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Human Papilloma Virus Vaccine (PATHOGENECITY (Transmission (Perinatal…
Human Papilloma Virus Vaccine
PATHOGENECITY
Signs and Symptoms
Genital warts
small stem-like protrusions
flat lesions
caulifower-like bumps
in women, usually appears on vulva but can also found at cervix and in vagina
in men, appear on penis and scrotum or around anus
Common warts
rough, raised bumps on hand
occurs on hands and fingers
Flat warts
flat-topped but slightly raised lesions
appear on face for children, legs for women and beard on men
Plantar warts
grainy, hard bumps
grow on heels or balls of feet
Diagnosis
Acetic Acid Solution Test (identify unseen lesions)
Pap Test
(reveal abnormalities that lead to cancer)
DNA Test (recognizes high-risk DNA of HPV linked to genital cancers)
Transmission
Sexually transmitted (oral, anal, vaginal sex)
Perinatal transmission; from mother to child during birth
Transmission of HPV types 6 and 11 can result in the development of of a very rare disease known as juvenile-onset recurrent respiratory papillomatosis (JORRP).
Sharing of possibly contaminated objects, for example, razors
Genital infection
Statistics
During 2011–2014, prevalence of any oral human papillomavirus (HPV) for adults aged 18–69 was 7.3%; high-risk HPV was 4.0%
Prevalence of any and high-risk oral HPV was lowest among non-Hispanic Asian adults; any oral HPV was highest among non-Hispanic black adults
Prevalence of any and high-risk oral HPV was higher in men than women except for high-risk HPV among Asian adults
During 2013–2014, prevalence of any and high-risk genital HPV for adults aged 18–59 was 45.2% and 25.1% in men and 39.9% and 20.4% in women, respectively
Prevalence of any and high-risk genital HPV was lower among non-Hispanic Asian and higher among non-Hispanic black than both non-Hispanic white and Hispanic men and women
Prevention
HPV vaccines (Gardasil 9)
If sexually active, use latex condom
Be in a mutually monogamous sexual relationship
What is HPV
2 groups of HPV
Oncogenic
HPV-16 and HPV-18
low-grade cervical cellular changes
high risk types of infection
high-grade cervical cellular changes
causes cervical cancer
Non-cogenic
HPV-6 and HPV-11
causes genital warts and laryngeal papillomatosis
low risk types of infections
There are 170 types of known HPV. More than 40 types are transmitted through sexual contact and infect the anus and genitals. Risk factors include early age of first sexual intercourse, multiple partners, smoking, and poor immune function.
HPV stands for Human papillomavirus, a DNA virus from the papillomavirus family. It is the most viral infection of the reproductive tract. HPV specifically infect the cutaneous and mucosal epithelium.
History
In 2006, the first preventive vaccine known as Cervarix was first developed by researchers at the University of Queensland, Georgetown University Medical Center, University of Rochester, and the U.S. National Cancer Institute
Harald zur Hausen, a German virologist
HPV was first discovered in 1956 by a group of scientists. In 1984, Harald zur Hausen discovered, cloned, and attributed cervical cancer to HPV 16 and 18.
In 2014, a vaccine called Gardasil 9 was introduced to protect females between the ages of 9 and 26 and males between the ages of 9 and 15 against nine strains of HPV
Treatment
Warts
Salicylic acid. For use on common warts, salicylic acid work by removing layers of a wart a little at a time.
Imiquimod. This prescription cream helps enhance immune system's ability to fight HPV
Trichloroacetic acid. This chemical treatment burns off warts on the palms, soles and genitals
Podofilox. Another topical prescription, podofilox works by destroying genital wart tissue.
Cervical cancer
radiotherapy
surgical removal
chemotherapy
Cervical cancer can be cured if diagnosed at an early stage.
Characteristics
Papillomaviruses replicate exclusively in the basal layer of the body surface tissues. All known papillomavirus types infect a particular body surface, typically the skin or mucosal epithelium of the genitals, anus, mouth, or airways.
The genome encodes for 6 open reading frames proteins (ORF) responsible for virus replication and 2 late proteins, L1 and L2, which are the viral structural proteins.
All viral ORFs are encoded on one DNA strand
HPV is a small, non-enveloped deoxyribonucleic acid (DNA) virus that belongs to the family of Papillomaviruses
Papillomaviruses are usually considered as highly host- and tissue-tropic, and are thought to rarely be transmitted between species
After the host cell is infected, early promoter is activated and a polycistronic primary RNA containing all six early ORFs is transcribed which then undergo undergoes active RNA splicing to generate multiple isoforms of mRNAs
MICROBIAL GENETICS
Types of HPV Vaccine
Cervarix (Bivalent)
contains purified protein or antigen for two types of high risk genotypes HPV (types 16 and 18).
The vaccine antigens are HPV-16 and HPV-18 L1 virus-like particles (VLPs) made from baculovirus expression vector system (BEVS).
developed by GlaxoSmithKline
Benefits
highly immunogenic
capable of generating high titers of neutralizing antibody to the HPV types included in the vaccine.
inducing protection from persistent HPV injection and HPV-related lesions
well tolerated
Characteristics
Requires three doses at the following time points: zero, two and six months.
May offer some cross-protection against other cancer-causing HPV types, including 31 and 45.
Active against four HPV types: 6 and 11 (common cause of genital warts), 16 and 18 (common oncogenic types).
Approved for prevention of genital warts in males and females, and for prevention of vulvar and vaginal intraepithelial neoplasias.
Gardasil (Quadrivalent)
contains antigen of high risk genotypes human papillomavirus (types 16 and 18) and low risk genotypes (types 6 and 11).
A quadrivalent vaccine comprised of HPV types 6, 11, 16 and 18 expressed and purified from yeast cells containing the specific L1 expression plasmids.
developed by Merck, approved by US, FDA.
Benefit
inducing nearly complete protection from persistent HPV infection and CIN lesions associated with these four (6, 11, 16 & 18) HPV genotypes
Characteristics
Active against two HPV types: 16 and 18.
Requires three doses at the following time points: zero, two and six months.
May offer some cross-protection against other cancer-causing HPV types, including 31, 33, 45, and 52.
Contains a novel adjuvant that may be responsible for greater antibody response compared with the quadrivalent vaccine
Genome Characteristics of HPV
Region
Early (E) - encodes for viral regulatory proteins
E1, E2, E3, E4, E5, E6, E7, and E8
Late (L) - encodes for viral capsid proteins
L1 - major capsid protein
L2 - minor capsid protein, recruits L1
Noncoding long control (LCR) - regulates transcription and replication of viral DNA
consist of 72 capsomere on its surface
circular, nonenveloped, double stranded DNA virus
Vaccine Production
Viral L1 gene is inserted into a plasmid
The host cells produce the HPV L1 major capsid protein
The plasmid is incorporated into a yeast or insect host cell using recombinant DNA technology
These proteins will asssemble to form viral-like particle (VLP)
The VLPs are harvested and purified for use in the vaccines
HPV vaccine is a non-infectious recombinant vaccine comprised of the L1 protein assembled into VLPs
IMMUNOLOGY
Host response to infection
Humoral immune response
Weak
Begin with maturation of B cells
interection dependent with:
cytokine profile secreted by
T-helper cells
Resultant antibodies will neutralize and opsonize foreign
antigen for destruction, preventing infection of susceptible host cells
Antigen presenting cells (APCs)
Mostly resolve spontaneously
No viremic phase
Immune reponse needs to be initiated at the site of infection
Infection is not cytolytic
Low levels of viral gene expression in the lower layers of the epithelium
Lack of cell death or necrosis
Limited innate immune response
Result in a delayed adaptive immune
response to initial papillomavirus infection
By vaccine administration
L1 is taken up to regional lymph nodes
HPV immune evasion mechanisms
that naturally occur are overcome.
Acquired immune response
B and T cells generation depend upon initial presentation of antigen by dendritic cell (DC) to the naive T lymphocyte
T cells activation upon viral protein regocnition
Production of additional cytokines that induce growth and maturation of B cells
Toll-like receptor (TLR) activation and signaling contribute to the activation of dendritic cells for antigen presentation and the primary activation of B cells
Mediated by B and T cells activity.
Innate immune response
Immediate and non-specific
Lysed virus-infected cell
Cytokines produced promote further innate and adaptive response
HPV L1 Vaccines
Unknown mechanisms of action
Current hypotheses based in rabbits and dogs
VLPs are rapidly bound by myeloid DCs and B lymphocytes
Signal via TLR dependant pathways essential for B cell activation and antibody generation
Direct action protection of serum antibodies transudating and exudating to the site of infection at the cervix
Passively immunized animals with purified serum IgG were completely protected against viral high dose
Adjuvants
Function:
Increase VLP immunogenicity by inducing cytokines or chemokines
Act directly or indirectly on helper lymphocytes to modulate immune response
Increase antigen uptake and maturation of APC
Accelerate the generation of robust immune responses
Induce local mucosal immune responses
Generate antibodies with enhanced avidity
and neutralizing capacity
Elicit the response of cytotoxic T cells
Increase the response rate in
low-responder individuals
Reduce the required amount of antigen necessary to generate the desired immune response
Quadrivalent
AAHS
Licensed with the approval of PedvaxHIB®
Has extensive, proven and predictable safety profile
Improves neutralizing antibody titres in a monkey model
Lowest dose formulation which elicited similar immune responses to the higher dose formulations
Bivalent
AS04
Purified lipopolysaccharide modified endotoxin from the wall of bacteria(Salmonella minnesota)
Monophosphoryl lipid A
Used in other vaccines manufactured such as HBV and a herpes simplex virus
Clinical trial proven excellent safety profile in administered doses
Induces higher antibody response at multiple dose timepoints
Also induces a higher frequency of memory B cells
Types
Recombinant vaccine
Cervarix (Bivalent)
For use in girls as young as age 9 to 26 years old
Prevent cervical precancers and cervical cancers
Side effects:redness, swelling and pain at the injection site, headache, gastrointestinal symptoms and fatigue
Recommended routine vaccination of 3 doses on a schedule of 0, 1 and 6 months
Administration:0.5 mL as Intramuscular injection (IM) only at the deltoid region of the upper arm or in the higher anterolateral area of the thigh
Gardasil (Quadrivalent)
For use in girls as young as age 9 to 26 years old
To prevent cervical precancers, cervical cancers, vulvar precancers and vaginal precancers, as well as anogenital warts
Also prevention of anogenital warts in males
Recommended routine vaccination of females aged 11 to 26 years with 3 doses on a schedule of 0, 2 and 6 months
Side effects:chronic fatigue and headache or dizziness, numbness, muscle pain, nausea and muscle weakness
Administration:0.5 mL as Intramuscular injection (IM) only at the deltoid region of the upper arm or in the higher anterolateral area of the thigh
Effectiveness
Have not been found to effectively clear existing HPV infections
Or treat HPV-related diseases
Designed for prophylactic (preventative) use
