Vaccines and Immunity Intro

Variolation

small amounts of a virus given to a healthy person

Result of variolation

mild form of the illness and decreased mortality

Variolation in the Americas by

Onesimus

Variolation in Europe

Lady Mary Montagu

Edward Jenner

cowpox and milk maids; innoculated his family and friends

Vaccine life cycle

basic research, discovery, pre clin studies, IND, Phase 1 (Safety), Phase 2 (effectiveness), Phase 3 (safety and effectiveness), BLA, FDA Review, FDA approval, ACIP Review, ACIP recommendation, psot surveillance

Immune memory is sufficient when

incubation period is long

Immune memory may not be sufficient against

rapidly invasive pathogens which means you need boosters

Types of vaccines

live attenuated (weakened or inactivated), killed whole organisms, toxiod, sub unit, virus like particles, outer membrane vesicles, protein polysaccharides conjugate, viral vectored, nucleic acid vaccine

Attenuation

reduces virulence while maintaining immunogenecity

common methods of attenuation

pass through a natural host, grow on unusual media, exposure to harsh chemicals

Rational attenuation

MMR, chicken pox, and zoster

pros of live attenuated

• body does not differentiate between wild-type and attenuated microbe

• 1 vax

• elicts a vigourous long lasting immune response

• replicates sufficient to produce a strong immune response

cons of live attenuated

-virus can mutate and revert back to being virulent

-live attenuated virus can be shed by respiratory route (risk to the immunosuppressed)

Killed whole organism

whole organism is killed by physical or chemical means

example of killed whole organism vax

salk polio

pro of killed whole organism vax

-does not revert back to the virulent state

-poses little health risk to the immunosuppressed

cons of killed whole organisms

• weakly immunogenic

• need a booster

Toxid vaccines

-modified bacteria endotoxins

-antibodies directed at toxid neutralize exotoxins before they can reach the target cell

example of a toxid vaccine

tetanus

pro of a toxid vaccine

non-pathogenic

con of a toxid vaccine

requires large doses to enduce a immune response

why are antibodies effective at neutralizing exotoxins

• t cells recognize linear epitopes of antigens

• antibodies recognize the liner epitopes and conformational epitopes

• they can recognize secondary, teritary, and quartenary proteins and glycosylated proteins

subunit vaccine

-antigenic molecules or citical epitopes necessary for protection against infection

whole cell vaccines have what

non antigenic molecules which can cause rare systemic and local effects

example of a subunit vax is

DPT

pros of a subunit vaccine are

does not cause infections and pose little risk to immunocompromised individuals

virus like particles

particles constructed of viral proteins that structures mimic the native virus but lack the viral genome (Nonenveloped VPLs and Enveloped VPLs)

ex of a virus like particle vaccine

gardasil

pro of a virus like particle vaccine

non infectious

con of a virus like particle vaccine

-less immunogenic

-challenges with production and stability

Outer membrane vesicle vax

-contains gram negative bacteria outer membrane and antigen

-generated through vesticulation: spontaneous, mechanical disruption, detergent extraction, genetic manipulation

-contains PMPs and activated TLRs

outer membrane vesicle vaccine example

group B meningococcal

outer membrane vesicle vaccine pros

-versatille antigen delivery

-elicts broad immune response

cons outer membrane vesicle vaccine

-potentially tox LPs

-low yield

polysaccharide and protein polysaccharide conjugated vaccines

-contains major virulence factors for pneumococcus and Pseudomonas

-need to be conjugated to proteins to elicit a t cell dependent response and the generation of immune memory

polysaccharide and protein polysaccharide conjugated vaccine con

limited usefulness

Viral vectored vaccine

recombinant virus with altered genomes to express the target pathogen antigen

example of viral vectored vaccine

astrazenca

pro of viral vectored vaccine

mimics natural inflection to induce strong humoral and cellular immune responses without the need for adjuvant

con of viral vectored vaccine

pre existing immunity to vectors that commonly cause infections in humans

Nucleic acid vaccine

consist of either DNA ro RNA encoding the target antigen

Nucleic acid vaccine example

moderna covid-19

pro of nucleic acid vaccine

highly versatile

con of nucleic acid vaccine

-lack of stability

-low transfection rate and limited immunogenecity

-need to be delivered directly into cells which require specific injection devices

what are two ways interferons help to fight viruses?

-activate nucleases that cleave RNA

-Inhibit viral protein synthesis by down regulating elongation factors

T/F: A booster is given to increase antibodies to protective levels when a pathogen is rapidly invasive

true

what is rational atteunation?

Inactivation or removal of virulence genes by targeted mutation or deletion

Measles Immune Evasion

Viral V: directly binds MDA5 and LGP2 and inhibits IFN synthesis and JAKSTAT signaling

Viral C: interferes with IFN transcription

Viral P: inhibits IFN

Immune Amnesia of Measles

-acute phase: Measles= suppression

-Measles paradowx= can lead to opportunitic infection for weeks to months after infection

Subcutaneous or intramuscular

-stimulate systemic immunity= spleen and lymph nodes and peripheral blood

-stops person to person transmission

-spreads to important organs

Mucosal administration

antigen stimulates lymphocytes from initial site travel to other mucosal surfaces conferring immunity at multiple mucosal sites

-prevents infection in important organs

-easy to administer

-oral and nasal

Oral administration

antibody response in small intestine, ascending colon, and mamammary and salivary glands

Nasal administration

protects the upper airways and lungs

passive protection

-mom to baby

-use of specific neutralizing antibodies purified from immune donors to prevent transmission of various viruses

herd immunity

-infection cannot spread throughout population

-susceptiable individual are indirectly protected by vaccine individual

Major complications of measles

-immune suppression increase susceptibility to intestinal and respiratory infections

-encephalitis

-subacute sclerosing panecephalitis= rare and progressive deterioration of CNS

MMR vaccine

• live attenuating vaccine and combo with mumps and rubella

• produces a mind, noncommunicable infection

• life long immunity

R=

basic reproduction number

R0 for measles

12-18

means 1 person can infect 12-18 people

what does r0 determine

herd immunity threshold

how is measles transmitted

inhalation

Incubation of measles

10 days fever and 14 days rash

measles

-single stranded, negative sense RNA paramyovirus

-cell receptors utilized for entry: SLAM, nectin 4, DC SIGN, langerin