Vaccines P1 (Fouty)

Additional Material (Lecture)

Variola major

Smallpox

scraped lesions from infect and put in nose or skin of uninfected

Variolation

People inoculated through variolation could still spread

smallpox

but individual mortality was reduced to 1-2%

1774 use of cowpox to protect against small pox by _______ but in 1796 more formally done by inoculation by ________

Benjamin Jesty; Edward Jenner 

Jenner’s experiment

Inoculated gardener’s son with cowpox

6 weeks later inoculated him with smallpox via variolation

Smallpox vaccine changed from cowpox to _____ virus

Vaccinia

both live viruses of same genus orthopoxvirus

1950 ____ begins intensive international effort to eradicate smallpox

WHO

______ smallpox was eradicated from the world 

1978 only stock solutions still exist 

Pasteur’s model of rabies vaccine

desiccated spinal cords from rabies infected rabbits

Pasteur gave a series of SQ injections containing minced desiccated rabies-infected rabbit spinal cords to Joseph Meister

Injected progressively less-desiccated (fresher_ rabbit spinal cord over time

Boy survived rabies

Strangling angel of children

Diphtheria

Pseudomembrane occlude upper airway

Clinical diphtheria is caused by a 

toxigenic strain (phage contaminated diphtheria)

Diphtheria+ phage + low bacterial irons=________ which inhibits

diphtheria toxin

protein synthesis

Diphtheria toxin was the first described

exotoxin

______ inactivated diphtheria toxin injected into guinea pigs protected them from subsequent toxin injections

Heat

serum from an animal given heat-inactivated Diptheria toxin protected an unimmunized animal that was given virulent toxin

Anti-toxin 

In 1891 Emil von Behring used animal immune serum to treat a child with diphtheria

Child survived

variolation: live attenuated virus

Vaccination: live cowpox/vaccinia virus

Smallpox

Inactivated (dead) virus

Rabies

Passive immunity (antibody therapy)

Diphtheria 

The individual receives protective antibodies from other source

Passive immunity

Natural method of passive immunity

maternal antibodies

Maternal antibodies decline by

4-6 months baby is vulnurable

Before the antibiotic era _____ immunity with antibody (serum) administration was the only therapeutic option against many bacterial disease 

passive

Passive immunity is _____ dependent

time (better to give before exposure of post exposure but no signs of disease yet)

Standard immunoglobulins indications

Primary humoral immunodeficiencies (example CVID): hep A, measles, varicella, rubella

babies after maternal antibodies have dissipated but before vaccination

Hyperimmunoglobulins indications

antibodies after a person has been vaccinated then given to someone who is not

Anthrax, infant botulism, hep B, CMV, rabies, tetanus, varicella

Animal derived IG (mostly equine) indications 

Envenomation: black widow, scorpion, rattlesnake/cottonmouth

Diphtheria, botulism 

Monoclonal antibodies indications

SARS-CoV-2, RSV, inhalation anthrax

The individual develops their own immune response against a pathogen due to either infection or vaccination

Active immunity

Adjuvants main goal is to

activate and attenuate innate immune response

recruiting in immune cells like dendritic cells to connect to adaptive immune response

Initiation of vaccine response 

Immune mechanisms triggered by vaccines

Antibodies

CD4 t cells

CD8 t cells

Following primary antigen exposure

antibodies are generated

Upon re-exposure to antigen ___ titer of antibodies and _____ presentation

higher; earlier

persist a lot longer

highly avid antibodies (well tailored suit)

Protection is due to induction of antigen specific 

antibodies 

_____ are critical to the induction of high affinity antibodies and immune memory

T cells

Antibodies prevent/reduce infection by

–Neutralizing viral replication by blocking cell adhesion and entry

–Binding to enzymatic active sites or preventing diffusion of toxins

–Promoting opsonization/phagocytosis of bacteria

–Activating complement

Classic methods of generating vaccines 

Live 
Killed 

Toxoid 

Live (attenuated) virus vaccine

1. Isolate virus, grow in cultured human cells

2. Infect non-human cells

3. Virus mutates to grow in non-human cells

4. Attenuated virus no longer grows well in human cells. given back to humans to recognize antigen but not cause disease

Attenuated strains held by CDC/CBER

expanded by vaccine manufacturers

tested for titer and infectivity

Provided alone or in combination with other attenuate viruses (MMR example)

Live attenuated vaccine

Variola

Polio (sabin)

Mumps

Measles

Rubella

Influenza

Varicella (chicken pox)

Varicella (Zoster)

Rotavirus
BCG
Yellow fever

cholera

Inactivated (killed) viral vaccines 

1. Prevailing live strains obtained from CDC/CBER 

2. Monovalent strain incubated with 11 day old embryonated chick egg (or human diploid cell) (single strain)

3. Virus harvested (titer, infectivity, sterility, specificity assessed) 

4.  Virus inactivated by formaldehyde 

5. All inactivated monovalent strains can be combined into single vaccine 

Killed vaccines

Rabies

Polio (Salk)

Pertussis

Influenza (quadrivalent)

Hep A

Japanes

Eneceph

cholera

Toxoid vaccines

Toxogenic bacterial strains

Vat of toxin

Centrifuged and purified

toxin

inactivated with formalyn

toxoid given

Toxoid vaccines 

Diphtheria 

Tetanus 

New platforms of vaccines not RNA/DNA

Subunit PS/protein-polysaccharide

Recombinant protein

Virus like particles

Polysaccharide-protein conjugate vaccine

polysaccharide itself does not activate T cells so no long term

Conjugate with toxoid very potent and immunogenic

Subunit PS Protein-polysaccharide vaccines

Strep pneumo (PS, conj. given to children)

H influenzae Hib (PS, conj)

N meningococcus (PS, conj)

Pertussis 

Typhoid

need exposure to ____ to get memory 

protein 

Recombinant protein vaccines

Hep B

surface antigen into recombinant DNA

extract and purify

very potent 

Recombinant protein vaccines

Hep B

Anthrax

Virus-like particle vaccines

Get rid of genetic material

Virus -like particles

HPV

Rotavirus

Vaccine summary slide

All Six Vaccine Platforms Are Used In The First __ Months Of Life

9 

Vaccines contained weakened or killed disease antigens +

ingredients and byproducts

thimerosol

preservative

sugar and gelatin

stabilizer

aluminum salts 

adjuvants 

Egg/cell proteins

media

Cell culture products

formaldehyde

inactivating ingredients

neomycin

antibiotics

14 Infectious Diseases Mostly Controlled By Vaccines

•Smallpox

•Diptheria

•Tetanus

•Yellow fever

•Polio

•Measles

•Mumps

•Rubella

•Pertussis

•H.influenzae, type b

•Typhoid

•Rotavirus

•Hepatitis B

Important Diseases Caused by Intracellular Organisms are Difficult to Target with Vaccines (antibodies do not enter cells)

Malaria

Mycobacterium tuberculosis

HIV

Burkholderia pseudomallei

Orientia tsutsumagumshi (scrub typhus)