Vaccines Against Viral Vaccines Against Viral InfectionInfection

Austin FollettAustin Follett

Medicinal ChemistryMedicinal Chemistry

Anti-Viral VaccinesAnti-Viral Vaccines

1.1. HistoryHistory2.2. Vaccine typesVaccine types3.3. How they workHow they work4.4. Recommended ScheduleRecommended Schedule5.5. Specific VaccinesSpecific Vaccines

1.1. FluFlu2.2. HIV/AIDSHIV/AIDS3.3. Human Papillomavirus (HPV)Human Papillomavirus (HPV)

6.6. To stick or not to stick?To stick or not to stick?

History of VaccinesHistory of Vaccines

• Chinese inoculated themselves against smallpox before 200 Chinese inoculated themselves against smallpox before 200 B.C.B.C.

• Edward Jenner inoculated against smallpox with cowpox in Edward Jenner inoculated against smallpox with cowpox in 17961796

• Vaccination comes from Latin (vacca– cow)Vaccination comes from Latin (vacca– cow)• Louis Pasteur took the concept and applied it to prevent Louis Pasteur took the concept and applied it to prevent

against anthrax and viral rabiesagainst anthrax and viral rabies• 1988: W.H.O. targets polio for eradication1988: W.H.O. targets polio for eradication• 2000: Global Alliance for Vaccines and Immunization 2000: Global Alliance for Vaccines and Immunization

formed; strengthens routine vaccinations in countries with formed; strengthens routine vaccinations in countries with GDP below $1000GDP below $1000

• Currently, nearly two dozen vaccines are available for use Currently, nearly two dozen vaccines are available for use in the United Statesin the United States

Types of Viral VaccinesTypes of Viral Vaccines

1.1. Inactivated: Virus particles are Inactivated: Virus particles are grown then killed by either heat or grown then killed by either heat or formaldehyde formaldehyde

2.2. Attentuated: Live, weakened form of Attentuated: Live, weakened form of the virus particlesthe virus particles

3.3. Subunit: Only given antigen of virusSubunit: Only given antigen of virus1.1. Isolation of specific proteinIsolation of specific protein2.2. Recombinant administrationRecombinant administration

How vaccines workHow vaccines work

Vaccination ScheduleVaccination Schedule

• By age two, children are By age two, children are recommended to have the following recommended to have the following vaccines by the Advisory Committee vaccines by the Advisory Committee on Immunization Practices:on Immunization Practices:– Hepatitis A & B, Polio, Measles, Mumps, Hepatitis A & B, Polio, Measles, Mumps,

Rubella, Diptheria, Pertussis, Tetanus, Rubella, Diptheria, Pertussis, Tetanus, HiB, Chicken Pox, Rotavirus, Influenza, HiB, Chicken Pox, Rotavirus, Influenza, Meningococcal disease, and PneumoniaMeningococcal disease, and Pneumonia

Flu VaccineFlu Vaccine• Virus has 8 piece Virus has 8 piece

genome undergoes genome undergoes antigenic driftantigenic drift

• The flu kills 36,000 in The flu kills 36,000 in the US annuallythe US annually

• Flu vaccine is an Flu vaccine is an educated guess of the educated guess of the most probable form of most probable form of virusvirus

• Two main types:Two main types:– Flu shot: inactivated Flu shot: inactivated

vaccinevaccine– Nasal-spray: attentuated Nasal-spray: attentuated

vaccinevaccine

Should you get vaccinated?Should you get vaccinated?

• Yes, if you are at high risk or care for Yes, if you are at high risk or care for someone who issomeone who is

• No, if you are allergic to chicken eggs or No, if you are allergic to chicken eggs or are otherwise immunocompromisedare otherwise immunocompromised

• Side effects:Side effects:– Possible virulence from nasal-sprayPossible virulence from nasal-spray– Soreness, rednessSoreness, redness– Low-grade feverLow-grade fever– AchesAches

HIV VaccineHIV Vaccine

• An effective HIV Vaccine would allow the An effective HIV Vaccine would allow the body to completely rid itself of the virus body to completely rid itself of the virus and/or control it to prevent infection and and/or control it to prevent infection and transmissiontransmission

• Three types being used: subunit, Three types being used: subunit, recombinant, and DNA vaccinesrecombinant, and DNA vaccines

• http://www.hopkins-aids.edu/hiv_lifecycle/http://www.hopkins-aids.edu/hiv_lifecycle/hivcycle_txt.htmlhivcycle_txt.html

HIV Methods of PreventionHIV Methods of Prevention

• Prevent fusion to host cellPrevent fusion to host cell

• Inhibit reverse transcriptaseInhibit reverse transcriptase

• Inhibit integrase: no viral integration Inhibit integrase: no viral integration into host genomeinto host genome

• Target protease: prevent polypeptide Target protease: prevent polypeptide cleavage, functional HIV proteinscleavage, functional HIV proteins

• Prevent release from host cellPrevent release from host cell

Where’s the vaccine?Where’s the vaccine?

• Several challenges arise with Several challenges arise with development:development:– HIV continually mutates and recombinesHIV continually mutates and recombines– HIV infects Helper T cellsHIV infects Helper T cells– Can be transmitted as both free virus and in Can be transmitted as both free virus and in

infected cellsinfected cells– Researchers are unsure what constitutes an Researchers are unsure what constitutes an

effective immune response to HIVeffective immune response to HIV– No ideal animal model for testing existsNo ideal animal model for testing exists– Possibility that HIV is not the true cause for Possibility that HIV is not the true cause for

AIDSAIDS

Human Papillomavirus Human Papillomavirus VaccineVaccine• HPV is required in the HPV is required in the

development of nearly all development of nearly all types of cervical cancertypes of cervical cancer

• Vaccination prevents initial Vaccination prevents initial infection by several of the infection by several of the most commonly sexually most commonly sexually transmitted HPV typestransmitted HPV types

• Estimated that 50% of men Estimated that 50% of men and women will become and women will become infected with one of the infected with one of the sexually transmitted HPV sexually transmitted HPV types during adulthood.types during adulthood.

• Along with cervical cancer, Along with cervical cancer, HPV can cause skin and HPV can cause skin and genital warts as well as anal genital warts as well as anal cancer and penile cancercancer and penile cancer

The VaccineThe Vaccine

• All types of HPV do not All types of HPV do not cause cancer, but a cause cancer, but a vaccine has been vaccine has been developed that protects developed that protects against types 6, 11, 16 against types 6, 11, 16 and 18, which cause 70% and 18, which cause 70% of cervical cancers and of cervical cancers and 90% of genital warts 90% of genital warts combinedcombined

• However, other types However, other types can cause the cancer, so can cause the cancer, so Pap smears are Pap smears are recommended to prevent recommended to prevent cancer developmentcancer development

GardasilGardasil

• On February 2, 2007 Texas Governor Rick Perry mandated On February 2, 2007 Texas Governor Rick Perry mandated that all school girls going into sixth grade be vaccinatedthat all school girls going into sixth grade be vaccinated

• Studies have only been done in short duration, long-term Studies have only been done in short duration, long-term impact unknownimpact unknown

• In 2006, estimated that 9,700 women developed cervical In 2006, estimated that 9,700 women developed cervical cancer, 38% diedcancer, 38% died

• Although all cervical cancer types are not covered by this Although all cervical cancer types are not covered by this vaccine, this prevalence would be greatly reduced by vaccine, this prevalence would be greatly reduced by widespread vaccinationwidespread vaccination

• Currently, multiple groups nationwide question the value of Currently, multiple groups nationwide question the value of the vaccine as a whole; safety issues seem to have fallen the vaccine as a whole; safety issues seem to have fallen under the importance of speed.under the importance of speed.

• In addition, other high-risk HPV types can circumvent the In addition, other high-risk HPV types can circumvent the vaccine completely, reducing its effectiveness.vaccine completely, reducing its effectiveness.

Controversy:Controversy:To Stick or Not To Stick?To Stick or Not To Stick?

To:To:• Vaccinations prevent Vaccinations prevent

viral infections, most viral infections, most effective way of effective way of

disease preventiondisease prevention• Cost-effective method Cost-effective method

to manage healthcareto manage healthcare• Herd immunity could Herd immunity could

extend to those that extend to those that don’t get the vaccinedon’t get the vaccine

Not to:Not to:• Certain vaccinations Certain vaccinations

have not been tested have not been tested completelycompletely

• Compulsory Compulsory vaccination represents vaccination represents excessive government excessive government

interactioninteraction• Childhood vaccinations Childhood vaccinations

contain mercury, which contain mercury, which has a possible has a possible

connection with autism connection with autism (MMR, DTP, HiB, Hep. (MMR, DTP, HiB, Hep.

B)B)

Thank you! Thank you!

Be smart about your Be smart about your vaccinations!vaccinations!