Vaccines Flashcards

1
Q

Origin of vaccines

A

smallpox, vaccination with cowpox, Edward Jenner 1796, eradicated 1980

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2
Q

Vaccines and immune prophylaxis

A

Various strategies to induce immunity prior to pathogen exposure, by passive or active immunization, by natural processes (transplacental transfer of maternal IgG or prior infection) or by artificial means (injection of antibodies or vaccines).

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3
Q

Childhood immunization schedule in nova scotia

A

DTaP-IPV-Hib - 2 months, 4 months, 6 months, 18 months. Pneumo Conj - 2 months, 4 months, 12 months. Men C Conj - 12 months. MMRV - 12 months, 18 months, 4-6 year. Tdap-IPV - 4-6 years. Tdap, meningococcus, HPV, Hep B - 12 years.

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4
Q

Passive immunization

A

the administration of preformed antibody in order to give temporary protection against infection. Antibodies of maternal origin provide the newborn with a measure of protective systemic and local immunity. Pooled γ-globulin from horses immunized deliberately or humans immunized can be used to provide emergency protection for human beings when time does not allow for the development of adequate protection by active immunization. There is one approved monoclonal antibody on the market for passive immunization (Synagis®, palivizumab - used to prevent RSV infection in very premature babies).

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5
Q

Risks of passive immunization

A

Repeated administration of γ-globulin from foreign species can cause systemic anaphylaxis (Type I hypersensitivity) if IgE is made against the foreign protein. Human γ-globulin can trigger an anti-allotypic antibody response resulting in Type I or Type III hypersensitivity.

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6
Q

Active immunization

A

The aim of active immunization is to generate protective immunity and immunologic memory so that a subsequent exposure to the pathogen will stimulate a vigorous immune response leading to elimination of the pathogen. Active immunization can be achieved by natural infection or by vaccination. Not 100% effective.

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7
Q

Herd immunity

A

Indirect protection from infectious disease due to a large percent of the population becoming immune to infection. Essential to protect members of the population that cannot be vaccinated → newborns, pregnant or breast-feeding women, immune compromised.

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8
Q

How do vaccines work

A

Administration of antigenic material (biologic) to stimulate an individual’s adaptive immune response to a pathogen (without development of disease, memory immune response). Induction of B cell/humoral immune response (cytotoxic T cells can kill infected cells, prevent spread of infection).

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9
Q

What is an antigen

A

Any substance capable under appropriate conditions, of inducing a specific immune response and reacting with the products of that response; that is, with specific antibody or specifically sensitized T lymphocytes, or both.

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10
Q

The goal of a good vaccine

A

The objective of vaccination is to establish adequate levels of immune responses to protect against infectious agents. If the incubation period is short, it is important to maintain high levels of antibody by repeated immunizations since in such cases an infection could become established before memory B cells would be able to produce enough antibodies to have a protective effect. Antigens used as the basis for vaccine development must be readily available, stable, cheap and safe. The site of the immune response to the vaccine is important.

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11
Q

Examples of vaccine antigens

A

Poliovirus vaccines must contain T and B cell epitopes to generate humoral immunity (secretory IgA) against poliovirus (needs to be active in the gut, that is where it replicates). Only Th1 cells need to be activated in order to generate a protective DTH response against tuberculosis bacilli. To induce a protective immune response against measles virus, the pathogen must be allowed to undergo limited replication in host cells in order for viral antigen t

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12
Q

Live related vaccines

A

immunize with a closely related but much less pathogenic organism. Count on immunologic cross-reaction in response. Ex: cowpox (vaccinia) prevents smallpox (Jenner) - ”vaccinate”; leishmania major (skin) vs. leishmania donovani (viscera) - leishmanize. Positives: very strong protection, persistent antigen source, lots of antigens. Negatives: risk of serious infection, lack of availability of non pathogenic relatives to common pathogens.

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13
Q

Live attenuated vaccines

A

Concept: weak pathogenicity and growth ability (attenuate) of pathogen to allow for activation of immune response but not disease; attenuation achieved through chemical treatment, radiation or molecular manipulation. Ex: MMRV, flumist, oral polio (Sabin). Positives: persistence, full spectrum of antigens, humoral and cell mediated immunity, long lasting protection (limited boosting required). Negatives: risk of disease, care to not give to immunodeficient patients, require careful storage and handling.

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14
Q

Inactivated vaccines

A

Consist of microbes that are killed by heat or chemical treatment and are therefore unable to replicate but maintain their antigenic constitution and immunogenicity. Split virus: pathogen particles are inactiavted then disrupted with detergent or ether (reduces irritation). Ex: IPV (Salk), seasonal flu. Positives: very safe, wide spectrum of antigens. Negatives: no persistence, limited cell mediated immunity, often need adjuvant, boosting required, antigens damaged by treatment used to kill pathogen. Incomplete inactivation of the pathogen may lead to disease.

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15
Q

Sub unit vaccines

A

Isolated protein or recombinant protein derived from pathogen, often delivered with adjuvant commonly alum. Ex: Tdap/DTaP (diptheria, tetanus, pertussis), seasonal flu. Positives: very safe, easily transported and stored, used for organisms that produce potentially fatal toxins. Negatives: weak immunogen, needs adjuvant, needs boosting, no spectrum of antigens, transient (no persistence).

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16
Q

Polysaccharide conjugate vaccines

A

Link polysaccharide to protein for T depedent antibody production, T cells are activated by peptide, not polysaccjaride, used for organisms that hvae surface polysaccharide coat.s

17
Q

Virus like particle vaccines

A

Multiprotein structures that mimic the organinzation and conformation of authentic native viruses but lack the viral genome. Ex: HPV, Hep B
Positives: safe, spectrum of antigens for cell mediated and humoral immunity, quick manufacturing
Negatives: requires virus genome to be sequenced, complex manufacturing/purification, immunogenicity may vary depending on culture conditions, may require adjuvant, not persistant

18
Q

Challenges to developing new vaccines

A

More significant challenges: respiratory syncytial virus (RSV), malaria, HIV. With increased understanding of immune system, new vaccines. Shift from empirical to rational design.

19
Q

Novel vaccine technologies

A

Driven by two vaccine requirements; safety and efficacy. Antigen (increasing adjuvant/formulation): whole organism → toxin/toxoid → protein → epitope.

20
Q

Adjuvants

A

A substance that enhances the immunogenicity of an antigen - stimulate innate immune recognition of antigen. Molecular defined structures that mimic PAMPs or DAMPs and stimulate the innate immune system PRRs - CpG (TLR9 ligand), poly I:C (TLR3 ligand). Alternatively can be an oil/liposome which prolongs stability and interactions of antigens with the immune system - e.g. Freud’s complete adjuvant.

21
Q

DNA vaccines

A

DNA vaccines are based on plasmid DNA that encodes antigenic proteins. DIrect injection of the plasmid DNA (sometimes coated on microscopic gold beads) into the muscle of the recipient causes the proteins to be expressed by muscle cells and adjacent dendritic cells. DNA vaccines induce humoral and cell-mediated immunity that is long-lasting due to prolonged expression of the antigens. DNA vaccines are a good option in a pandemic situation because they are very quick to make. Same with mRNA vaccines.

22
Q

Viral vectored vaccines

A

recombinant vector vaccines are produced by inserting genes coding for the major antigens of a pathogen into attenuated viruses or bacteria. Vaccinia virus is a popular vector due to its history of safety. Other non-pathogenic viruses can also be used (VSV for the development of an Ebola vaccine)

23
Q

Peptide-based vaccines

A

Using the smallest, synthetic epitope available to generate an immune response - for T cell epitopes, minimal is ~9-10 amino acids. Vaccine adjuvants and formulations are very important. Highest level of safety due to small synthetic nature. Common in newer vaccines that target T cell responses.

24
Q

What are cancer vaccines?

A

There are two types: 1) Prophylactic (prevent cancer) - usually against infections that have been shown to cause cancer; ex: Guardasil (HPV). 2) Therapeutic (fight cancer) - target the cancer after after you have been diagnosed and treated. Idea: when the tumor is at its most vulnerable (ie. after surgery and chemo) treat with a vaccine to stimulate the immune system to keep the tumor in remission. Hep B has been shown to increase the risk of liver cancer significantly - vaccinating against Hep B can prevent against liver cancer.