VIOLIN: Vaccine Investigation and Online Information Network

Human Papillomavirus

Table of Contents

General Information
Vaccine Related Pathogen Genes
1. CRTC (Protective antigen)
2. E2 (Protective antigen)
3. E6 HPV 18 (Protective antigen)
4. E6 Type 16 (Protective antigen)
5. E7 HPV 18 (Protective antigen)
6. E7 Type 16 (Protective antigen)
7. L1 HPV 16 (Protective antigen)
8. L1 HPV 52 (Protective antigen)
9. L2 HPV 16 (Protective antigen)
10. L2 HPV 18 (Protective antigen)
11. L2 HPV31 (Protective antigen)
Vaccine Information
References

I. General Information

1. NCBI Taxonomy ID:

10566

2. Disease:

HPV infection

3. Introduction

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).

4. Microbial Pathogenesis

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).

II. Vaccine Related Pathogen Genes

1. CRTC

Gene Name : CRTC
Sequence Strain (Species/Organism) : Homo sapiens
NCBI Protein GI : 1905911
Other Database IDs : CDD:306718
Taxonomy ID : 9606
Gene Strand (Orientation) : ?
Protein Name : calreticulin
Protein pI : 4.06
Protein Weight : 46534.41
Protein Length : 464
Protein Note : constructed at LLNL from flow-sorted chromosomes from hybrid 5HL2-B, which carries chromosome 19 as its only human chromosome

Protein Sequence : Show Sequence

>AAB51176.1 calreticulin [Homo sapiens]
MLLSVPLLLGLLGLAVAEPAVYFKEQFLDGDGWTSRWIESKHKSDFGKFVLSSGKFYGDEEKDKGLQTSQ
DARFYALSASFEPFSNKGQTLVVQFTVKHEQNIDCGGGYVKLFPNSLDQTDMHGDSEYNIMFGPDICGPG
TKKVHVIFNYKGKNVLINKDIRCKDDEFTHLYTLIVRPDNTYEVKIDNSQVESGSLEDDWDFLPPKKIKD
PDASKPEDWDERAKIDDPTDSKPEDWDKPEHIPDPDAKKPEDWDEEMDGEWEPPVIQNPEYKGEWKPRQI
DNPDYKGTWIHPEIDNPEYSPDPSIYAYDNFGVLGLDLWQVKSGTIFDNFLITNDEAYAEEFGNETWGVT
KAAEKQMKDKQDEEQRLKEEEEDKKRKEEEEAEDKEDDEDKDEDEEDEEDKEEDEEEDVPGQAKDEL

Molecule Role : Protective antigen
Related Vaccine(s): Human papillomavirus DNA vaccine hCRTE6E7L2 DNA encoding CRT linked to E6, E7 and L2

2. E2

Gene Name : E2
Sequence Strain (Species/Organism) : Human Papillomavirus
NCBI Protein GI : ATD50852
Other Database IDs : CDD:278909
CDD:317681
CDD:278912
Taxonomy ID : 10566
Protein Name : E2 protein
Protein pI : 8.17
Protein Weight : 43110.78
Protein Length : 443
Protein Note : E2 (early) protein, N terminal; pfam00508

Protein Sequence : Show Sequence

>ATD50852.1 E2 protein [Human papillomavirus]
MENRESLTDRFAALQENLMTLYERDPTDLYSQIQHWDLVKKENEYYYYARKEGMTSLGMFPAPALQVSEA
KAKQAIKMLILLKSLSKSQYASEIWRLRDTSVELVLQTEPKNCFKKGPFEVEVWFDKNPQKALPYPNWQW
IYYQDQNDVWHKVKGAADYNGTYYEEVTGDRVYFALFDSEAARYGESGQWLVKYNNEIICASVSSSSRCS
YDSSNERGPSSSSIYQPETGRQSEEVSHSETRPTSTSNLRRRRGGEQGEPTTSGGAKRRRADSGGGAPSP
EEVGGTHRSVERRHLSRLGLLQAEARDPPIALITGCANSLKCWRRRTKHKYSELFLDFSTNWTWVGDKVD
NNYQSKMLIAFSSLTQREAFVKTVNLPKGATLVYGQLNSL

Molecule Role : Protective antigen
Molecule Role Annotation : (Khan et al., 2017)

3. E6 HPV 18

Gene Name : E6 HPV 18
Sequence Strain (Species/Organism) : Human Papillomavirus
NCBI Protein GI : AAP20594
Other Database IDs : CDD:332494
Taxonomy ID : 333761
Protein Name : E6 protein
Protein pI : 8.56
Protein Weight : 18681.84
Protein Length : 216
Protein Note : Early Protein (E6); cl27673

Protein Sequence : Show Sequence

>AAP20594.1 E6 protein [Human papillomavirus type 18]
MARFEDPTRRPYKLPDLCTELNTSLQDIEITCVYCKTVLELTEVFEFAFKDLFVVYRDSIPHAACHKCID
FYSRIRELRHYSDSVYGDTLEKLTNTGLYNLLIRCLRCQKPLNPAEKLRHLNEKRRFHNIAGHYRGQCHS
CCNRARQERLQRRRETQV

Molecule Role : Protective antigen
Molecule Role Annotation : (Khan et al., 2017)
Related Vaccine(s): MEDI0457

4. E6 Type 16

Gene Name : E6 Type 16
Sequence Strain (Species/Organism) : Human papillomavirus type 16
VO ID : VO_0011107
NCBI Gene ID : 1489078
NCBI Protein GI : 9627104
Locus Tag : HpV16gp1
Genbank Accession : AB663688
Protein Accession : NP_041325
Taxonomy ID : 333760
Gene Starting Position : 7124
Gene Ending Position : 7600
Gene Strand (Orientation) : +
Protein Name : transforming protein E6
Protein pI : 8.97
Protein Weight : 18789.29
Protein Length : 158
Protein Note : E6 ORF from 65 to 559; putative

DNA Sequence : Show Sequence

>NC_001526.4:7124-7600 Human papillomavirus type 16, complete genome
TATGCACCAAAAGAGAACTGCAATGTTTCAGGACCCACAGGAGCGACCCAGAAAGTTACCACAGTTATGC
ACAGAGCTGCAAACAACTATACATGATATAATATTAGAATGTGTGTACTGCAAGCAACAGTTACTGCGAC
GTGAGGTATATGACTTTGCTTTTCGGGATTTATGCATAGTATATAGAGATGGGAATCCATATGCTGTATG
TGATAAATGTTTAAAGTTTTATTCTAAAATTAGTGAGTATAGACATTATTGTTATAGTTTGTATGGAACA
ACATTAGAACAGCAATACAACAAACCGTTGTGTGATTTGTTAATTAGGTGTATTAACTGTCAAAAGCCAC
TGTGTCCTGAAGAAAAGCAAAGACATCTGGACAAAAAGCAAAGATTCCATAATATAAGGGGTCGGTGGAC
CGGTCGATGTATGTCTTGTTGCAGATCATCAAGAACACGTAGAGAAACCCAGCTGTA

Protein Sequence : Show Sequence

>NP_041325.1 transforming protein E6 [Human papillomavirus type 16]
MHQKRTAMFQDPQERPRKLPQLCTELQTTIHDIILECVYCKQQLLRREVYDFAFRDLCIVYRDGNPYAVC
DKCLKFYSKISEYRHYCYSLYGTTLEQQYNKPLCDLLIRCINCQKPLCPEEKQRHLDKKQRFHNIRGRWT
GRCMSCCRSSRTRRETQL

Molecule Role : Protective antigen
Molecule Role Annotation : 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).
Related Vaccine(s): Human papillomavirus DNA vaccine CRT/E7 DNA , Human papillomavirus DNA vaccine hCRTE6E7L2 DNA encoding CRT linked to E6, E7 and L2 , Human papillomavirus DNA vaccine pNGVL4a-E6/opt

5. E7 HPV 18

Gene Name : E7 HPV 18
Sequence Strain (Species/Organism) : Human Papillomavirus
NCBI Protein GI : AAP20595
Other Database IDs : CDD:295537
Taxonomy ID : 333761
Gene Strand (Orientation) : ?
Protein Name : E7 protein
Protein pI : 4.48
Protein Weight : 11905.36
Protein Length : 162
Protein Note : E7 protein, Early protein; cl02891

Protein Sequence : Show Sequence

>AAP20595.1 E7 protein [Human papillomavirus type 18]
MHGPKATLQDIVLHLEPQNEIPVDLLCHEQLSDSEEENDEIDGVNHQHLPARRAEPQRHTMLCMCCKCEA
RIELVVESSADDLRAFQQLFLNTLSFVCPWCASQQ

Molecule Role : Protective antigen
Molecule Role Annotation : (Khan et al., 2017)

6. E7 Type 16

Gene Name : E7 Type 16
Sequence Strain (Species/Organism) : Human papillomavirus type 16
VO ID : VO_0011105
NCBI Gene ID : 1489079
NCBI Protein GI : 9627105
Locus Tag : HpV16gp2
Genbank Accession : AB663783
Protein Accession : NP_041326
Taxonomy ID : 333760
Gene Starting Position : 7603
Gene Ending Position : 7899
Gene Strand (Orientation) : +
Protein Name : transforming protein E7
Protein pI : 3.97
Protein Weight : 10624.95
Protein Length : 98
Protein Note : E7 ORF from 544 to 858; putative

DNA Sequence : Show Sequence

>NC_001526.4:7603-7899 Human papillomavirus type 16, complete genome
CATGCATGGAGATACACCTACATTGCATGAATATATGTTAGATTTGCAACCAGAGACAACTGATCTCTAC
TGTTATGAGCAATTAAATGACAGCTCAGAGGAGGAGGATGAAATAGATGGTCCAGCTGGACAAGCAGAAC
CGGACAGAGCCCATTACAATATTGTAACCTTTTGTTGCAAGTGTGACTCTACGCTTCGGTTGTGCGTACA
AAGCACACACGTAGACATTCGTACTTTGGAAGACCTGTTAATGGGCACACTAGGAATTGTGTGCCCCATC
TGTTCTCAGAAACCATA

Protein Sequence : Show Sequence

>NP_041326.1 transforming protein E7 [Human papillomavirus type 16]
MHGDTPTLHEYMLDLQPETTDLYCYEQLNDSSEEEDEIDGPAGQAEPDRAHYNIVTFCCKCDSTLRLCVQ
STHVDIRTLEDLLMGTLGIVCPICSQKP

Molecule Role : Protective antigen
Molecule Role Annotation : 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).
Related Vaccine(s): ADXS11-001 , 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 Pe7(pcDNA3-Sig/sE7/LAMP) encoding E7 , Human papillomavirus E7 protein vaccine , LM1-2-E7 , MEDI0457

7. L1 HPV 16

Gene Name : L1 HPV 16
Sequence Strain (Species/Organism) : Human papillomavirus type 16
VO ID : VO_0011108
NCBI Gene ID : 1489082
NCBI Protein GI : 1046490004
Locus Tag : HpV16gp8
Genbank Accession : K02718
Protein Accession : NP_041332
3D structure: PDB ID : 2R5H
Taxonomy ID : 333760
Gene Starting Position : 4774
Gene Ending Position : 6291
Gene Strand (Orientation) : +
Protein Name : major capsid protein L1
Protein pI : 8.38
Protein Weight : 53132.12
Protein Length : 505
Protein Note : 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

DNA Sequence : Show Sequence

>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

Protein Sequence : Show Sequence

>NP_041332.2 major capsid protein L1 [Human papillomavirus type 16]
MSLWLPSEATVYLPPVPVSKVVSTDEYVARTNIYYHAGTSRLLAVGHPYFPIKKPNNNKILVPKVSGLQY
RVFRIHLPDPNKFGFPDTSFYNPDTQRLVWACVGVEVGRGQPLGVGISGHPLLNKLDDTENASAYAANAG
VDNRECISMDYKQTQLCLIGCKPPIGEHWGKGSPCTNVAVNPGDCPPLELINTVIQDGDMVDTGFGAMDF
TTLQANKSEVPLDICTSICKYPDYIKMVSEPYGDSLFFYLRREQMFVRHLFNRAGTVGENVPDDLYIKGS
GSTANLASSNYFPTPSGSMVTSDAQIFNKPYWLQRAQGHNNGICWGNQLFVTVVDTTRSTNMSLCAAIST
SETTYKNTNFKEYLRHGEEYDLQFIFQLCKITLTADVMTYIHSMNSTILEDWNFGLQPPPGGTLEDTYRF
VTSQAIACQKHTPPAPKEDPLKKYTFWEVNLKEKFSADLDQFPLGRKFLLQAGLKAKPKFTLGKRKATPT
TSSTSTTAKRKKRKL

Molecule Role : Protective antigen
Molecule Role Annotation : 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 (Nieto et al., 2009).
Related Vaccine(s): Human papillomavirus DNA vaccine pC16-L1 encoding L1 , Human papillomavirus DNA vaccine VlJns-Ll encoding L1

8. L1 HPV 52

Gene Name : L1 HPV 52
NCBI Protein GI : AAY57811.1
Genbank Accession : GQ472848
Protein Accession : ACX32362
Other Database IDs : CDD:420110
Taxonomy ID : 10618
Gene Strand (Orientation) : ?
Protein Name : L1
Protein pI : 5.31
Protein Weight : 28729.71
Protein Length : 324
Protein Note : L1 (late) protein; cl23949

Protein Sequence : Show Sequence

>AAY57811.1 L1, partial [human papillomavirus 52]
ACTGLEIGRGQPLGVGISGHPLLNKFDDTETSNKYAGKPGIDNRECLSMDYKQTQLCILGCKPPIGEHWG
KGTPCNNNSGNPGDCPPLQLINSVIQDGDMVDTGFGCMDFNTLQASKSDVPIDICSSVCKYPDYLQMASE
PYGDSLFFFLRREQMFVRHFFNRAGTLGDPVPGDLYIQGSNSGNTATVQSSAFFPTPSGSMVTSESQLFN
KPYWLQRAQGHNNGICWGNQLFVTVVDTTRSTNMTLCAEVKKESTYKNENFKEYLRHGE

Molecule Role : Protective antigen
Related Vaccine(s): 11-valent recombinant human papilloma virus vaccine (Hansenula polymorpha)

9. L2 HPV 16

Gene Name : L2 HPV 16
Sequence Strain (Species/Organism) : Human papillomavirus type 16
VO ID : VO_0011106
NCBI Gene ID : 1489081
NCBI Protein GI : 1046490003
Locus Tag : HpV16gp7
Genbank Accession : K02718
Protein Accession : NP_041331
Taxonomy ID : 333760
Gene Starting Position : 3372
Gene Ending Position : 4793
Gene Strand (Orientation) : ?
Protein Name : minor capsid protein L2
Protein pI : 6.31
Protein Weight : 47994.02
Protein Length : 473
Protein Note : L2 ORF from 4133 to 5656; putative

DNA Sequence : Show Sequence

>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

Protein Sequence : Show Sequence

>NP_041331.2 minor capsid protein L2 [Human papillomavirus type 16]
MRHKRSAKRTKRASATQLYKTCKQAGTCPPDIIPKVEGKTIADQILQYGSMGVFFGGLGIGTGSGTGGRT
GYIPLGTRPPTATDTLAPVRPPLTVDPVGPSDPSIVSLVEETSFIDAGAPTSVPSIPPDVSGFSITTSTD
TTPAILDINNTVTTVTTHNNPTFTDPSVLQPPTPAETGGHFTLSSSTISTHNYEEIPMDTFIVSTNPNTV
TSSTPIPGSRPVARLGLYSRTTQQVKVVDPAFVTTPTKLITYDNPAYEGIDVDNTLYFSSNDNSINIAPD
PDFLDIVALHRPALTSRRTGIRYSRIGNKQTLRTRSGKSIGAKVHYYYDLSTIDPAEEIELQTITPSTYT
TTSHAASPTSINNGLYDIYADDFITDTSTTPVPSVPSTSLSGYIPANTTIPFGGAYNIPLVSGPDIPINI
TDQAPSLIPIVPGSPQYTIIADAGDFYLHPSYYMLRKRRKRLPYFFSDVSLAA

Molecule Role : Protective antigen
Molecule Role Annotation : 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).
Related Vaccine(s): AAVLP(HPV16/31L2) , Human papillomavirus DNA vaccine hCRTE6E7L2 DNA encoding CRT linked to E6, E7 and L2 , Human papillomavirus L2 protein vaccine

10. L2 HPV 18

Gene Name : L2 HPV 18
Sequence Strain (Species/Organism) : Human Papillomavirus 16
NCBI Protein GI : AAP20600
Other Database IDs : CDD:165142
CDD:278914
Taxonomy ID : 333761
Protein Name : L2 protein
Protein pI : 6.32
Protein Weight : 46217.1
Protein Length : 524
Protein Note : major capsid L1 protein; Provisional

Protein Sequence : Show Sequence

>AAP20600.1 L2 protein [Human papillomavirus type 18]
MVSHRAARRKRASVTDLYKTCKQSGTCPPDVVPKVEGTTLADKILQWSSLGIFLGGLGIGTGSGTGGRTG
YIPLGGRSNTVVDVGPTRPPVVIEPVGPTDPSIVTLIEDSSVVTSGAPRPTFTGTSGFDITSAGTTTPAV
LDITPSSTSVSISTTNFTNPAFSDPSIIEVPQTGEVAGNVFVGTPTSGTHGYEEIPLQTFASSGTGEEPI
SSTPLPTVRRVAGPRLYSRAYQQVSVANPEFLTRPSSLITYDNPAFEPVDTTLTFDPRSDVPDSDFMDII
RLHRPALTSRRGTVRFSRLGQRATMFTRSGTQIGARVHFYHDISPIAPSPEYIELQPLVSATEDNDLFDI
YADDMDPAVPVPSRSTTSFAFFKYSPTISSASSYSNVTVPLTSSWDVPVYTGPDITLPSTTSVWPIVSPT
APASTQYIGIHGTHYYLWPLYYFIPKKRKRVPYFFADGFVAA

Molecule Role : Protective antigen
Molecule Role Annotation : (Pouyanfard et al., 2018)

11. L2 HPV31

Gene Name : L2 HPV31
NCBI Protein GI : ALT54672
Other Database IDs : CDD:332973
Taxonomy ID : 10585
Gene Strand (Orientation) : ?
Protein Name : L2
Protein pI : 6.29
Protein Weight : 47098.96
Protein Length : 515
Protein Note : type: 31

Protein Sequence : Show Sequence

>ALT54672.1 L2 [human papillomavirus 31]
MRSKRSTKRTKRASATQLYQTCKAAGTCPSDVIPKIEHTTIADQILRYGSMGVFFGGLGIGSGSGTGGRT
GYVPLSTRPSTVSEASIPIRPPVSIDPVGPLDPSIVSLVEESGIVDVGAPAPIPHPPTTSGFDIATTADT
TPAILDVTSVSTHENPTFTDPSVLQPPTPAETSGHLLLSSSSISTHNYEEIPMDTFIVSTNNENITSSTP
IPGVRRPARLGLYSKATQQVKVIDPTFLSAPKQLITYENPAYETVNAEESLYFSNTSHNIAPDPDFLDII
ALHRPALTSRRNTVRYSRLGNKQTLRTRSGATIGARVHYYYDISSINPAGESIEMQPLGASATTTSTLND
GLYDIYADTDFTVDTPATHNVSPSTAVQSTSAVSAYVPTNTTVPLSTGFDIPIFSGPDVPIEHAPTQVFP
FPLAPTTPQVSIFVDGGDFYLHPSYYMLKRRRKRVSYFFTDVSVAA

Molecule Role : Protective antigen
Related Vaccine(s): AAVLP(HPV16/31L2)

III. Vaccine Information

1. 11-valent recombinant human papilloma virus vaccine (Hansenula polymorpha)

a. Manufacturer:

ChinaVaccineSerum

b. Type:

Virus Like Particle

c. Status:

Clinical trial

d. Host Species for Licensed Use:

Human

e. Gene Engineering of L1 HPV 52

Type: Recombinant protein preparation
Description:
Detailed Gene Information: Click here.

f. Immunization Route

Intramuscular injection (i.m.)

g. Baboon Response

Vaccination Protocol: (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

2. AAVLP(HPV16/31L2)

a. Type:

Recombinant vector vaccine

b. Status:

Clinical trial

c. Host Species for Licensed Use:

None

d. Host Species as Laboratory Animal Model:

Rabbits and Rats

e. Antigen

Adeno-associated virus serotype 2 (AAV2) capsids

f. Gene Engineering of L2 HPV 16

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.

g. Gene Engineering of L2 HPV31

Type: Recombinant protein preparation
Description: Insertion of L2 HPV31 into VP3 at positions 583 and 453.
Detailed Gene Information: Click here.

h. Preparation

Generated AAVLPs displaying HPV16 L2 epitopes in position 587 and HPV31 L2 epitopes in position 453. (Nieto et al., 2012).

i. Immunization Route

Intramuscular injection (i.m.)

j. 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).

k. 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).

l. 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)

3. ADXS11-001

a. Product Name:

Neoadjuvant ADXS11-001 (ADXS-HPV)

b. Manufacturer:

Advaxis

c. Type:

Live, attenuated vaccine

d. Status:

Clinical trial

e. Host Species for Licensed Use:

Human

f. Antigen

(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

g. Gene Engineering of E7 Type 16

Type: Recombinant protein preparation
Description: 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).
Detailed Gene Information: Click here.

h. Vector:

(Galicia-Carmona et al., 2021)LM vector

i. Preparation

(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).

j. Immunization Route

Intravenous injection (i.v.)

k . Approved Age for Licensed Use

(Galicia-Carmona et al., 2021)18 Years and older

l. Description

(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.

4. Cervarix

a. Product Name:

Human Papillomavirus Bivalent (Types 16 and 18) Vaccine, Recombinant

b. Tradename:

Cervarix

c. Manufacturer:

GlaxoSmithKline Biologicals

d. Vaccine Ontology ID:

VO_0011559

e. CDC CVX code:

118

f. Type:

Inactivated or "killed" vaccine

g. Status:

Licensed

h. Location Licensed:

USA

i. Host Species for Licensed Use:

Human

j. Adjuvant:

VO ID: VO_0001265

k. Preparation

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).

l. Immunization Route

Intramuscular injection (i.m.)

m. Storage

Store refrigerated between 2º and 8ºC (36º and 46ºF). Do not freeze.

n . Approved Age for Licensed Use

Females ages 10 to 25

5. Gardasil

a. Product Name:

Human Papillomavirus Quadrivalent (Types 6, 11, 16, 18) Vaccine, Recombinant

b. Tradename:

Gardasil

c. Manufacturer:

Merck & Co., Inc.

d. Vaccine Ontology ID:

VO_0000049

e. CDC CVX code:

f. Type:

Subunit vaccine

g. Status:

Licensed

h. Location Licensed:

USA (License #0002)

i. Host Species for Licensed Use:

Human

j. Antigen

Virus-like particles (VLPs) of the major capsid (L1) protein of HPV Types 6, 11, 16, and 18.

k. Adjuvant:

VO ID: VO_0001323

l. Preparation

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).

m. Immunization Route

Intramuscular injection (i.m.)

n. Storage

GARDASIL should be refrigerated at 2 to 8 degrees Celcius. Do not freeze. Protect from light.

o . Approved Age for Licensed Use

Females ages 9-26

p. Contraindication

Hypersensitivity, including severe allergic reactions to yeast (a vaccine component), or after a previous dose of GARDASIL.

q. Description

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).

r. Human Response

Vaccination Protocol: 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).
Immune Response: 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).
Side Effects: Most common side effect of immunization was headache. Other side effects include: fever, nausea, dizziness, injection site pain and swelling.

6. Gardasil 9

a. Product Name:

Human Papillomavirus 9-valent Vaccine, Recombinant

b. Tradename:

Gardasil 9

c. Manufacturer:

Merck & Co., Inc.

d. CDC CVX code:

165

e. Type:

Subunit vaccine

f. Status:

Licensed

g. Location Licensed:

USA, Canada

h. Host Species for Licensed Use:

Human

i. Allergen:

Yeast

j. Immunization Route

Intramuscular injection (i.m.)

k . Approved Age for Licensed Use

9-26 years

l. Description

9-valent derivative of Gardasil

7. Human papillomavirus DNA vaccine CRT/E7 DNA

a. Vaccine Ontology ID:

VO_0004331

b. Type:

DNA vaccine

c. Status:

Research

d. Host Species as Laboratory Animal Model:

Mouse

e. Gene Engineering of E7 Type 16

Type: DNA vaccine construction
Description: Vector pCDNA3 expressed E7 protein of HPV 16 and 18 (Cheng et al., 2001).
Detailed Gene Information: Click here.

f. Vector:

pCDNA3 (Cheng et al., 2001)

g. Immunization Route

Intramuscular injection (i.m.)

h. 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).

8. Human papillomavirus DNA vaccine E7IR

a. Vaccine Ontology ID:

VO_0004332

b. Type:

DNA vaccine

c. Status:

Research

d. Host Species as Laboratory Animal Model:

Mouse

e. Gene Engineering of E7 Type 16

Type: DNA vaccine construction
Description: Vector APL023expressed the E7 gene (Brinkman et al., 2007).
Detailed Gene Information: Click here.

f. Vector:

APL023 (Brinkman et al., 2007)

g. Immunization Route

Gene gun

h. 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).

9. Human papillomavirus DNA vaccine E7SH DNA

a. Vaccine Ontology ID:

VO_0004333

b. Type:

DNA vaccine

c. Status:

Research

d. Host Species as Laboratory Animal Model:

Mouse

e. Gene Engineering of E7 Type 16

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.

f. Vector:

pCDNA3 (Osen et al., 2001)

g. Immunization Route

Intramuscular injection (i.m.)

h. 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).

10. Human papillomavirus DNA vaccine hCRTE6E7L2 DNA encoding CRT linked to E6, E7 and L2

a. Vaccine Ontology ID:

VO_0004475

b. Type:

DNA vaccine

c. Status:

Research

d. Host Species as Laboratory Animal Model:

Mouse

e. Gene Engineering of E6 Type 16

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.

f. Gene Engineering of E7 Type 16

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.

g. Gene Engineering of L2 HPV 16

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.

h. Gene Engineering of CRTC

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.

i. Vector:

pNGVL4a vector (National Gene Vector lab) (Kim et al., 2008)

j. Immunization Route

Gene gun

k. 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).

11. Human papillomavirus DNA vaccine pC16-L1 encoding L1

a. Vaccine Ontology ID:

VO_0004330

b. Type:

DNA vaccine

c. Status:

Research

d. Gene Engineering of L1 HPV 16

Type: DNA vaccine construction
Description: Vector pCDNA3 expressed L1 (Rocha-Zavaleta et al., 2002).
Detailed Gene Information: Click here.

e. Vector:

pCDNA3 (Rocha-Zavaleta et al., 2002)

f. Immunization Route

Intramuscular injection (i.m.)

g. 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).

12. Human papillomavirus DNA vaccine Pe7(pcDNA3-Sig/sE7/LAMP) encoding E7

a. Vaccine Ontology ID:

VO_0004329

b. Type:

DNA vaccine

c. Status:

Research

d. Host Species as Laboratory Animal Model:

Mouse

e. Gene Engineering of E7 Type 16

Type: DNA vaccine construction
Description: Vector pcDNA3 expressed HPV oncogenic proteins E7 (Sin, 2009).
Detailed Gene Information: Click here.

f. Vector:

pcDNA3 (Sin, 2009)

g. Immunization Route

Intramuscular injection (i.m.)

h. 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).

13. Human papillomavirus DNA vaccine pNGVL4a-E6/opt

a. Vaccine Ontology ID:

VO_0011480

b. Type:

DNA vaccine

c. Status:

Research

d. Antigen

Human papillomavirus E6

e. Gene Engineering of E6 Type 16

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.

f. Vector:

pNGVL4a

g. Immunization Route

Intradermal injection (i.d.)

h. 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 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).
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).

14. Human papillomavirus DNA vaccine VlJns-Ll encoding L1

a. Vaccine Ontology ID:

VO_0004328

b. Type:

DNA vaccine

c. Status:

Research

d. Host Species as Laboratory Animal Model:

Rabbit

e. Gene Engineering of L1 HPV 16

Type: DNA vaccine construction
Description: Vector VlJns expressed the major viral capsid protein L1 (Donnelly et al., 1996).
Detailed Gene Information: Click here.

f. Vector:

VlJns (Donnelly et al., 1996)

g. Immunization Route

Intramuscular injection (i.m.)

h. Rabbit Response

Vaccine Immune Response Type: VO_0000286
Efficacy: 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).

15. Human papillomavirus E7 protein vaccine

a. Vaccine Ontology ID:

VO_0011395

b. Type:

Subunit vaccine

c. Status:

Research

d. Antigen

Human papillomavirus E7

e. Gene Engineering of E7 Type 16

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.

f. Adjuvant:

VO ID: VO_0000142

g. Immunization Route

Subcutaneous injection

h. 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 × 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).
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).

16. Human papillomavirus L2 protein vaccine

a. Vaccine Ontology ID:

VO_0011397

b. Type:

Subunit vaccine

c. Status:

Research

d. Antigen

Human papillomavirus L2

e. Gene Engineering of L2 HPV 16

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.

f. Adjuvant:

VO ID: VO_0000884
Description: GPI-0100 adjuvant or alum (Jagu et al., 2009)

g. Immunization Route

Subcutaneous injection

h. 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 × 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).
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).

17. LM1-2-E7

a. Vaccine Ontology ID:

VO_0004803

b. Type:

Recombinant vector vaccine

c. Status:

Research

d. Host Species for Licensed Use:

Baboon

e. Gene Engineering of E7 Type 16

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.

f. Preparation

The E7 fragment was amplified with PCR then cloned into the chromosome of L. monocytogenes (Jia et al., 2012).

g. Immunization Route

Intramuscular injection (i.m.)

h. 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).

18. MEDI0457

a. Product Name:

MEDI 0457

b. Manufacturer:

CELLECTRA (Inovio Pharmaceuticals, San Diego, CA)

c. Type:

DNA vaccine

d. Status:

Clinical trial

e. Host Species for Licensed Use:

Human

f. Antigen

(Hasan et al., 2020)E6 and E7 serve as non self antigens

g. Gene Engineering of E6 HPV 18

Type: DNA vaccine construction
Description: E6 gene is inserted into a DNA vaccine plasmid, which allows the expression of the E6 protein.
Detailed Gene Information: Click here.

h. Gene Engineering of E7 Type 16

Type: Recombinant protein preparation
Description: The E7 gene is inserted into a DNA vaccine plasmid, which allows the expression of the E7 protein.
Detailed Gene Information: Click here.

i. Immunization Route

Intramuscular injection (i.m.)

j. Description

(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

19. V503

a. Product Name:

Human Papillomavirus 9vHPV (6,11,16,18,31,33,45,52,58) Nonvalent Vaccine, Recombinant

b. Tradename:

Gardasil

c. Manufacturer:

Merck Sharp & Dohme LLC

d. Type:

Recombinant vector vaccine

e. Status:

Licensed

f. Location Licensed:

USA

g. Host Species for Licensed Use:

Human

h. Immunization Route

Intramuscular injection (i.m.)

i . Approved Age for Licensed Use

Females: 16-26 yrs Males:9-15 yrs

j. Description

Instead of a 4VHPV, this vaccine is a 9 valent HPV vaccine providing more protection.

k. Human Response

Vaccination Protocol: Participants (n = 600) were randomized to receive 9vHPV or qHPV vaccines on day 1, month 2 and month 6.
Description: 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).

IV. References

1. 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].

2. Chatterjee, 2014: Chatterjee A. The next generation of HPV vaccines: nonavalent vaccine V503 on the horizon. Expert review of vaccines. 2014; 13(11); 1279-1290. [PubMed: 25256262].

3. 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].

4. Chu et al., 2011: Phase I of Human Papillomavirus (HPV) DNA Plasmid (VGX-3100) + Electroporation for CIN 2 or 3 [http://www.clinicaltrials.gov/ct2/show/NCT00685412?term=vgx&rank=1]

5. Donnelly et al., 1996: Donnelly JJ, Martinez D, Jansen KU, Ellis RW, Montgomery DL, Liu MA. Protection against papillomavirus with a polynucleotide vaccine. The Journal of infectious diseases. 1996; 173(2); 314-320. [PubMed: 8568291].

6. FDA: Cevarix: FDA: Cervarix [http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm186957.htm]

7. FDA: Gardasil: FDA: Gardasil information [http://www.fda.gov/Cber/products/gardasil.htm]

8. Galicia-Carmona et al., 2021: Galicia-Carmona T, Arango-Bravo E, Serrano-Olvera JA, Flores-de La Torre C, Cruz-Esquivel I, Villalobos-Valencia R, Morán-Mendoza A, Castro-Eguiluz D, Cetina-Pérez L. ADXS11-001 LM-LLO as specific immunotherapy in cervical cancer. Human vaccines & immunotherapeutics. 2021; 17(8); 2617-2625. [PubMed: 33793380].

9. Hasan et al., 2020: Hasan Y, Furtado L, Tergas A, Lee N, Brooks R, McCall A, Golden D, Jolly S, Fleming G, Morrow M, Kraynyak K, Sylvester A, Arif F, Levin M, Schwartz D, Boyer J, Skolnik J, Esser M, Kumar R, Bagarazzi M, Weichselbaum R, Spiotto M. A Phase 1 Trial Assessing the Safety and Tolerability of a Therapeutic DNA Vaccination Against HPV16 and HPV18 E6/E7 Oncogenes After Chemoradiation for Cervical Cancer. International journal of radiation oncology, biology, physics. 2020; 107(3); 487-498. [PubMed: 32151670].

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