Cervarix
Encyclopedia
Cervarix is a vaccine
against certain types of cancer-causing human papillomavirus
(HPV).
Cervarix is designed to prevent infection from HPV types 16 and 18, that cause about 70% of cervical cancer
cases. These types also cause some other genital cancers and some oropharyngeal cancers. Additionally, some cross-reactive protection against virus strains 45 and 31 were shown in clinical trials. Cervarix also contains AS04
, a proprietary adjuvant
that has been found to boost the immune system
response for a longer period of time.
Cervarix is manufactured by GlaxoSmithKline
. An alternative product, from Merck & Co.
, is known as Gardasil
.
Medical Center, the University of Rochester
, the University of Queensland
in Australia, and the U.S. National Cancer Institute
.
and Brazil
showed 100% protection against type 16 and type 18 HPV. Phase III trials, including over 18,000 women from 14 countries in Pacific Asia, Europe
, Latin America
and North America
.
As of 2009 the manufacturer was conducting a trial to compare the immunogenicity and safety of Cervarix with Gardasil
. Subsequent studies showed Cervarix generated higher antibody levels than Gardasil, the other commercally available HPV vaccine, upon testing seven months later, with twice the level for HPV type 16 and six times for HPV type 18. In addition Cervarix induced twice as many memory B cells as Gardasil for both these HPV strains.
Cervarix is indicated for the prevention of the following diseases caused by oncogenic HPV types 16 and 18: cervical cancer, cervical intraepithelial neoplasia
(CIN) grade 2 or worse and adenocarcinoma in situ, and CIN grade 1. Cervarix is approved for use in females 10 through 25 years of age.
In common with some other prefilled syringe vaccination products, the tip cap and the rubber plunger of the needleless prefilled syringes contain dry natural latex rubber that may cause allergic reactions in latex sensitive individuals
. The vial stopper does not contain latex.
. L1 protein is in the form of non-infectious virus-like particles (VLPs) produced by recombinant DNA technology using a Baculovirus expression system which uses Hi-5 Rix4446 cells derived from the insect Trichoplusia ni. The vaccine contains no live virus and no DNA, so it cannot infect the patient.
In the UK
it is included in the national vaccination programme for teenage and pre-teenage girls aged 12–13 and 17–18. This caused some controversy since Cervarix was chosen over Gardasil
, even though Gardasil protects against additional HPV types 6 and 11 (which cause genital warts). However, the efficacy of Cervarix is higher
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...
against certain types of cancer-causing human papillomavirus
Human papillomavirus
Human papillomavirus is a member of the papillomavirus family of viruses that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes...
(HPV).
Cervarix is designed to prevent infection from HPV types 16 and 18, that cause about 70% of cervical cancer
Cervical cancer
Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. One of the most common symptoms is abnormal vaginal bleeding, but in some cases there may be no obvious symptoms until the cancer is in its advanced stages...
cases. These types also cause some other genital cancers and some oropharyngeal cancers. Additionally, some cross-reactive protection against virus strains 45 and 31 were shown in clinical trials. Cervarix also contains AS04
AS04
AS04 is a trade name for combination of adjuvants used in various vaccine product by GlaxoSmithKline , in particular the Cervarix HPV vaccine. It consists of aluminum hydroxide and monophosphoryl lipid A . Furthermore it is the successor of AS03 which is a Squalene based adjuvant.-External links:***...
, a proprietary adjuvant
Immunologic adjuvant
In immunology, an adjuvant is an agent that may stimulate the immune system and increase the response to a vaccine, without having any specific antigenic effect in itself. The word “adjuvant” comes from the Latin word adiuvare, meaning to help or aid...
that has been found to boost the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
response for a longer period of time.
Cervarix is manufactured by GlaxoSmithKline
GlaxoSmithKline
GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...
. An alternative product, from Merck & Co.
Merck & Co.
Merck & Co., Inc. , also known as Merck Sharp & Dohme or MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. The Merck headquarters is located in Whitehouse Station, New Jersey, an unincorporated area in Readington Township...
, is known as Gardasil
Gardasil
Gardasil , also known as Gardisil or Silgard, is a vaccine for use in the prevention of certain types of human papillomavirus , specifically HPV types 6, 11, 16 and 18. HPV types 16 and 18 cause an estimated 70% of cervical cancers, and are responsible for most HPV-induced anal, vulvar, vaginal,...
.
History
The vaccine was developed, in parallel, by researchers at Georgetown UniversityGeorgetown University
Georgetown University is a private, Jesuit, research university whose main campus is in the Georgetown neighborhood of Washington, D.C. Founded in 1789, it is the oldest Catholic university in the United States...
Medical Center, the University of Rochester
University of Rochester
The University of Rochester is a private, nonsectarian, research university in Rochester, New York, United States. The university grants undergraduate and graduate degrees, including doctoral and professional degrees. The university has six schools and various interdisciplinary programs.The...
, the University of Queensland
University of Queensland
The University of Queensland, also known as UQ, is a public university located in state of Queensland, Australia. Founded in 1909, it is the oldest and largest university in Queensland and the fifth oldest in the nation...
in Australia, and the U.S. National Cancer Institute
National Cancer Institute
The National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
.
Clinical Trials
Phase II trials including 1,100 women from North AmericaNorth America
North America is a continent wholly within the Northern Hemisphere and almost wholly within the Western Hemisphere. It is also considered a northern subcontinent of the Americas...
and Brazil
Brazil
Brazil , officially the Federative Republic of Brazil , is the largest country in South America. It is the world's fifth largest country, both by geographical area and by population with over 192 million people...
showed 100% protection against type 16 and type 18 HPV. Phase III trials, including over 18,000 women from 14 countries in Pacific Asia, Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
, Latin America
Latin America
Latin America is a region of the Americas where Romance languages – particularly Spanish and Portuguese, and variably French – are primarily spoken. Latin America has an area of approximately 21,069,500 km² , almost 3.9% of the Earth's surface or 14.1% of its land surface area...
and North America
North America
North America is a continent wholly within the Northern Hemisphere and almost wholly within the Western Hemisphere. It is also considered a northern subcontinent of the Americas...
.
As of 2009 the manufacturer was conducting a trial to compare the immunogenicity and safety of Cervarix with Gardasil
Gardasil
Gardasil , also known as Gardisil or Silgard, is a vaccine for use in the prevention of certain types of human papillomavirus , specifically HPV types 6, 11, 16 and 18. HPV types 16 and 18 cause an estimated 70% of cervical cancers, and are responsible for most HPV-induced anal, vulvar, vaginal,...
. Subsequent studies showed Cervarix generated higher antibody levels than Gardasil, the other commercally available HPV vaccine, upon testing seven months later, with twice the level for HPV type 16 and six times for HPV type 18. In addition Cervarix induced twice as many memory B cells as Gardasil for both these HPV strains.
Indications
HPV is a virus, usually transmitted sexually, which can cause cervical cancer in a small percentage of those women genital infected. Cervarix is a preventative HPV vaccine, not therapeutic. HPV immunity is type-specific, so a successful series of Cervarix shots will not block infection from cervical cancer-causing HPV types other than HPV types 16 and 18 and some related types, so experts continue to recommend routine cervical Pap smears even for women who have been vaccinated. Vaccination alone, without continued screening, would prevent fewer cervical cancers than regular screening alone.Cervarix is indicated for the prevention of the following diseases caused by oncogenic HPV types 16 and 18: cervical cancer, cervical intraepithelial neoplasia
Cervical intraepithelial neoplasia
Cervical intraepithelial neoplasia , also known as cervical dysplasia and cervical interstitial neoplasia, is the potentially premalignant transformation and abnormal growth of squamous cells on the surface of the cervix. CIN is not cancer, and is usually curable...
(CIN) grade 2 or worse and adenocarcinoma in situ, and CIN grade 1. Cervarix is approved for use in females 10 through 25 years of age.
Administration
Immunization with Cervarix consists of 3 doses of 0.5-mL each, by intramuscular injection according to the following schedule: 0, 1, and 6 months. The preferred site of administration is the deltoid region of the upper arm. Cervarix is available in 0.5-mL single-dose vials and prefilled TIP-LOK syringes.Limitations of effectiveness
Cervarix does not provide protection against disease due to all HPV types, nor against disease if a woman has previously been exposed through sexual activity and protection may not be obtained by all recipients. It is therefore recommended that women continue to adhere to cervical cancer screening procedures.Adverse effects
- The most common local adverse reactions and general adverse events in ≥20% of patients were pain, redness, and swelling at the injection site, fatigue, headache, muscle pain (myalgiaMyalgiaMyalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
), gastrointestinal symptoms, and joint pain (arthralgiaArthralgiaArthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication....
). - The most common general adverse events in ≥20% of subjects were fatigue, headache, muscle pain (myalgiaMyalgiaMyalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
), gastrointestinal symptoms, and joint pain (arthralgiaArthralgiaArthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication....
).
In common with some other prefilled syringe vaccination products, the tip cap and the rubber plunger of the needleless prefilled syringes contain dry natural latex rubber that may cause allergic reactions in latex sensitive individuals
Latex allergy
Latex allergy is a medical term encompassing a range of allergic reactions to natural rubber latex.-Type I:The most serious and rare form, type I is an immediate and potentially life-threatening reaction, not unlike the severe reaction some people have to bee stings...
. The vial stopper does not contain latex.
Ingredients
The active components of the vaccine are:- Human Papillomavirus type 16 L1 protein 20 micrograms
- Human Papillomavirus type 18 L1 protein 20 micrograms
- AS04AS04AS04 is a trade name for combination of adjuvants used in various vaccine product by GlaxoSmithKline , in particular the Cervarix HPV vaccine. It consists of aluminum hydroxide and monophosphoryl lipid A . Furthermore it is the successor of AS03 which is a Squalene based adjuvant.-External links:***...
adjuvant, containing: 3-O-desacyl-4'- monophosphoryl lipid A (MPL) 50 micrograms adsorbed on aluminium hydroxideAluminium hydroxideAluminium hydroxide, Al3, ATH, sometimes erroneously called Hydrate of alumina, is found in nature as the mineral gibbsite and its three, much more rare forms, polymorphs: bayerite, doyleite and nordstrandite. Closely related are aluminium oxide hydroxide, AlO, and aluminium oxide, Al2O3,...
, hydrated (Al(OH)3) 0.5 milligrams Al 3+ in total
Biotechnology
Cervarix is created using the L1 protein of the viral capsidCapsid
A capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...
. L1 protein is in the form of non-infectious virus-like particles (VLPs) produced by recombinant DNA technology using a Baculovirus expression system which uses Hi-5 Rix4446 cells derived from the insect Trichoplusia ni. The vaccine contains no live virus and no DNA, so it cannot infect the patient.
Licensing
- Australia - Cervarix received approval in May 2007 in Australia for women ages 10 to 45.
- Philippines - On August 25, 2007 GlaxoSmithKline launched Cervarix in the Philippines after approval by the local Bureau of Food and Drugs.
- European Union - Cervarix was approved in September 2007 in the European Union.
- United States of America - The FDA approved Cervarix on 16 October 2009.
- On March 29, 2007 GlaxoSmithKline submitted a Biologic License ApplicationBiologic License ApplicationAs defined by the US FDA, a Biologic License Application is: Biological products are approved for marketing under the provisions of the Public Health Service Act. The Act requires a firm who manufactures a biologic for sale in interstate commerce to hold a license for the product...
(BLA) for Cervarix (human papillomavirus vaccine, AS04 adjuvant-adsorbed), to the U.S. Food and Drug Administration (FDA) which included data from clinical trials in almost 30,000 females 10 to 55 years of age and contains data from the largest Phase III cervical cancer vaccine efficacy trial to that date. - GSK had awaited results of further trials to submit to the FDA. Approval had not been expected before late 2009.
- On March 29, 2007 GlaxoSmithKline submitted a Biologic License Application
In the UK
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
it is included in the national vaccination programme for teenage and pre-teenage girls aged 12–13 and 17–18. This caused some controversy since Cervarix was chosen over Gardasil
Gardasil
Gardasil , also known as Gardisil or Silgard, is a vaccine for use in the prevention of certain types of human papillomavirus , specifically HPV types 6, 11, 16 and 18. HPV types 16 and 18 cause an estimated 70% of cervical cancers, and are responsible for most HPV-induced anal, vulvar, vaginal,...
, even though Gardasil protects against additional HPV types 6 and 11 (which cause genital warts). However, the efficacy of Cervarix is higher
External links
- cervicalcancer.gsk.com official global GSK portal for cervical cancer vaccine information
- Cervarix GSK UK Cervarix official site
- Cervarix GSK presentation
- "Human Papillomavirus (HPV) Vaccines", National Cancer InstituteNational Cancer InstituteThe National Cancer Institute is part of the National Institutes of Health , which is one of 11 agencies that are part of the U.S. Department of Health and Human Services. The NCI coordinates the U.S...
Fact Sheet, US National Institutes of Health, October 22, 2009.