Larson HPV Vaccines

What does it mean that HPV is a Naked DNA Virus?

• Non-enveloped

  • Composed of the capsid protein called L1

  • L stands for “late” as in it's a late/structural gene

• L1 spontaneously self-assembles

  • Does not require any other viral proteins to assemble

How does HPV enter the cell?

• Conformational changes in capsid promote association with a secondary receptor on epithelial cells

• Virion internalized by endocytosis

Once inside the cell, viral capsid proteins _____

Hide by inserting into membrane vesicle and are transported to the nucleus

What happens when the host cell infected with HPV divides?

Promyelocytic leukemia (PML) nuclear bodies reform in association with encapsulated virus

• Important for the establishment of infection

• PMLs are usually antiviral, but in this case, they protect the viral DNA

What do E1 and E2 proteins do in the pathogenesis of HPV?

Replicate the HPV genome as extrachromosomal plasmids

What do E5, E6, E7 proteins do in the pathogenesis of HPV?

Promote viral life cycle

• Induce cell cycle re-entry and delay differentiation

• Virion production requires fully differentiated keratinocytes

How does cell-mediated immunity recognize HPV-infected cells?

1. Local activation of APCs

2. Activated APCs migrate to lymph node

3. Antigen presentation by APCs and stimulation of CD8 T cells and B cells by CD4 T cells

4. Recruitment of NK cells and activated APCs into the infected tissue

5. CD8 T cell infiltration and clearance of viral infection

6. Secretion of neutralizing antibodies (nAbs) and neutralizing of viral particles

   • New HPV infection prevented by nAb

What do E6 and E7 proteins do in the oncogenesis of HPV?

Deregulate cell cycle control

• Less well differentiated lower layers of the lesion

• Creates genomic instability (higher frequencies of mutations)

What does the Gardasil 9 vaccine for HPV contain?

• Adjuvant - Aluminum hydroxyphosphate sulfate

  • Most aluminum exposure is through diet and antacids

  • Low doses of aluminum salts can act as adjuvants

  • Stimulates a specific antibody response

• Antigen - Virus-like particles (VLPs)

  • Composed of only one viral protein

  • No genetic material (no DNA)

• Gardasil does NOT contain live virus

Are virus-like particles infectious?

• No, they do not contain any DNA or other proteins

• They are also not oncogenic

What does it mean that virus-like particles are highly immunogenic?

Produce high levels of antibodies and B cell memory

• Some antibodies are crossprotective against other HPV strains that are not seen in the vaccines

Why does the Gardasil 9 HPV vaccine produce a better antibody response than natural infection?

Intramuscular administration allows the virus-like particles to reach the lymphatics and lymph nodes

• Greater antigen presentation and cell mediated immunity in the lymph nodes

Who can’t receive the Gardasil 9 HPV vaccine?

• Someone who had a life-threatening reaction to a prior dose of the vaccine

• Someone who had a life-threatening reaction to yeast

  • Yeast is used to generate virus-like particles

What is the main limitation of the Gardasil HPV vaccine?

The vaccine is prophylactic, so it is effective at preventing HPV prior to exposure