Human papilloma virus (HPV) widely infects humans and can cause cervical cancer and other malignant tumors, seriously endangering human health. In 2006, Merck launched the first HPV vaccine, making cervical cancer and condyloma caused by HPV preventable. Glaxosmithkline's Cervarix, Merck's Gardasil and Gardasil 9 are on the market. The HPV vaccine is effective in preventing HPV infection and the disease it causes, and the World Health Organization (WHO) is implementing a global plan to eliminate cervical cancer. However, how to evaluate vaccines scientifically, especially their clinical immunogenicity, is very important.
The natural and adaptive immunity of the body's immune system controls and removes infected HPV, so most infections are self-limiting. Studies have shown that more than 90% of infected people will clear the virus within 3 years1. However, HPV has multiple mechanisms to escape the immune system so that a small number of people remain infected.
HPV infection will produce antibodies against L1, L2 and E6 and other proteins, among which L1 antibodies account for the largest proportion, but mostly type specific antibodies, it is difficult to produce type cross immune protection. The antibody molecular types of HPV are mainly IgG and IgA, among which IgA is divided into serum type and secreting type. In the early stage, IgA was thought to be more useful in mucous membrane than IgG. However, later clinical trials proved that IgG plays a major role in anti-HPV infection2-3. L2 plays an important role in HPV immune escape, mainly by preventing the increase of immune-related signal molecules on the surface of Langerhans cells and inhibiting their ability to activate T cells4. In addition, certain types of E6 and E7 can down-regulate type I IFN expression by interfering with cell cycle5.
The immune response caused by natural infection is weak and it is difficult to produce antibodies with enough titer to neutralize the invading virus. Inoculation of preventive vaccine can stimulate the body to produce a high titer of neutralizing antibodies, clear the invasion of the virus. Clinical results show that neutralizing antibodies produced by HPV vaccine can penetrate into the blood vessel wall to reach the infection site and bind the virus to make it lose the ability to infect cells6. Both L1 and L2 are good candidate proteins for preventive vaccine.
Gardasil®4, developed by Merck in the United States in 2006, was the first HPV vaccine to be marketed in the world. The vaccine contains HPV 6, 11, 16 and 18 strains expressed by Saccharomyces cerevisiae. Vaccines made by adsorption to AAHS can prevent about 90% of condyloma acuminatum and about 70% of cervical cancer.
Cervarix®, developed by GlaxoSmithKline (GSK) of the UK, was approved by the European Union in September 2007 and the US FDA in October 2009. The vaccine, which contains baculovirus-insect cells expressing HPV 16 and 18 VLP components, does not contain low-risk HPV and therefore does not protect against condyloma acuminatum, but it also protects about 70 percent of cervical and uterine cancers. The vaccine uses AS04, an adjuvant developed by GSK.
Gardasil®9, developed by Merck, was approved in the United States in December 2014. The vaccine, also expressed in Saccharomyces cerevisiae, contains nine VLP components of HPV 6, 11, 16, 18, 31, 33, 45, 52 and 58, and can prevent approximately 90% of cervical, vaginal, vulvar and anal cancers caused by seven high-risk HPV types, and approximately 90% of condyloma acuminatum caused by low-risk HPV 6 and 11.
Fig. 1 Three main types of assays or immunogenicity evaluation12
Merck's competitive immunoassay Luminex (cLIA) detects antibodies in serum samples that compete with specific neutralizing monoclonal antibodies7-8. CLIA detects type specific neutralizing monoclonal antibodies and conformation intact VLP that need to be labeled. Antibodies in serum bind to VLP and inhibit the binding of labeled monoclonal antibodies, thus reducing the signal value of detection. By labeling different types of specific monoclonal antibodies and combining Luminex detection, the synchronous detection of different types of antibodies can be realized, thus improving the detection flux of the method. This method was used to evaluate the clinical immunogenicity of Gardasil® and Gardasil®9 of Merck.
cLIA can detect all classes of antibodies (IgG, IgM, IgA, etc.), but only for a single epitope. Therefore, the method has good specificity, but may underestimate the level of functional antibodies in the sample.
The assay can detect VLP-bound IgG in samples, and other types of antibodies, such as IgA or different IgG subclasses, can also be detected by altering the secondary antibody. This method can recognize both conformational epitopes and non-conformational epitopes, and the detected antibodies include both neutralizing and non-neutralizing antibodies.
The neutralization test is considered the “gold standard” for detecting protective antibodies and is recommended by the WHO as a reference method for evaluating vaccine-induced protective antibodies. PBNA can detect all neutralizing antibodies (such as IgM, IgA, IgG) in vitro9.
Neutralization test is a detection method based on cell culture. Compared with binding test, the original method has a higher degree of variation, and the operation is relatively cumbersome, which makes it difficult to conduct high-throughput detection. With the development of detection methods, the detection flux of neutralizing antibody detection method is also gradually improving, especially the 384 well plate automatic detection method based on Gluc10 and the three-color pseudovirus binding immune spot counting method11, which greatly improves the detection flux while reducing the sample dosage. It lays a foundation for the application of this method in clinical trials.
Creative Diagnostics has launched the most complete HPV L1 antibody products, covering HPV 6/11/16/18/31/33/45/52/58, including polyclonal, monoclonal antibody and monoclonal antibody screening set, mainly used for ELISA, Western Blot, neutralization and in vitro vaccine in vitro efficacy testing. View More
|Monoclonal antibody set||Clone number-IC50 (μg/ml) for Neut:|
|Anti-HPV 6 L1 monoclonal antibody (set)||1E5-0.0092, 39G7-0.0085, 39G2-0.00081, 42G5-0.00076, 44B11-0.00008, 43C7-0.0033|
|Anti-HPV 11 L1 monoclonal antibody (set)||34C9-4.27, 35C1-15.87, 35H5-743, 34E5-43|
|Anti-HPV 16 L1 monoclonal antibody (set)||2A1-0.00033, 3D5-0.0021, 4G12-0.0020, 5A6-0.0024, 6C7-0.0020, 7B9-0.00027|
|Anti-HPV 18 L1 monoclonal antibody (set)||1B1-97, 3A2-0.00030, 3A4-1.46, 4H1-0.76, 4H5-1.31, 7H8-0.0025|
|Anti-HPV 31 L1 monoclonal antibody (set)||19C2-0.0061, 19B6-0.12|
|Anti-HPV 33 L1 monoclonal antibody (set)||4C2, 4F1, 4G4, 4H4, 6C11, 6D2|
|Anti-HPV 45 L1 monoclonal antibody (set)||30H6-0.54, 35B12-1.70, 35H9-0.49, 40H1-0.15, 46G5-0.028, 48B1-0.14|
|Anti-HPV 52 L1 monoclonal antibody (set)||36B9-0.00056, 36E12-0.00061, 40C2-0.0035, 41C3-0.0011, 41D1-0.00015, 42A2-0.00040|
|Anti-HPV 58 L1 monoclonal antibody (set)||1D2-0.015, 2E11-0.021, 2F11-0.014, 2F7-0.020, 2F9-0.10, 2G7-0.015|
*The antibodies are provided as screening sets (6 different clones per set), each clone is also available separately.
|Polyclonal antibody||HRP conjugated|
|Anti-HPV6 L1 polyclonal antibody||Anti-HPV6 L1 polyclonal antibody [HRP]|
|Anti-HPV11 L1 polyclonal antibody||Anti-HPV11 L1 polyclonal antibody [HRP]|
|Anti-HPV16 L1 polyclonal antibody||Anti-HPV16 L1 polyclonal antibody [HRP]|
|Anti-HPV18 L1 polyclonal antibody||Anti-HPV18 L1 polyclonal antibody [HRP]|
|Anti-HPV31 L1 polyclonal antibody||Anti-HPV31 L1 polyclonal antibody [HRP]|
|Anti-HPV33 L1 polyclonal antibody||Anti-HPV33 L1 polyclonal antibody [HRP]|
|Anti-HPV45 L1 polyclonal antibody||Anti-HPV45 L1 polyclonal antibody [HRP]|
|Anti-HPV52 L1 polyclonal antibody||Anti-HPV52 L1 polyclonal antibody [HRP]|
|Anti-HPV58 L1 polyclonal antibody||Anti-HPV58 L1 polyclonal antibody [HRP]|
|Anti-HPV 35-L1 Polyclonal antibody|
|Anti-HPV 39-L1 Polyclonal antibody|
|Anti-HPV 31-L1 Polyclonal antibody|
|Anti-HPV 59-L1 Polyclonal antibody|
|Anti-HPV 68-L1 Polyclonal antibody|
Creative Diagnostics has established a global-leading virus-like particles (VLPs) manufacture platform using E. coli cell system. With years of exploration, our scientists have successfully obtained various highly purified HPV VLPs. Our products have significantly contributed to the HPV vaccine related research. View More
|Catalog#||Product Description||Expression System||Application|
|DAGF-227||Recombinant HPV type 6 L1 protein (VLP)||E. Coli||ELISA, Antibody Detection|
|DAGF-228||Recombinant HPV type 11 L1 protein (VLP)||E. Coli||ELISA, Antibody Detection|
|DAGF-229||Recombinant HPV type 16 L1 protein (VLP)||E. Coli||ELISA, Antibody Detection|
|DAGF-230||Recombinant HPV type 18 L1 protein (VLP)||E. Coli||ELISA, Antibody Detection|
|DAGF-231||Recombinant HPV type 31 L1 protein (VLP)||E. Coli||ELISA, Antibody Detection|
|DAGF-232||Recombinant HPV type 33 L1 protein (VLP)||E. Coli||ELISA, Antibody Detection|
|DAGF-233||Recombinant HPV type 45 L1 protein (VLP)||E. Coli||ELISA, Antibody Detection|
|DAGF-234||Recombinant HPV type 52 L1 protein (VLP)||E. Coli||ELISA, Antibody Detection|
|DAGF-235||Recombinant HPV type 58 L1 protein (VLP)||E. Coli||ELISA, Antibody Detection|
|DAGC142||Recombinant HPV type 35 L1 protein (VLP)||E. Coli||ELISA, Antibody Detection|
|DAGC143||Recombinant HPV type 39 L1 protein (VLP)||E. Coli||ELISA, Antibody Detection|
|DAGC144||Recombinant HPV type 51 L1 protein (VLP)||E. Coli||ELISA, Antibody Detection|
|DAGC145||Recombinant HPV type 56 L1 protein (VLP)||E. Coli||ELISA, Antibody Detection|
|DAGC146||Recombinant HPV type 59 L1 protein (VLP)||E. Coli||ELISA, Antibody Detection|
|DAGC147||Recombinant HPV type 68 L1 protein (VLP)||E. Coli||ELISA, Antibody Detection|
The CD Pseudotyped GFP HPV production is based on the transfection of a 293 cell line, 293FT, engineered to express high levels of SV40 large T antigen. The cells are co-transfected with codon-modified papillomavirus capsid genes, L1 and L2, together with a pseudogenome plasmid containing the SV40 origin of replication. Pseudovirus (PsV) encapsidating a GFP reporter plasmid can be used to develop a high-throughput in vitro neutralization assay in a 96-well plate format. View More
|Cat. No.||Product Name||Reporter||Cell Line|
|PSVG-HPV6||Pseudotyped GFP HPV6||GFP||HEK293 FT|
|PSVG-HPV11||Pseudotyped GFP HPV11||GFP||HEK293 FT|
|PSVG-HPV16||Pseudotyped GFP HPV16||GFP||HEK293 FT|
|PSVG-HPV18||Pseudotyped GFP HPV18||GFP||HEK293 FT|
|PSVG-HPV31||Pseudotyped GFP HPV31||GFP||HEK293 FT|
|PSVG-HPV33||Pseudotyped GFP HPV33||GFP||HEK293 FT|
|PSVG-HPV35||Pseudotyped GFP HPV35||GFP||HEK293 FT|
|PSVG-HPV39||Pseudotyped GFP HPV39||GFP||HEK293 FT|
|PSVG-HPV45||Pseudotyped GFP HPV45||GFP||HEK293 FT|
|PSVG-HPV51||Pseudotyped GFP HPV51||GFP||HEK293 FT|
|PSVG-HPV52||Pseudotyped GFP HPV52||GFP||HEK293 FT|
|PSVG-HPV56||Pseudotyped GFP HPV56||GFP||HEK293 FT|
|PSVG-HPV58||Pseudotyped GFP HPV58||GFP||HEK293 FT|
|PSVG-HPV59||Pseudotyped GFP HPV59||GFP||HEK293 FT|
|PSVG-HPV68||Pseudotyped GFP HPV68||GFP||HEK293 FT|