Flashcards in Anti-Virals Deck (25)
What is the goal of viral vaccines?
Goal is prevention of disease and limiting of transmission via “herd immunity”
What is the importance of immunogenicity?
Immunogenicity is based on laboratory measurement of antibody responses
- Proportion of recipients who develop antibody
- Antibody levels (titers)
How do we define the efficacy of a vaccine?
Based on ability of vaccine to protect against disease
- Measured by clinical trials and case-control studies
What are the most frequent adverse effects to vaccines?
- Local reactions
- Immediate reactions => Syncope and Hypersensitivity reactions
What are the most severe (and rare) reactions to vaccines?
- Fever => Febrile seizures
- Disease due to live vaccine virus
- Neurological disease => Guillan Barre
- Immune mediated –atypical - disease
What are the relative contraindications for LIVE vaccines?
What are relative contraindications for vaccines (general)?
- Allergy to a Vaccine Component (ie eggs)
- Previous Reactions to Vaccine
For the most part, what part of the immune response do vaccines rely upon?
Adaptive immunity => generally cell-mediated
What are the main characteristics of live vaccines?
1) Immune response depends on replication of the live agent or the vector expressing viral proteins
2) Induces broad immune response
3) Often requires only 1 or 2 doses for complete or long term immunity response depends on vaccine “take”
4) Do not contain adjuvants/preservatives but may be sensitive to thermal conditions
What are the primary LIVE vaccines available?
-Oral polio virus vaccine (OPV)
-Rotavirus vaccine (PRV, HRV)
-Measles, mumps, rubella vaccine (MMR)
-Varicella-zoster virus vaccines (VZV,ZV)
-Live, attenuated influenza vaccine (LAIV)
-Yellow fever vaccine (YFV)
-Experimental (RSV, PIV, Ebola, Dengue)
What are the main characteristics of INACTIVATED vaccines?
- Immune response generally limited to serum antibody production
- 2-3+ doses required for full protection against disease, amnestic response.
- Response may be less durable
- May contain preservatives and/or adjuvants
What are the approaches to formulating INACTIVATED vaccines?
- Inactivated whole organism
- Subunit vaccine/recombinant antigens
- Non-replicating vectors => conjugating polysaccharides to protein carriers (can be very immunogenic)
What are the main INACTIVATED vaccines?
- Inactivated poliovirus vaccine (IPV, Salk)
- Influenza vaccine (TIV)
- Hepatitis B vaccine (HBV)
- Human Papillomavirus vaccine (HPV)
- Experimental (EBOLA, HIV, Hepatitis E, RSV)
What are various reasons antiviral treatments may be given?
- Withdrawal of immunosuppressive therapy
- Protection from exposure (i.e. influenza)
- Prophylaxis of an at risk individual
- Immune globulins (IVIG, vaccinia immune globulin, CMV IG)
- Human Rabies Immune Globulin (HRIG)
What are various methods of inducing passive immunity?
- Animal serum
- Standard human immune serum globulin
- Special Intravenous Immune Serum Globulins ( ie HEP, varicella, rabies, CMV...)
What is the target for herpes viral drugs?
Viral thymidine kinase
- Acyclovir, valacyclovir, famicyclovir
What are the primary routes of administration of Acyclovir?
- IV and oral
What are the indications for Acyclovir?
- HSV (orolabial, genital, encephalitis, immunocompromised, and neonatal infection--TORCH)
- Varicella Zoster
What are the main types of influenza antivirals?
1) Neuraminidase inhibitors
2) M2 channel blockers
3) Inhibitors of host cell protease responsible for hemaglutinin cleavage
What are the primary neuraminidase inhibitors?
2) Oseltamivir (Tamiflu)
What is the mechanism of action of neuraminidase inhibitors?
- NIs are effective against => influenza type A and influenza type B.
- NI drugs selectively inhibit neuraminidase, a viral envelope glycoprotein that facilitates penetration through thick respiratory tract mucus secretions
- Neuraminidase is also necessary for the optimal release of newly formed virus from infected cells
- Neuraminidase inhibition causes uncleaved sialic acid residues to collect on the surface of host cells. Viral hemagglutinin in the viral envelope binds to the uncleaved sialic acid residues, resulting in viral aggregation and a REDUCTION in the amount of virus that is released to infect other cells, a process referred to as viral shedding.
What drugs are used as prophylaxis (60-70%) and treatment for influenza?
- Zanamivir and Oseltamivir
What is the mechanism of action of M2 blockers (amantadine)?
The mechanism of amantadine's antiviral activity involves interference with the viral protein, M2, a proton channel.
Why is amantadine no longer used?
all current influenza strains are resistant to amantadine