10: Viral Vaccine Strategies Flashcards
What are the 2 different types of vaccination?
What are the aims of viral vaccination?
What 3 forms were ‘old’ vaccines given in?
Prophylactic (development of immunity in susceptible host); theraputic (to augment/induce effective immunity in those previously infected)
Prevent/modify viral disease. Induce protective/durable immune response. Protective against different strains. Eradication (e.g. smallpox)
Live, attenuated (weakened virus replicates sufficiently in host to induce protective immune response without causing disease e.g MMR, adenovirus, smallpox.) Inactivated whole virus. Subunit (viral fragment).
What is MMR?
In a live attenuated virus vaccine, what are the:
a) methods of attenuation?
b) mechanisms of attenuation?
Measles (serious childhood infection, encephalitis, blind/deafness), mumps (commonest cause of viral encephalitis, deafness, sterility), rubella (infection of a mother early in pregnancy can cause foetal deal or CRS).
a) repeated passage in a diff host/through cold, reassortment with attenuated genes
b) receptor interaction with host cell, gene expression and replication, virion maturation.
What are some advantages and disadvantages of live attenuated virus vaccines e.g. MMR?
Advantages: stimulates a broad immune response (neutralising Ab, secretory IgA for mucosal tissues, cell mediated immunity), all antigens are expressed, production costs lower.
Disadvantages: potential for genetic instability and contamination, infection can persist or be more severe in the immuno compromised. E.g circulating vaccine-derived poliovirus due to un or under-immunised population.
What are inactivated whole virus vaccines?
List some advantages and disadvantages of them.
Large batches of live virus inactivated by treatment with formalin or beta-propriolactone e.g hep A, influenza
Advantages: little infection risk, multiple surface proteins present (important when protective antigens are numerous or unknown)
Disadvantages: handling large volumes of virulent virus, risk of incomplete inactivation, parenteral administration, virus derived in culture and inactivated may not mimic forms generated during natural infection; poor immunity or potentiate disease upon subsequent infection. Immunity often brief, requiring boosting; toxicity associated with repeated exposure to foreign proteins.
What are subunit vaccines?
What are virus-like particles?
What are the advantages and disadvantages of both?
Highly purified subviral components needed to stimulate protective immune response (i.e. surface glycoproteins). E.g. hep B
Virus proteins self-assemble into a particle. Non-replicating, self-assembling, ordered structure and highly immunogenic. E.g. HPV
Advantages: little infection risk, least toxic, viable approach when no cell culture system available e.g. HBC or significant biohazard (HIV)
Disadvantages: often less immunogenic or of an appropriate type (dominant Th-2 cell response, IgG Ab response predominantly not complement-fixing, no CTL response). Multi-step purification can be costly and difficult (protein may lose immunogenic epitopes, v large quantites may be needed, host cell protein and DNA must be removed).
What is herd immunity?
What percentage of individuals in a population need to be immunised to achieve herd immunity?
How is the herd immunity threshold calculated?
Indirect protection from infection of susceptible members of the population, and the protection of the population as a whole, which is brought about by the presence of immune individuals.
Varies and depends on factors like effectiveness of vaccine and disease characteristics. For non-infectious diseases e.g. tetanus there is no herd immunity.
H = 1 - 1 / R0
R0 is the critical proportion susceptible (epidemic threshold), where R = average number of transmissions per case. R_EPRODUCTION FACTOR_
Why is herd immunity important?
List some techniques for vaccine development.
List some infectious diseases that have no current vaccine,
The most effective way of protecting people who don’t respond to vaccines or can’t be given them for medical reasons.
Empirical approach, recombinant DNA, glycoconjugation, reverse vaccinology, next-generation technologies. Synthetic vaccine e.g. polio. Recombinant vectors e.g. ebola. Attenuated vaccines: microRNA, codon de-optimisation, reverse genetics. Inactivated vaccines: DNA plasmids and shuffling, fusion proteins, innate immunity induction.
Ebola, enterovirus 71, hantavirus, lassa, marburg, SARS, dengue, human monkeypox.
Universal influenza vaccine possiblity?
List some live attenuated virus vaccines.
List some inactivated whole virus vaccines.
List some subunit virus vaccines.
Name a virus-like particle vaccine.
Rotavirus, varicella, MMR, polio-sabin, adenovirus, yellow fever, small pox
Polio-salk, influenza, hep A, rabies, japanese encephalitis
Hep B, tick borne encephalitis
HPV
