3.2 HPV, Polio, Rotavirus, RSV Vaccines

HPV: Transmission and Symptoms

DNA virus (double stranded)

Most common sexually transmitted infection in Canada • ~75% of Canadians will acquire one or more vaccine HPV types in their lifetime (3 out of 4 sexually active adults)

Usually no symptoms; may cause warts though they may be hard to see especially dependent on location

HPV Complications and Strains

Long-term HPV infection can lead to cancer of the cervix, vagina, vulva, penis, anus, mouth, and throat

HPV is the major cause of cervical and vaginal cancer in women

average of 1,350 cases of cervical cancer diagnosed/year in Canada with 400 deaths

causes almost all head and neck cancers in males < 40 years of age in Alberta

> 100 different strains • Low-risk HPV (non-oncogenic): 6, 11 • High-risk HPV (oncogenic): 16,18

How many % of all cancers are HPV associated

5%

& of vaginal, cervix, anus and oropharynx cancers linked to HPV

C = 99%

A = 84.3%

V = 69.9%

O = 35.5%

HPV Vaccine coverage

2021 National coverage was 84% for 14-year-olds receiving at least 1 dose

AB, SK, MB, NB, NS, YT in 2023: Average was 76% receiving one dose and 66.8% receiving 2 doses

HPV Vaccine Approval, mechanims, Route

2006 to reduce risk of cervical cancer

Inactivated, genetically engineered vaccine

Route: IM

HPV Vaccine Formulations

Cervarix® (HPV2) – covers HPV types 16 and 18 (not approved for males)

Gardasil® (HPV4) (discontinued)– covers HPV types 6, 11, 16 and 18

Gardasil®9 (HPV9) – covers HPV types 6, 11, 16, 18, 31, 33, 45, 52, 58

HPV Vaccine Dosing

Manufacturer dosing Gardasil 0, 2, 6 months

Manufacturer dosing for Cervarix is 0,6-12 months (Not routinely seen)

NACI (Canadian) HPV Vaccine Recommendations for ages 9-26 years

all people (inlcude pregnancy)

HPV Vaccine Dose recommendations for ages 9 to 20, 21-26 and immunocompromised.

age 9 to 20 should receive 1 dose HPV vaccine

age 21-26 should receive 2 doses (doses at least 24 weeks apart)

A 1 dose series studied in people 9 to 20 shows effective protection out to 11 years after vaccination (Studies ongoing)

A three-dose series is still recommended for those who are immunocompromised.

What HPV Vaccine should be used as covers greatest number of strains?

9vHPV

HPV Vaccine Dosing recommendations for those 27 and older

may receive the HPV vaccine in discussion with healthcare provider.

The vaccine should be given as a 2 dose schedule administered at least 24 weeks apart

HPV Public Funding in Alberta (school Vaccine regimen)

• School-based immunization (Grade 6) – HPV9 (2 doses)

• Student eligible to receive vaccine in Grade 6 continue to be eligible to receive the vaccine up to and including 26 years of age

• Males and females up to and including 26 years of age

Polio: Transmussion, Cause, Contagiousness and Immunity

Poliovirus (member of enterovirus subgroup of Picornaviridae family)

Transmission: fecal-oral route

Most infections asymptomatic or mild (90-95%), but 1-5% cause meningitis and 1% paralytic polio

Immunity develops after natural infection

Polio Vaccine: Approval, Last case of paralytic polio

Vaccine introduced in 1955

1959: last epidemic in Canada, with 2,000 cases of paralytic polio, children ages 5 to 9 years the most affected

1989: last case of paralytic polio in Canada

Polio Vaccine Efficacy, Places with ongoing endemic, and Polio monitoring

3 doses of vaccine (primary series) is 90-100% effective at preventing paralytic polio

Polio remains endemic in 2 countries (Afghanistan, Pakistan); additional countries have known or suspected transmission

can be spread by traveler's

Monitoring of wastewater is the gold standard for indicating polio in the community

Polio Outbreak (New York)

Polio outbreak in New York 2022: 1 case of paralytic Polio in an unvaccinated individual. Samples discovered in wastewater testing: New York City, Orange County, Rockland County, Sullivan County, and Nassau County

Vaccination rates as low as 60% for Polio in 2022:

• Indicates community transmission

• As of 2023 no new cases though water samples showed genetically related strains indicating likely other non-reported cases

Viral sequences indicate that it was genetic changes from a vaccine-derived live poliovirus:

• Likely from overseas where live vaccine is still used (Not used in North America for >20years)

• This meets the criteria of circulating vaccine-derived poliovirus adding the US to a list of about 30 other countries

Polio Vaccine: What does it contain, efficacy, expiry

oliomyelitis vaccine contains 3 types of wild poliovirus

Available as trivalent inactivated polio vaccine (IPV) or in a combination vaccine

Live attenuated oral polio vaccine (OPV) no longer recommended or available in Canada:

• cases of paralytic polio associated with vaccine between 1980-1995

Primary series: IPV produces immunity to all 3 types of poliovirus in > 95% following 3 doses, and close to 100% following booster

Vaccine usually has very short expiry date

Polio Vaccine Preparations include

IPV (IMOVAX® Polio)

Tdap-IPV (BOOSTRIX®-POLIO, ADACEL®-POLIO)

Polio Vaccine Recommendations in infants and children (2 months to 17 years of age)

routine infant immunization beginning at 2 months of age

Polio Vaccine Recommendations in adults

previously unimmunized: complete series of IPV

singlelifetime booster recommended for persons at increased risk of exposure (e.g., travelers to endemic areas, family of internationally adopted infants who may have been vaccinated with OPV, etc)

See Canadian Immunization Guide for additional details

Polio Vaccine for Travellers

Recommended only for travelers who are staying for >4 weeks in a current polio endemic area (updated regularly on the WHO and CDC websites)

Travelers to these countries may require a booster dose (if a record of polio vaccination in past) or an initial polio vaccine series

Patients may require an International Certificate of Vaccination

Rotavirus Cause, Transmission, Infectiousness

Non-enveloped virus (Reoviridae family)

Transmission: fecal-oral route (including fomites)

Highly infectious: small amount of virus needed and prolonged viral shedding in stool

Rotavirus Presentation, Contractility, Deaths

fever and severe vomiting and diarrhea in infants and young children

disease most severe in infants and children 3 months to 24 months (majority of hospitalizations in this group)

by 3-5 years, 95% of children have been sick with Rotavirus

worldwide, more than 500,000 deaths/year in young children are caused by Rotavirus.

Rotavirus Vaccine Approval, Efficacy and Route

Vaccine introduced in 2006

Efficacy: 85% to 98% effective against severe diarrhea

Route: oral

Rotavirus Vaccine Preparationa available

RotaTeq®: live, oral, pentavalent rotavirus vaccine (3 doses 2, 4, 6 months)

ROTARIX®: live, oral, monovalent attenuated rotavirus vaccine (2 doses at 2, 4 months) •

Rotavirus Vaccine Recommendations in healthy infants

starting immunization at 6 weeks up to and before 15 weeks of age

vaccine series must be completed before 8 months of age

Healthy, non-hospitalized preterm infants may receive based on chronological age

Safety/AEs of Rotavirus Vaccine

Common: large clinical trials did not show many differences in adverse events compared to placebo

small increased rate of diarrhea and vomiting

Rare:

Intussusception. background rate of about 34 per 100,000 per year (varies with age in first year of life); estimated risk of 1-7 excess cases per 100,000 doses in 7 days following vaccine dose

Intussusception Definition

serious condition where one part of the intestine folds into another, like a telescope, causing blockage, swelling, and cutting off blood supply, leading to potential tissue death or perforation, requiring emergency care.

Rotasheild (Discontinued) information

• Released in 1998

• Withdrawn from the market due to post-market surveillance showed increased cases of intussusception

  • These cases were associated (>80%) with a first dose starting after 90 days (catchup schedule)

  • Modeling of the recommended 3-dose series at 2, 4, and 6 months resulted in 1 case of intussusception per 11-16 thousand patients

  • A series of 2 doses in the neonatal age range projected 1 case per 38-59 thousand patients • This is only a 7% increase above the background cases of intussusception

• Therefore, we ensure that parents and doctors know to ensure that they start the rotavirus vaccines as early as possible to reduce the risk

Respiratory Syncytial Virus (RSV) Cause

• Single stranded RNA virus from the Paramyxoviridae family with humans as the only reservoir

• Infection occurs throughout life, most serious infections in the very young and elderly

RSV Transmission and Incubation

Transmission:

• Direct and indirect (contaminated hands and surfaces) contact with infectious respiratory droplets.

• Exhibits a seasonal cycle that can vary by region

Incubation: 2-8 days from exposure to symptoms

RSV Symptoms

• infections present minor symptoms in healthy adults like common cold

• Nasal congestion, cough, low grade fever and loss of appetite for 1-2 weeks

• Most common cause (20-30% of cases) of bronchiolitis and pneumonia in Infants/young children as well as severe clinical outcomes in the elderly particularly with comorbidities

• In Canada ~2% of infants are hospitalized with RSV in first year of life, in remote communities the rates can be as high as 17%

• Subsequent infections are less severe

• Infant mortality in high-income countries is low .069% with supportive care

  • Higher in older adults 5-10% increasing with age and comorbidities

RSV Risk ois increased in which populations

Almost all infants by 2 years have been exposed

• In Canada we use a combination of vaccines and monoclonal antibodies to reduce risk.

• Occurs worldwide

• The younger the infant the higher the risk, especially if comorbidities

• Risk increases with age especially over the age of 75 and with comorbid disease

• Serious outcomes are also seen in adults over 60 in nursing homes and chronic care facilities

• Higher burden of disease in northern and remote settings

Infants with these conditions have an increased risk of severe RSV in FIRST RSV season

Premature, Chronic Lung Disease, Cystic Fibrosis, Significant Chronic Cardiac Disease, Severe Immunodeficiency, Congenital Airway anomalies, Neuromuscular Disease, Down Syndrome

Infants with these conditions have an increased risk of severe RSV in SECOND RSV season

Chronic Lung Disease, Cystic Fibrosis, Significant Chronic Cardiac Disease, Severe Immunodeficiency, Congenital Airway anomalies, Neuromuscular Disease

Adults with these conditions have an increased risk of severe RSV in any RSV season

Cardiac and Pulmonary Disorders, Diabetes, Moderate to Severe Immunodeficiency, Chronic Renal Disease, Chronic Liver Disease, Neurologic or Neurodevelopmental conditions, and Class 3 Obesity or higher

RSV Vaccine Formulations

Arexvy (RSVPreF3)

Abrysvo (RSVpreF)

mRESVIA (RSV mRNA) Just approved Nov 6 2024

Arexvy Vaccine: Type, Dose

Type: Subunit Adjuvanted Vaccine

Dose: Single 0.5ml dose IM indicated for 60+ (or 50+ at increased risk)

Arexvy Vaccine Efficacy

• ~82% effective against RSV infection and ~94% against severe infection after 1 season and ~74% and 82% after 2 seasons

• Limited data supports a reduction in lab confirmed RSV RTI’s, hospitalizations in adults >60

• Efficacy beyond season 1 not clear though data suggests protection through at least 2 seasons as response wanes over time

• May consider giving to 50+ age in Metis and First Nations

• Requirement for booster doses is not yet clear

RSV Vaccine CIs

Hypersensitivity to a component of the vaccine or previous anaphylactic reaction

RSV Vaccine AEs

Injection site pain (Higher rate than other RSV vaccines likely due to adjuvanted nature), headache, fatigue and muscle/joint pain

Abrysvo vaccine Type and Dose

Subunit vaccine NO ADJUVENT

Dose: Single 0.5ml dose IM for pregnant individuals 32-36 weeks gestation, and >60 years of age

Abrysvo Vaccine Efficacy in Pregnancy

RSVpreF given to pregnant individuals results infants having a 57% decrease in hospital admission and 51% reduction in RSV RTI’s in their first RSV season

Optimally administered 2 weeks before birth to allow transplacental transport of Ab

Abrysvo Vaccine Efficacy (not in pregnancy)

~65% against RSV infection with 2 or more symptoms and ~89% against RSV infection with 3 symptoms after 1 season dropping to ~55% and 77% after 2 seasons

Limited data supports a reduction in lab confirmed RSV RTI’s, hospitalizations in adults >60

Efficacy beyond season 1 not clear though data suggests protection through at least 2 seasons as response wanes over time

May consider younger age in Metis and First Nations 50+ years of age

Requirement for booster doses is not yet clear

mRESVIA Vaccine Type and Dose

mRNA vaccine

single dose IM for those >60

mRESVIA Vaccine Storage and Efficacy

Must be frozen (like other mRNA vaccines) and stable for 30 days at fridge temps and 24 hours at room temps

Efficacy: ~83% against RSV infection with 2 or more symptoms and ~82% against RSV infection with 3 symptoms after 3.7 months dropping to ~63% and 63% after 8.6 months

RSV Vaccine NACI Recommendations for those 75 or older

recommend vaccine, particularly for those at higher risk of severe disease. (List 1)

RSV Vaccine NACI Recommendations for those 50-74

individual decision with their HCP

A single dose of RSVPreF3, RSVpreF or mRNA-1345 can be used in adults 60 to 74 years of age.

A single dose of RSVPreF3 can be used in adults 50 to 74 years of age.

People at risk (List 1) get more benefit

RSV Vaccine List 1

• Cardiac or pulmonary disorders (includes chronic obstructive pulmonary disease asthma, cystic fibrosis, and conditions affecting ability to clear airway secretions)

• Diabetes mellitus and other metabolic diseases

• Moderate and severe immunodeficiency (refer to the list of immunocompromising conditions developed for COVID-19)

• Chronic renal disease

• Chronic liver disease

• Neurologic or neurodevelopmental conditions (includes neuromuscular, neurovascular, neurodegenerative [e.g., dementia], neurodevelopmental conditions, and seizure disorders, but excludes migraines and psychiatric conditions without neurological conditions)

• Class 3 obesity (defined as BMI of 40 kg/m2 and over)

RSV Coverage

Abrysvo only:

>70 years of age no other conditions

>60 years of age in a continuing care facility or indigenous

RSV Vaccine for Pregnant Individuals

May be given regardless of past RSV infection

Vaccination should occur between 32 and 36 weeks and at least 2 weeks before birth for infants expected to be born during RSV season (If birth occurs before 2 weeks is complete mononclonal Ab’s should be administered)

Some studies have found increased risk of preterm births among RSVpreF recipients (not observed in high income countries)

RSVpreF may be considered for pregnant individuals in consultation with care provider in advance of or during RSV season to reduce disease risk in infant (not requireed if monocloonal Ab will be administerd at birth)