How to Spot a Virus. The origins of an immune response. Kevin Bonham Sky Brubaker Jillian Astarita

Transcription

1 How to Spot a Virus The origins of an immune response Kevin Bonham Sky Brubaker Jillian Astarita

2 Quick recap Many types of pathogens exist Immune cells have different receptors to see these pathogens Innate immune cells instruct adaptive immune cells Different immune responses are required to effectively kill different pathogens

3 How can we instruct the immune system to make better vaccines? History lesson: how did scientists develop vaccines? Why old methods don t work for all pathogens What we need to learn to make them better New techniques/promising clinical trials

4 A brief history of vaccination Edward Jenner infects 8 yr old boy with cowpox and confers smallpox protection Son of a Chinese statesman inhaled dried smallpox scabs to confer protection Thehistoryofvaccines.org

5 These vaccines worked but scientists didn t know how Inject (not very harmful) pathogen?? Long-term (10-50 years) immunity

6 A brief history of vaccination Edward Jenner infects 8 yr old boy with cowpox and confers smallpox protection 1796 Louis Pasteur discovers that repeatedly infecting chickens with cholera weakens the pathogen Son of a Chinese statesman inhaled dried smallpox scabs to confer protection MA passes first U.S. law mandating vaccination for school children 1855 Thehistoryofvaccines.org

7 These vaccines worked and scientists were starting to figure out how Inject Inject (not very weakened harmful) pathogen?? Long-term (10-50 years) immunity

8 A brief history of vaccination Edward Jenner infects 8 yr old boy with cowpox and confers smallpox protection 1796 Louis Pasteur discovers that repeated passes through chickens weakens cholera Son of a Chinese statesman inhaled dried smallpox scabs to confer protection 1855 MA passes first U.S. law mandating vaccination for school children 1890 Serum therapy for diptheria discovered by Kitasato and von Berhing Thehistoryofvaccines.org

9 These vaccines worked and scientists were starting to figure out how Inject weakened pathogen Generation of protective antitoxins (antibodies)?? Long-term (10-50 years) immunity Inject protein from a pathogen (antigen)? No effect!

10 A brief history of vaccination Edward Jenner infects 8 yr old boy with cowpox and confers smallpox protection 1796 Louis Pasteur discovers that repeated passes through chickens weakens cholera 1879 A. T. Glenny first used alum in diptheria vaccine to increase effectiveness Son of a Chinese statesman inhaled dried smallpox scabs to confer protection MA passes first U.S. law mandating vaccination for school children Serum therapy for diptheria discovered by Kitasato and von Berhing Jonas Salk develops polio vaccine; approved for humans in 1955 Thehistoryofvaccines.org

11 These vaccines worked and scientists figured out how! Inject weakened pathogen or Inject protein from a pathogen (antigen) + an adjuvant Immune cells see pathogen through innate receptors,? instruct adaptive cells Generation of protective antitoxins (antibodies) Long-term (10-50 years) immunity

12 Problems with the old methods Don t work for every pathogen Largely result in antibodies Sometimes need different responses

13 Limitations of antibody protection Influenza binding sites HIV binding sites Flu HIV

14 What do we need to learn to make better vaccines? 1. What type of immune response will be most effective? 2. Which pattern recognition receptors should be targeted? 3. Which cells should antigen and adjuvants be delivered to?

15 1. What type of immune response will Bacteria be most effective? Receptor Nucleus Virus Cytoplasm

16 Dendritic cells are specialized phagocytes Dendritic cell Dendritic cells are very good at: Seeing pathogens through pattern recognition receptors Deciding what type of immune response should occur Instructing other immune cells

17 2. Which receptors should an adjuvant target? Cytokines released Type of immune response Dendritic cell

18 3. Which dendritic cells should be targeted?

19 Recent advances in vaccines Directly targeting antigens to dendritic cells Collecting dendritic cells and modulating them outside the body

20 There are many types of dendritic cells in different areas of the body Small intestine

21 Old vaccine technology provides full body protection vaccine??? K

22 Vaccines can be targeted to specific dendritic cells

23 Recent advances in targeted antigen delivery Directly targeting pathogenic antigens to dendritic cells Collecting dendritic cells and modulating them outside the body

24 Cancer and the immune system Current cancer treatments (chemotherapy) are nonspecific and very harmful to healthy cells Immune system can fight cancer cells But, it is hard to see them because they look similar to our own cells in many ways We can use vaccine technology to help the immune system

25 Preventative vaccines vs. Treatment vaccines

26 Dendritic cells can be removed from the body and educated to recognize antigens Cancer antigens Cytokines Inject DCs back into patient Blood collected from patient Grow large numbers of dendritic cells

27 Dendritic cells therapy has some drawbacks Costly and time consuming Need more knowledge of cancer antigens Need more knowledge about how to best train dendritic cells

28 but shows great promise for several diseases Has been largely safe for patients Prostate cancer - first FDA-approved cancer vaccine for men with metastatic prostate cancer Melanoma HIV

29 Summary of part 3 Many successful vaccines confer protection through antibodies For some diseases, different types of protective responses are needed Scientists need to learn more about immune responses to make better vaccines

30 How to spot a virus: take home messages There are many different types of pathogens the immune system needs to see and defend the body against The immune system needs to direct an appropriate response against different pathogens Understanding how to direct these responses will allow us to make better vaccines

31 Thank you! SITN would like to acknowledge the following organizations for their generous support. Harvard Medical School Office of Communications and External Relations Division of Medical Sciences The Harvard Graduate School of Arts and Sciences (GSAS) The Harvard Biomedical Graduate Students Organization (BGSO) The Harvard/MIT COOP Restaurant Associates