From Pig Viruses to Insect Vectors and New Adjuvants Meg Fisher, MD and Paul Offit, MD Disclosures

Meg Fisher has no disclosures and will be mentioning off label uses of vaccines.

Paul Offit has played a major role in the development of rotavirus vaccine Objectives Counsel parents regarding the risks and benefits of rotavirus vaccines Discuss the newest techniques and adjuvants used in producing vaccines Advise families regarding the newest ACIP recommendations The Rotavirus Vaccine Saga

Rotashield and intussusception RotaTeq, Rotarix and porcine circoviruses Post-licensure studies Human Papillomaviruses

Over 100 types Specialized for epithelia Not cytotoxic, viral genes promote replication and delay differentiation, leads to proliferative lesions (warts) Genital warts

Genital epithelium and mucosa Warts HPV 6 and 11 No cancers recognized High-risk genital

Genital epithelium and mucosa Flat warts or subclinical HPV 16, 18, 31, 45 Cervical dysplasia and cancer Epidemiology Spread person to person by close contact Asymptomatic people can transmit Anogenital – over 40 types, sexual spread Over 40% of adolescents infected Regular condom use does decrease risk Incubation unknown, probably months to yrs HPV Vaccines Virus-like particles genetically engineered Capsid proteins form empty virus shell Well tolerated and immunogenic Three dose series: 0, 1, 6 months Ongoing efficacy studies Methods Recombinant technology: genetic engineering Gardasil: Saccharomyces cerevisiae produces the capsid proteins Cervarix: Baculovirus vector in Trichoplusia ni insect cells produces the capsid proteins Capsid proteins self-assemble into virus-like particles (VLP) Adjuvants Gardasil: aluminum-containing adjuvant (Amorphous Aluminum Hydroxyphosphate Sulfate) Cervarix: AS04: 3-O-desacyl-4’- monophosphoryl lipid A (MPL) adsorbed on to aluminum (as hydroxide salt) Preservatives, Additives and Residuals Thimerosal, phenol, 2-phenoxyethanol Sugars, amino acids, proteins (gelatin, albumen, cow derived stuff) Antibiotics, formaldehyde, cellular products (egg, yeast) Gardasil (Merck)

Quadrivalent types 6, 11, 16, 18 Immunogenic in girls and boys 100% effective against persisting infection Effective in preventing genital warts Licensed 2006 for girls, 2009 for boys Cervarix (GSK) Types 16 and 18 Well tolerated, immunogenic and effective Not studied in boys Licensed 2009 for girls age 10 through 25 Recommendation: females as for Gardasil Novel production, novel adjuvant Other Cool Methods

Hepatitis B: Saccharomyces cerevisiae produces surface antigen Conjugates: antigen is attached to a protein to cause a T-cell dependent response Influenza cold adapted virus Conjugate Vaccines

T-cell dependent immune response Immune memory, booster effect Long-term protection Reduction of carriage Herd immunity Courtesy of the Centers for Disease Control and Prevention Courtesy of the Centers for Disease Control and Prevention Courtesy of the Centers for Disease Control and Prevention Menactra, Menveo

Meningococcal serotypes A, C, Y, W-135 Menactra: conjugated to diphtheria toxoid Licensed in January 2005 Menveo: conjugated to diphtheria CRM197 Licensed in February 2010 Recommendations Adolescents age 11-12 yr (pre-teen visit) Catch up all other adolescents Incoming college freshmen in dorms High risk: microbiologists, travelers, military recruits, complement deficiency, asplenia 2010 ACIP

Highest risk patients need 2 doses, 2 months apart and boosters every 3-5 years Adolescent booster at age 16 years If immunized at age 13-15, consider another dose in 5 years (up to age 21) These are not yet official

Whooping Cough Disease most severe under 6 months Coughing illness: 100 day cough Teens and young adults Paroxysmal, post-tussive vomiting Duration of cough 6 to 10 weeks Outbreaks in CA, OH, and PA Pertussis Vaccines DTP: no longer used in US DTaP: for the primary series Tdap: for teens and adults, licensed in spring of 2005, should have altered epidemiology and protect infants Tdap: Boostrix, Adacel Tetanus, diphtheria, pertussis booster For teens and adults Licensed for ages 10 to 64 years: gaps for youngest and oldest Uptake to date in adults 5.9%; healthcare workers only 13.9% 2010 ACIP

Tdap dose for under-immunized children ages 7 to 10 years Tdap dose for those over 64 years These are off label uses Still waiting for data on giving a second Tdap National Vaccine Injury Compensation Program Established by National Childhood Vaccine Injury Act No fault compensation program http://www.hrsa.gov/vaccinecompensation/ Report suspected adverse events to VAERS

Smiling is a contagious condition!