HISTory/Pharmacy 3708 Vaccines

Louis Pasteur's scientific contributions

* father of microbiology * french national hero - Fermentation and pasteurization - Disproving "spontaneous generation" (Swan Neck Flask Experiment (1859) gems not air leads to fermentation) - discovered that live pathogens treated with heat (attenuation) or passage through another host would stimulate the immune response, without causing disease at all or only a mild disease. - Anthrax and rabies vaccines - he used deceptive practices to overcome his professional rivals

Flu vaccine

- There are over 100 influenza virus strains that have been identified, and they are all slightly different, meaning a vaccine that works for one may not work for another strain. - the influenza virus is an RNA virus, and it mutates easily and often. effectiveness depends on: - characteristics of the person being vaccinated - similarity between the flu viruses and the flu vaccine - may vary by influenza type of subtype even if the viruses are alike - better protection against influenza B or A (H1N1) compared to H3N2

antibodies

- immunoglobulins - glycoproteins that are present in both the blood and tissue fluids - Antibodies are specific to individual epitopes on antigens - antibodies can identify a variety of invaders such as bacteria, viruses and even the toxins released from bacterial or parasitic invaders. - Either a macrophage will be recruited to the pathogen and ingest it and destroy it, natural killer cells will be recruited to the pathogen and destroy it by releasing cytotoxins, or multiple antibody/antigen complexes will agglutinate, or clump together, and be removed by immune cells.

Types of vaccines

- live attenuated - inactivated/killed - toxoid - subunit/conjugate - DNA - mRNA

B cells - T cell independent activation

- occurs when B cell receptors interact with T‐independent antigens - T‐ independent antigens, such as polysaccharides, have repetitive epitope units within their structure, and this repetition allows for the cross‐linkage of multiple B cell receptors, providing the first signal for activation. - B cell undergoes proliferation - become plasma cells - plasma cells create antibodies (IgM molecules) - does not result in a secondary response, short-term protection

B cells - T cell dependent activation

- the resulting immune response is stronger and develops memory - antigen is internalized in the B cell - processed, presented via the MGC II complex - then recognized by a helper T cell that's specific for the same antigen - produces and secretes cytokines - activate the B cell which then prolifirate into memory B cells - and plasma cells that secrete pentameric IgM

routes of administration of vaccines

1. oral - are usually live attenuated vaccines. -OPV, rotavirus 2. parenteral - not GI tract - inhalation - topical -injection (intramuscular - containing adjuvants most of the vaccines: Hep, B, TT,DT, etc subcutaneous - measles, yellow fever, intradermal - BCG- tuberculosis) 3. nasal spray - live attenuated vaccine - some influenza the recommended - the one that limits adverse reactions

Which of the following statements are true about antibodies/antigens?

Antibodies are specific to one antigen Multiple antibodies can exist to identify multiple antigens on one invader Antibodies can provide a signal to macrophages to get rid of the invader

Components of a vaccine

Antigens Stabilizers - sugar and gelatin, which help the active ingredients in vaccines continue to work while the vaccine is made, stored, and moved. Adjuvants - a substance that is formulated as part of a vaccine to enhance its ability to induce protection against infection (alum, Cervarix) Preservatives - protect the vaccine from outside bacteria and fungus (thimerosal - produces ethyl mercury while methyl mercury is harmful) During production: - cell culture material - inactivating ingredients - antibiotics

Antibodies are produced by what cell type?

B cell, plasma cell

Poxviruses

Brick or oval-shaped viruses with large double-stranded DNA genomes. Typically result in the formation of lesions, skin nodules, or disseminated rash. Infection in humans usually occurs due to contact with contaminated animals, people, or materials Ex: smallpox, cowpox etc

William Tebb

British anti-vaccinationist and author of anti-vaccination books. Though not a medical professional, he developed a theory that vaccines were responsible for the spread of leprosy.

DNA viruse

DNA viruses have either single or double stranded DNA as their genetic code and replicate using a DNA‐ dependent DNA polymerase. Usually must enter the host nucleus before they are able to replicate but some replicate their own genome Polyomaviruses, adenoviruses, and herpesviruses smallpox, herpes, and chickenpox

Edward Jenner

Developed a vaccine for smallpox in 1796 - milkmaids -wasn't adopted immediately Dr. Edward Jenner of Gloucestershire, England noticed that milkmaids exposed to cowpox appeared to be immune to smallpox. He tested his hypothesis by inoculating a boy with cowpox pus and subsequently challenging him with smallpox. The experiment was a success, and Jenner prepared a paper describing this case along with 13 other individuals who had contracted either horsepox or cowpox before being exposed to smallpox. - scientific method

Which of the following is not found in sufficient quantities in ANY vaccine?

Formaldehyde

Allan Downie

In 1939, a British researcher, Allan Downie, showed that the smallpox vaccine at the time was inherently different from the cowpox virus. believes vaccinia virus emerged as a mutated form of cowpox in the early years of vaccination

The difference between variolation and vaccination

Inoculation with smallpox: Variolation: refers solely to inoculation with the smallpox virus. Vaccination: refers to inoculation with the cowpox virus.

Jacobson v Massachusetts(1905)

Jacobson - Bostonian pastor who refused to have his children vaccinated because it was an "invasion of his personal liberty."› After being fined by the city, Jacobson sues his case to the Supreme Court. The Supreme Court rules against Jacobson, ruling that states COULD enact compulsory vaccination laws. Larger significance: Most important Supreme Court case concerning the power of the states in public health law.

Anthrax Research

L.Pasteur and R.Koch

Both Immune systems

MONOCYTES macrophages dendritic cells

Cells of the immune system

Macrophages, Helper T Cells, B Cells, Killer T Cells, Memory Cells

What family of DNA viruses does not replicate in the nucleus?

Poxviruses

Cotton Mather

Puritan theologian, who urged the inoculation against smallpox

What was the beaugency lymph?

Pustular material from two areas of France that experienced spontaneous cowpox outbreaks An extremely effective pustular material that was used as the smallpox vaccine throughout the world

What virus family is most prolific?

RNA

Which type of virus is most common?

RNA

the Leicester Method

The Leicester Method involved quarantining anyone suspected of having smallpox and vaccinating suspected contacts. All those working at the quarantine hospital were vaccinated as well as the guards posted on the roads.

Why do you think exposure to cowpox conferred immunity to smallpox in people

The immune system is not very accurate and identifies both cowpox and smallpox as the same virus

Inoculation

The introduction of a pathogen or antigen into a living organism to stimulate the production of antibodies.

What is the main difference between a primary dose and a booster dose?

The primary dose has a higher concentration of antigen compared to a booster dose Most vaccines, such as inactive, subunit or toxoid vaccines do not elicit a very strong immune response. When we use these weaker types of antigens, we have to essentially "remind" our immune system of them multiple times over an extended time to create sustained immunity.

Why was arm to arm transfer of the smallpox vaccine banned?

The vaccine lost its potency this way Other diseases, such as syphilis, were spread this way

RNA viruses

Usually single stranded, may be double stranded (12 families), may be segmented into separate RNA pieces. 34 positive‐sense RNA virus families (covid) exist and 21 negative‐sense RNA virus families high mutation Ebola, SARS, Rabies, common cold, flu, hepatitis C, West Nile fever, polio and measles

Who ultimately determines the composition of the flu vaccine for the U.S. each year?

WHO recommends specific vaccine viruses for inclusion in influenza vaccines, but then each country makes their own decision about which viruses should be included in influenza vaccines licensed in their country. FDA makes the final decision about vaccine viruses for influenza vaccines to be sold in the U.S.

Live attenuated vaccines

Weakened pathogen Closely mimic an actual infection Confers lifelong cellular and humoral immunity - people with weak immune system have a higher risk getting sick - need to be refrigerated measles, mumps and rubella, or MMR vaccine, the chickenpox, or varicella, vaccine, the nasal spray influenza vaccine and the rotavirus vaccine.

Pasteur and Rabies

Who was the first person to be vaccinated for rabies?

viruse

an infective agent that typically consists of a nucleic acid molecule in a protein coat, is too small to be seen by light microscopy, and is able to multiply only within the living cells of a host. Their structure consists of single‐ or double‐stranded DNA or RNA enclosed in a protein coat, making them easier to study and find possible antigens for the immune system to recognize.

William Douglass

anti-innoculation 1721

conjugation in a vaccine

attaching a strong antigen to the weak antigen could elicit a stronger immunological response to the poor antigen involves attaching the polysaccharide to a protein that can activate T cells

MHC

bind antigens and display them on the cell surface for recognition by appropriate T cells. major histocompatibility complex

Toxoid vaccines

chemically or thermally modified toxins used to stimulate active immunity bacterial immune system produces antibodies that lock onto and block the toxin - diphtheria and tetanus are examples of toxoid vaccines.

herd immunity

community immunity if enough people in a community have immunity to a certain disease, they provide protection against the infection for the entire group - vaccine efficacy - vaccination rate

orthopoxes

cowpox, vaccinia, monkeypox, variola 90% of DNA identical or very similar proteins

Inactivated vaccines

dead organisms injected into patient to build immunity - more stable and safer - stimulate a weaker immune system response polio vaccine, hepatitis A vaccine

reverse vaccinology

development of new vaccines using only specific proteins of pathogens that scientists find from the full genome sequence Bexsero, a meningococcal group B vaccine

Attenuation

dilution or weakening of virulence of a microorganism, reducing or abolishing pathogenicity

Helper T cells

drive immune response releases cytokines that then activate the proliferation of B cells, differentiating into memory B cells or plasma cells.

The DNA from DNA viruses must enter the nucleus of the host cell in order to replicate.

false

True or False: Antibodies can only identify bacterial antigens.

false

In what month is the composition of the flu vaccine for the United States decided?

february

Joseph Meister

first person to be administered the rabies vaccine (Pasteur)

Immanuel Pfieffer

he was a local doctor who advertised his abilities to cure "all kinds of chronic diseases by the simple laying on of hands." Vaccines were unnecessary, he claimed. And so off he went to tour Gallop's Island, where smallpox patients were being quarantined. Then he came home and, to perhaps nobody's surprise but his own, he became sick with smallpox. The case became national news, and the New York Times reported that Pfeiffer "probably will die." Anti-vaccination Experiment, Boston (1902)

R naught

herd immunity threshold the basic reproduction number, "reflects how many people each infected person is expected to infect if no one has been vaccinated against the disease" 1-1/R0 - percent of the population needs to be vaccinated

Variolation

inoculation of smallpox into the skin - dried smallpox scabs or pustule fluid into the skin, could still transmit it to other individuals, 1-2% died compared to 30% of a regular smallpox

Lady Mary Montagu

introduced the practice of smallpox inoculation to Europe in 1717 (England) having noticed the effectiveness of this precaution during a stay in Ottoman Empire "Engrafting"

Cetotoxic T cells

kill infected cells CTL

Bacterial vaccines

live attenuated - can be quite reactogenic when made using bacteria because of the many innate toxins and immune stimulators that whole bacteria have (BCG vaccine and the typhoid vaccine) inactive - can also be very reactogenic due to the innate toxins and immune stimulators within the bacteria themselves (not routinely given in the US include a whole cell pertussis vaccine for whooping cough, vaccines against cholera, typhoid and the plague.)

Monocytes

macrophages and dendritic cells key player in the antigen presenting system 1. macrophage ingests the foreign antigen 2. breaks it down 3. presents via MHC (major histocompatibility complex) to a helper T cell 4. T cell becomes activated, produces interleukins - they stimulate other immune cells

Which cell(s) is/are involved in antigen presentation?

macrophages, dendtitic, B cells

vaccines based on the membrane complexes

make small vesicles, or spheres, that have the same outer membrane as the bacteria, but nothing inside, meaning they can't make a person sick.

cells that are derived from myeloid progenitor cells.

make up the innate immune system When the innate immune system is activated, it recruits immune cells to the site of infection, activates cascades to identify invaders and promote clearance of antibody complexes and dead cells, and activates the adaptive immune system

DNA vaccines

nonpathogenic viruses carrying genes for pathogen's antigens utilize a person's own cells to make the antigens of interest - can't cause the disease - shoot microscopic gold particles coated with DNA directly into cell

macrophages and dendritic cells

not a huge difference between dendritic cells and macrophages. They are mainly differentiated by different cell surface markers.

cells that derive from lymphoid stem cells

part of the adaptive immune system -T cells (cytotoxic, helper) -B cells (plasma and memory) creates immunological memory after an initial response to a specific pathogen and leads to an enhanced response to subsequent encounters with that pathogen

Retrovirus

postitive-sense RNA virus with a DNA intermediate the virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome. the host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the cell's own genes HIV and hepatitis B

which type of DNA virus does not reproduce in the nucleus of the host cell

poxviruses

Peter Razzell

proposed that vaccinia virus was actually an attenuated form of variola virus.

interleukins

proteins that stimulate the growth of B and T lymphocytes The immune system also uses a complex system of signals that involve secreted proteins known as interleukins. are synthesized by helper T cells as well as through monocytes, macrophages and endothelial cells

polysaccharide bacterial vaccines

similar to subunit These vaccines are composed of long chains of sugar molecules that make up the surface capsule of certain bacteria. Stimulate T cell indep. immunity; stimulate B cells without the assistance of T-helper cells, short-lived immunity; no booster effect current conjugated polysaccharide vaccines include vaccines against pneumococcal disease, the Hib vaccine, and meningococcal vaccines.

combination vaccines

simultaneous administration of antigens from several pathogens

Bacteria

single‐celled prokaryotes, and tend to live in microbial communities more complex, single-celled, harder to create a vaccine

lancet

small surgical tool for making incisions (innoculation)

Spontaneous Generation

the mistaken idea that living things arise from nonliving sources. cell biology debunked the theory Rudolf Virchow (1821-1902): Omnis cellula e cellula ("All cells come from cells")

subunit vaccines

use antigenic fragments to stimulate an immune response sometimes use epitopes - lower chances of adverse reaction - recombinant subunit vaccines pneumococcal and meningococcal vaccines, and vaccines for HPV, Hib, pertussis, and shingles

mRNA vaccines

we go straight to mRNA for the desired proteins/antigens, and inject that into the body - translate into a specific protein/antigen

The UK Vaccination Acts of 1840, 1853, 1867 and 1898

1840: variolation illegal, provided optional vaccination free of charge. 1840s: state-sponsored vaccination campaigns begin in England and Germany, and a noticeable reduction in cases of smallpox results. 1853: British Parliament mandates compulsory vaccination (The Vaccination Act) "That every child, whose health permits, shall be vaccinated within three, or in case of orphanage within four months of birth, by the public vaccinator of the district, or by some other medical practitioner." 1867 Vaccination Act: Poor-law guardians were to control vaccination in parishes, and pay vaccinators from 1s to 3s per child vaccinated in the district -Within seven days of the birth of a child being registered, the registrar was to deliver a notice of vaccination; if the child was not presented to be vaccinated within three months, or brought for inspection afterwards, the parents or guardians were liable to a summary conviction and fine of 20s. -Any person who produced or attempted to inoculate another with smallpox could be imprisoned for a month. 898 Vaccination Act: -Allowed conditional exemption for conscientious objectors -Removed cumulative penalties for non-vaccination -Introduced a conscience clause, allowing parents who did not believe vaccination was efficacious or safe to obtain a certificate of exemption. 1907 Vaccination Act: -Parents would not be penalized for non-vaccination of their children if the parent made a statutory declaration that he confidently believed that vaccination would be detrimental to the health of the child, and within seven days thereafter delivered, or sent by post, the declaration to the Vaccination Officer of the district.

a foreign antigen

A foreign antigen is technically a substance that induces an immune response, so it could be a virus, bacteria, allergen, parasite or other substance.

mono and polyvalent vaccines

A monovalent vaccine contains a single strain of a single antigen, whereas a polyvalent vaccine contains two or more strains/serotypes of the same antigen. flu protects against several strains