2. Human Pappiloma Virus DsDNA, Circular genome
Associated with cervical , anal, vaginal,, subset of head and neck cancer
High risk HPV
Low Risk HPV

3. High risk type- Cervical cancer
HPV 16, 18, 31 & 45
Causal agents of 80% of cervical cancer
2nd most cancer in women with 493,243 new cases worldwide, 230,000 deaths every year
Prevalence: Europe, North America, and Australia (74 to 77%)
Africa, Asia, and South/Central America (65 to 70%)

4. How cervical cancer develops

5. The life cycle of HPV

6. How to prevent HPV Prophylactic and Therapeutic vaccine
Specific for high risk type
Difference between Prophylactic and therapeutic vaccine

7. Prophylactic vaccines
Polyvalent VLP prophylactic vaccine***
Live vaccine vectors
L2 based vaccine

8. Polyvalent VLP prophylactic vaccine (Commercially available vaccines)
CERVARIX & GARDASIL
Two pharmaceutical companies: GlaxoSmithKline (GSK) and Merck
GSK Vaccine-CERVARIX-targets-HPV16, HPV18
FDA Approved for yrs age women
Merck Vaccine-GARDASIL- targets- HPV 6, 11, 16, 18
FDA approved for 9-26 yrs age men and women

10. Therapeutic vaccines Targets the early proteins For e.g DNA Vaccines
 MEL-1, created by Dr. Ricardo Rosales.

11. HISTORY OF HPV VACCINE

12. Epidemiological studies, made in 1990, showed that a consistent association between Human Papilloma Virus and Cervical Cancer existed.
Nearly 16 years later, in 2006, the first vaccine to prevent infection for four types of HP Virus was licensed.

13. A Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) recombinant vaccine (HPV4) was licensed for use in females by the Food and Drug Administration in 2006 and a bivalent vaccine (Types 16 & 18) (HPV2) in 2009.

14. How does it work?
Both types of vaccine,  Cervarix (GSK) and Gardasil (Merck), are inactivated vaccines.
An inactivated vaccine (or killed vaccine) consists of virus particles which are grown in culture and then killed using a method such as heat or formaldehyde

15. Mechanism of the vaccine
The HPV vaccine is based on the hollow virus like particles (VLP) that are assembled from recombinant HPV coat proteins.
The virus has a double stranded DNA and a viral shell having 72 capsomeres.
Every subunit of the virus has two protein molecules, L1and L2.

16. The proteins ensure that numerous copies are made within the host cell.
Affinity of the virus is dependant on its structure, thus such knowledge of structural components is vital for effective vaccine production.

17. Cervarix Mechanism
Cervarix is created using the L1 protein of the viral capsid 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.

18. Gardasil Mechanism
Gardasil contains recombinant VLPs assembled from the L1 proteins 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

19. Gardasil and Cervarix are designed to elicit virus-neutralizing antibody 
responses that prevent initial infection with the HPV types represented in the vaccine.
The protective effects of the vaccine are expected to last a minimum of 4.5 years after the initial vaccination

20. Therapeutic Vaccine for HPV
 In general these vaccines focus on the main HPV oncogenes, E6 and E7. Since expression of E6 and E7 is required for promoting the growth of cervical cancer cells (and cells within warts), it is hoped that immune responses against the two oncogenes might eradicate established tumors.

21. MEL-1 (or MVA-E2 Vaccine)
This working therapeutic HPV vaccine has been clinically tried in Mexico.
It is a MVA based vaccine with an e2 bovine protein added in. It has been shown to completely eliminate HPV to the point that patients test negative for the presence of HPV in blood tests.
The vaccine is officially called the MEL-1 Vaccine but also known as the MVA-E2 vaccine
Clinical trials are still underway, in mexico.

22. Clinical Trials
Efficacy
Limitations
Side effects
Future prospects and improvements
Current Research

23. Clinical Trials of Gardasil
Merck & Co. conducted a Phase III study named as (FUTURE II).
This clinical trial was a randomized double-blind study with one controlled placebo group and one vaccination group.
Over 12,000 women aged 16–26 from thirteen countries participated in the study. Each woman was injected with either Gardasil or a placebo on day 1, month 2, and month 6. In total, 6,082 women were given Gardasil and 6,075 received the placebo.

25. Subjects in the vaccine group had lower occurrence of high-grade cervical intraepithelial neoplasia (CIN) related to HPV-16 or HPV-18 than did those in the placebo group.
On February 27, 2007, clinical trials were terminated on ethical grounds, so that young women on placebo could receive Gardasil.
It is the potentially premalignant transformation and abnormal growth (dysplasia) of squamous cells on the surface of the cervix.[1] CIN is not cancer, and is usually curable.[2] Most cases of CIN remain stable, or are eliminated by the host's immune system without intervention. However a small percentage of cases progress to become cervical cancer, usually cervical squamous cell carcinoma (SCC), if left untreated.[3] The major cause of CIN is chronic infection of the cervix with the sexually transmitted human papillomavirus (HPV), especially the high-risk HPV types 16 or 18. Over 100 types of HPV have been identified. About a dozen of these types appear to cause cervical dysplasia and may lead to the development of cervical cancer. Other types cause warts.

27. Clinical Trials of Cervarix
Phase III trials have been conducted by GlaxoSmithKline, including over 18,000 women from 14 countries in Pacific Asia, Europe, Latin America and North America
In 2009 the manufacturer conducted a trial to compare the immunogenicity and safety of Cervarix with Gardasil.

28. The studies showed Cervarix generated higher levels of antibodies than Gardasil, upon testing seven months later, with twice the level for HPV type 16 and six times for HPV type 18.
Cervarix also induced twice as many memory B cells as Gardasil for both these HPV strains.

29. Efficacy
Both Gardasil and Cervarix have been shown to prevent cervical dysplasia from the high-risk HPV types 16 and 18 and some protection against a few closely related high-risk HPV types.
Other high-risk HPV types are not affected by the vaccines.

30. The protection against HPV 16 and 18 strains has lasted 5 years after vaccination for Gardasil and more than 6 years for Cervarix (7.3 years).
Gardasil also protects against low-risk HPV types 6 and 11, which do not cause cancer, but do cause genital warts.

31. Limitation
Cervarix does not provide protection against disease caused by all HPV types, nor against disease if a woman has previously been exposed to the virus through sexual activity. It is therefore recommended that women continue to adhere to cervical cancer screening procedures.
30% of cervical cancers will not be prevented by these vaccines. Gardasil also fails to treat 10% genital warts.

32. Side Effects
pain, swelling, redness, bruising, or itching where the shot was given;
mild fever, headache, dizziness, tired feeling;
nausea, vomiting, diarrhea;
sleep problems (insomnia);
runny or stuffy nose, sore throat, cough;
tooth pain, joint or muscle pain.

33. Improvement for future
The vaccines should become effective against strains other then strain 16 and 18.
The vaccines effect should last longer than 5 years. Preferably for a lifetime.
The required dosage should be reduced, from 3 dosages to only 1 dosage that protects a person for a lifetime.
The vaccine should work against curing existing HPV infections and cancer.
They should become a cancer vaccine from STD vaccines.

34. Current Research
An investigational nonavalent (types 6, 11, 16, 18, 31, 33, 45, 52, and 58) vaccine produced by Merck & Co. called V503 is awaiting approval from the FDA.
In a phase 3 clinical trial, V503 provided comparable protection to the four types that Gardasil protects against as well as a 97% reduction in cases of high-grade cervical, vulvar and vaginal diseases of five additional HPV types that are considered high-risk for developing cancer.