTNTTVPLSTGFDIPIFSGPDVPIEHAPTQVFP
FPLAPTTPQVSIFVDGGDFYLHPSYYMLKRRRKRVSYFFTDVSVAA
Protective antigen
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