Vaccinology Circa 1796I. Smallpox

II. Edward Jenner- Observation

III. A natural “vaccine” – Vaccinia

A. Milk maids did not catch smallpox- observation

B. Inculated Thomas Phipps – 8 year old boy

• Inoculated with cowpox on 5/14/1796 causing a single blister

• Inoculated Thomas Phipps on 7/1/1796 with smallpox matter No disease!

Louis Pasteur(b) 12/27/1822- (d) 9/28/18951) Rabies Vaccine

1882-18852) Principles of Vaccination 3) Microbial fermentation4) Pasteurization – milk and wine Industry 5) Alhumbert Prize 1862

– Disproving spontaneous generation 6) Anthrax Vaccine

– Exposed bacillus anthracis to potassium dichromeate

Louis Pasteur

• “Vaccines”- A weakened form of the disease causing immunity to their virulent version”.

• The artificially weakened diseases, were termed “vaccines” by Pasteur in honor of Edward Jenner

Rabies Vaccine • Emile Roux- French Doctor working with

Pasteur used a killed vaccine obtained by desiccating the spinal cord of infected rabbits.

• Vaccine tested in 50 dogs before its first human trial

• L. Pasteur used this on Joseph Meister- 9 years old on 7/6/1895 after he was mauled by a rabid dog

• Joseph Meister was in good health 3 months later

• Louis Pasteur was criticized as he was not a physician

• The successful vaccination resolved the legal disputes and was an important advance in immunology / vaccinology, establishing the significant of vaccines

• Pasteur Institute

Immune Response • Intelligence gathering Dendritic cells

• Command/ control -> CD4 T-cell

• Effector Cells CD8 ->Cellular cytotoxicity NK -> Cellular Cytotoxicity B cells -> Antibodies

• Non specific -Complement- Signals effector cells; Causes osmotic lysis

Live Viral Vaccines • Vaccinia (smallpox)• Measles / mumps/ Rubella• Varicella• Rotavirus • Sabin Polio Virus• Live attenuated Influenza Virus • Yellow fever vaccine• Japanese B encephalitis

Inactivated Subunit – viral vaccine

• Hepatitis B• Influenza • Salk Polio virus• Human Papilloma virus

Bacterial Vaccines against toxins

• Tetanus toxoid • Diphtheria vaccine

Polysaccharide Conjugate

• Pneumococcal

• Meningococcal

Whole Killed /fractionated

• Pertussis

• Anthrax

Polio• Inactivated (Salk)

3 vaccines doses given by injection -> IgG

• Live (Sabin)One dose orallyIgG and IgARisk of vaccine associated polio

Varicella Vaccine

Varicella Vaccine (V. Zoster)

Live attenuated vaccine

1) Herpes virus integrates for life

2) Cytotoxic T-cells control reactivation,

3) Antibody also conveys protection

Human PapillomavirusCauses cervical cancer and warts

•100 strains, no cross protection

•DNA Virus that integrates virus like particles revolutionized the field. (2 Licensed vaccines)

Used in Men and Women – Boys and Girls age 11-12

Pertussis Vaccine• Whole killed • Reactogenic • 5 doses for protection • Acellular 3 to 5 purified bacterial antigens• Better safety profile • 5 doses for protection

Adjuvant 1. Non-Specific enhancer of immune response

2. Stimulates antigen uptake by Dendritic cells

3. Reduces amount of Antigen needed

4. Promotes cross protective responses

Vaccinology to Immunology• Current successful vaccines are empirically derived –e.g., Jenner and

Pasteur

• Advances in immunology demonstrate a path from innate immunity to adaptive immunity

• PRR (pattern recognition receptors)

• Recognize PAMP (pathogen associated molecular pattern) causing cytokine release leading to adaptive immune responses.

Age Related Immune Deficiency Age related defects in Cellular Immunity

1) Thymic Involution and decreased immune response to new antigens 2) Accumulation of highly differentiated effector T-cells restricts the diversity of the T-cell immune repertoire and the ability to respond to new threats.

Age Related Immune Deficiency Age Related Defect in B-cell immunity 1) Reduced B-cell Precursor production with loss of naïve B-cells and reduced diversity of the B-cell immune repertoire.

2) Defects in isotype switching and somatic hypermutation decreases antibody affinity

New Approaches to protection ofOlder Adults against Vaccine preventable diseases 1) AdjuvantsConjugated pneumococcal vaccine

2) Higher Antigen Content Single dose versus high dose (4x hemagglutinin titer) influenza vaccine

3) Immunize persons who are potential sources of infection/ healthcare providers and personal contacts.

Travel - Risk Groups

1) Diseases transmitted by insect vectors

2) Diseases transmitted by contaminated food and water

3) Diseases transmitted by contaminated soil, water, and air

4) Diseases associated with behaviors of individuals or groups

Diseases associated with behaviors 1) Violation of political, cultural, religious or customary practice- repercussions vary2) Inadequate knowledge of safe and unsafe locations 3) Exposures to blood /body fluid

– Missionary work –HIV, Hep B, Hep C, Ebola– Bitten by carnivorous animal

• Rabies – Sexual tourism

4) Need for health insurance rider5) Personal trauma (adventure travel) risks unique to the activity

Adventure Travel Risk Varies with activity

1) Diving: the bends, air emboli; CNS toxicity, bone infarction

2) Climbing more than 9000 feet- High Altitude pulmonary Edema, high altitude cerebral edema, falls, frostbite, etc.

3) Rafting, parasailing, personal watercraft, snorkeling- risks are unique to the activity

4) Venomous reptile and insect bites related to trekking, tick born illnesses, etc.

Contaminated Soil/ Water and Air1) Tuberculosis in areas with crowding and low socio-economic status 2) Geohelminths – worm infections related to larvae in soil that can penetrate

human skin including round worms, whipworms, hook worms, thread worms ( stronglyloides)

3) Water exposure Schistosomaiasis

4) Wear shoes, protective clothing in fresh water

Diseases related to ingestion of contaminated food and water: Hepatitis A, flukes, cestodes roundworms, etc.

1) Water preparation Boiling –heat source, time

2) Bottled –reliable, supplier, weight if trekking

3) Filtration- expensive, learn to use

4) Iodine or Chlorine

Water may seem unpalatable, taste like iodine or chlorine and contain sediments

Food preparation • Vegetables

– cook before serving • Meats

– cook through to kill encysted parasites • Peelable fruit

– ok to eat, take care in peeling so as not to contaminate

Diseases associated with insect vectors 1) Malaria

2) Flaviviruses – Yellow fever – fever, jaundice – Dengue fever myalgias / arthralgias for 10-12 days- “bone-break” fever– Chikungunya Virus- myalgias / arthralgias for > 6 months – West Nile Virus – aseptic meningitis, Guillain-Barre syndrome – Zika Virus- Microcephaly ADEM; pregnancy and conception precautions – Tick borne encephalitis

Diseases associated with insect vectors 3) Leishmaniasis- Sand flies

– Middle East and Mediterranean4) Bartonellosis – Sand flies

– Peru5) Chagas disease

– Reduviid bug– Trypanosomes- South Central America to Argentina bugs live in mud in walls of huts.

6) African trypanosomiasis – TseTse flu, sleeping sickness– No man's land

7) River Blindness – Onchocerciasis– Africa

8.) Elephantiasis- wuchereria bancrofti– South Pacific Islands

Infection Risks USA and Travel 1) Hantavirus- Urine of infected mice

– cabins in 4 corners area• N.M, Arizona, Nevada and Colorado

2) Q-fever, aerosolized placental – Material – Cattle, sheep and goats

3) Tularemia francisella tularensis1) Deer flies, ticks, direct exposure-to rabbits

4) Plague- Yersinia pestis– Western US – Exposure to fleas while trekking

5) Lyme Disease – Borrelia species• Tick born; data shown no benefit to prolonged courses of antibiotic

therapy

6) Babesiosis- immunocompromised

7) Relapsing fever- Borrelia recurrentis• Flying squirrel

8) Angylostrongyloides cantonensis• slugs in Hawaii, Pacific Islands , avoid snails• causes eosinophilic meningitis

Special considerations • Acclimatization for climbing more than 9,000 feet, use diamox

• Rifaximin or levofloxacin self -treatment for traveler’s diarrhea

• Mobilization and a baby aspirin for a long plane flight

• Pay attention to US State Department warnings for US travel

Questions?

• myHealth@SC (Patient Health Portal) is a secure, convenient way to manage your personal health care and communicate directly with your doctor’s office online

• This free self-service allows you to update your health history and check your personal health records online anywhere, anytime using a computer, smartphone or tablet

What is the Portal?

How can the Portal Benefit Me?• Review electronic portions of your personal health record, including office visits, physician

notes, conditions, and medications• View test and lab results• Send and receive messages from your doctor’s office• Request appointments & prescription refills when it’s convenient for you• Receive reminders for preventive and follow-up care• Download, fax and e-mail select health information such as immunization history, school exam

forms and more• Share your physicians’ profiles with your friends, family and contacts directly from your account• Proxy access allows access to the health information of another person (i.e., minor child,

dependent adult, spouse, legal guardian).• View records from other participating organizations• Pay your bill online

Patient Portal Benefits When Traveling

Access to Medical Records• Access through your patient

portal will provide non-Clinic Providers with your health conditions, current medications, immunizations, and any allergies while traveling.

Requesting Medication Refills• Requesting a prescription

refill from your Clinic Provider and selecting an out-of-town pharmacy directly from your patient portal.

How Do I Sign Up For myHealth@SC?1. Visit any Springfield Clinic office and present your photo ID during

your office visit and reception staff will verify your identity, OR

2. Register online at www.springfieldclinic.com. Click on MYHEALTH@SC tab and select Online Registration. (Note – requests for proxy access must be handled in person, not online)

3. Within 5-7 business days, you will receive an email invitation from noreply@followmyhealth.com to activate your myHealth@SC account. Follow instructions for completing the registration process.

myHealth@SC Portal Support our • To learn more visit,

www.SpringfieldClinic.com/myHealthAtSC

• Portal Support: SpringfieldClinic.com/myHealthSupport

• Call our help desk staff: 1.855.264.2872 (toll free)