Sarah received the HPV vaccine Gardasil at age 15 through her school's immunization program to reduce her risk of cervical cancer later in life. The HPV vaccine works by using virus-like particles (VLPs) that are similar in structure to actual HPV viruses but are non-infectious and non-cancer causing. When exposed to these VLPs, the immune system mounts a strong antibody response against the types of HPV targeted by the vaccine. If Sarah were exposed to one of these HPV types later, her immune system would launch a rapid response from memory cells, preventing infection and damage to her cervical tissue.

1. 1. Case Study on Human PapillomaVirus vaccine
Sarah, aged15 years,has receivedafull course (three vaccinations) of Gardasil,the humanpapilloma
virus(HPV) vaccine,inthe school-basedimmunisationprogramme toreduce herlifetimeriskof cervical
cancer.1 (Reading'Defence 2'will helpyouanswerthe followingquestions).
1. Describe the primary immune response following vaccination.
The most effective HPV vaccine after the discovery of virus-like particles (VLPs). The
recombinant DNA technology was used to generate VLPs capable of performing the role of
natural virus and producing high-titers of virus neutralizing antibodies. The subcloning L1 gene
from the viral genome is done microorganisms, such as yeast. VLPs obtained are similar to the
conformation of authentic virions, are not infectious, nononcogenic and induce high levels of
type specific neutralizing antibodies.
The main characteristics of the immune response following VLPs are:
1. VLPs are highly immunogenic due to their ability to activate both innate and adaptive immune
responses and inducing high concentrations of neutralizing Ab to L1. VLPS are also remain high
over time.
2. VLPs generate a heterogeneous or polyclonal immune response: neutralizing and non-
neutralizing; immunodominant and non-immunodominat; partially cross-reactive and type-
specific type responses.
3. The antigen dose in VLPs is higher as compared to natural infection and the capsids are
straightforward visible to systemic immune responses.
4. Vaccine also triggers the immune-memory system
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988719/
2. Sarah may be exposed to one of the HPV viruses (targeted in the vaccine) when she is
older. If this was to occur:

2. a. Describe the expectedimmune response.
 The host's immune response to HPV infection (humoral immunity, mainly IgG) is generally
slow, weak and varied significantly among women. HPV antigens [E1, E2, E6, and L2] do
not induce any antibody responses in patients having acute or persistent HPV infection.
 Innate immunity perform as the first line of nonspecific defense against any pathogen
(dendritic cells, interferon-α, cytokines, neutrophils, and macrophages) and attacks by HPV
is detected by the intraepithelial dendritic cell (DC). DCs are not activated by the uptake of
HPV capsids proposing a limited role in the host's response to HPV infection .
 Most antigens are structurally complex, comprising many different epitopes or antigenic
determinants. The L1 capsid protein comprises multiple overlapping epitopes, some of which
may be immunodominant. The immune system reacts to the antigen by producing a higher
rate of neutralizing antibodies to the most reachable epitopes or to the immunodominant
types. However, in natural HPV infection the immune response is weak and type-specific.
 Natural infection triggered antibodies may not provide complete defense to HPV over period.
However, they could not differentiate the new infection from the reactivated latent ones. Host
antibodies, mostly engaged against the viral L1 protein, do not essentially protect against
subsequent infection by the identical HPV genotype.
Comparisonof humanpapillomavirustypes16,18, and 6 capsidantibodyresponsesfollowingincident
infection.CarterJJ,KoutskyLA,HughesJP,Lee SK,KuypersJ,KiviatN,GallowayDA JInfectDis.2000 Jun;
181(6):1911-9.
Human papillomavirusvirus-like particlesdonotactivate Langerhanscells:apossibleimmune escape
mechanismusedbyhumanpapillomaviruses.FauschSC,DaSilvaDM, Rudolf MP, Kast WMJ Immunol.
2002 Sep15; 169(6):3242-9.
Determinantsof humanpapillomavirus16serological conversionandpersistence inapopulation-based
cohort of 10 000 womeninCostaRica. Wang SS,SchiffmanM, HerreroR, CarreonJ, HildesheimA,
RodriguezAC,Bratti MC, ShermanME, MoralesJ,GuillenD,AlfaroM, ClaymanB,Burk RD, Viscidi RP
Br J Cancer. 2004 Oct 4; 91(7):1269-74.

3. a. Explain the effects on her cervical tissue/s.
Human papillomavirus (HPV) contaminate the genital tract. The association between some
definite oncogenic (high-risk) strains of HPV and cervical cancer is well well-known. Although
HPV is essential to the alteration of cervical epithelial cells, it is not necessary, and a diversity of
cofactors and molecular events influence to develop a cervical cancer. Precancerous lesions are
first step towards a progression of cervical cancer. Cytological and biopsy analysis is done to
confirm the disease. Early detection of high-risk HPV types may increase treatment in infected
patients.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC145302/