IE 3: Vaccines 2 Totonchy

Explain herd immunity and the relationship between vaccine efficacy and the epidemiology of a pathogen?

• Herd immunity is achieved when enough of a population is immune to limit the spread of the pathogen

• Take into account 3 things: 1) how contagious the pathogen is (more contagious = higher threshold for herd immunity); 2) vaccine effectiveness; 3) percent of the population that is vaccinated

• Ex: with an R0 of 2 you need 50% (1-1/R0) community immunity to achieve herd immunity which means vaccine effectiveness x percent uptake >0.5

Identify what component of a given vaccine formulation has adjuvant activity (remember innate immune activation/pattern recognition).

• Every vaccine has something that activates innate immunity. For live attenuated vaccines, the PAMPS are built in

• Similarly for mRNA vaccines because RNA itself can activate pattern recognition, and viral vectored vaccines the virus vector and vaccine DNA can activate pattern recognition

• However some inactivate and protein subunit vaccines need dedicated adjuvants in order to get an optimal immune response

Determine based on a vaccine formulation whether antibody only or antibody + CTL responses can be expected. (remember antigen presentation)

• The best way to reason this out is asking yourself where the vaccine antigens are once they’re in the body

• If they’re outside cells (like a protein subunit or whole inactivated vaccine) then you probably won’t get CTL response

• If the antigens are made inside cells in the vaccine recipient (like with live attenuated, viral vectored or mRNA/DNA) then a CTL response is more likely to happen

List the advantages and disadvantages of vaccine strategies that require antigen selection vs whole microbe approaches.

• Whole microbe approaches are necessary when we don’t have enough info about how the immune system will best target the pathogen (ex: we don’t know which antigens to use for a targeted strategy)

• If we DO have info about which antigen is best to target, subunit and molecular approaches are generally safer for a greater proportion of the population than a live attenuated approach, and are generally more effective than whole inactivated approaches

Explain the relationship between vaccine durability and pathogen mutation rate and how this may be influenced by antigen target selection.

• Pathogens can mutate to evade immune responses in some cases and generally the more mutation that happens the more likely this is to occur

• Whole microbe vaccine approaches are less susceptible to this bc they generate responses that target multiple parts of a pathogen. However good antigen selection can minimize this issue for subunit vaccines if an antigen can be found that is critical for the function of the pathogen so the ability of the pathogen to mutate that target is limited

Compare the development and formulation of genetic vs protein based vaccination strategies.

• Protein subunit vaccines can be slow and laborious to make bc we have to make the protein in lab but we need structural info to get it to “look” right to get the optimal immune response that will work against the real thing

• Molecular strategies like mRNA/DNA/viral vectored get around thus by using the expertise of cells to make the protein inside the vaccine recipient. The only info needed is the genetic sequence that encodes the protein which speeds up development