HII: Wk 3 Vaccines Past, Present, Future
What are 2 examples of protein subunit vaccines?
Diphtheria vaccine / tetanus vaccine: formaldehyde-inactivated diptheria toxoid and tetanus toxoid combined with an aluminum phosphate adjuvant Hepatitis B virus vaccine: recombinant HBsAg (virion glycoprotein) combined with aluminum phosphate adjuvant
What is the mechanism of protection of HBV vaccine?
HBsAg-specific antibodies function as: 1. virion "neutralizing antibodies" 2. soluble mediators of RECOGNITION
What was the first vaccine based on a recombinant protein?
Hepatitis B Vaccine Recombinant HBsAg protein expressed in yeasts (add adjuvant)
Why is an adjuvant added to protein subunit vaccines?
Immune system needs inflammatory response initiated to create immunity. Adjuvant is irritating (non-self) so the body will react. Would not otherwise react to just proteins.
Learning objectives 1. Learn the difference between the following types of vaccines and recognize examples of each: (a) live-attenuated vaccine, (b) inactivated vaccine, (c) protein subunit vaccine, (d) conjugated vaccine, (e) virus-like particle vaccine, or (f) DNA-based vaccines. 2. Learn the names, active ingredients, and immunization schedules used to induce protective immunity against bacterial and viral diseases in the U.S. 3. Appreciate the difference between (a) silly arguments against vaccines that are based upon ignorance and misinformation versus (b) the real [but rare] downsides of our current repertoire of vaccines that are based upon clinically measurable observations. 4. Appreciate that the societal utility of vaccines is most appropriately measured in terms of relative risk. Using the DPT vaccine as one example, please read at least 2 clinical case presentations of tetanus, diphtheria, and whooping cough. Compare the consequences of these formerly common diseases to the observed negative consequences of the DPT vaccine in use today. Now weigh the relative risk of the DPT vaccine versus diphtheria, tetanus, etc. and ask yourself whether society would thank us in 50 years for discontinuing the use of the DPT vaccine today. This is the correct approach by which one measures a proposed vaccine's utility or lack thereof. 5. Appreciate that for over a century, it has been widely recognized that clinically useful vaccines must strike an appropriate balance between patient safety and ability of the vaccine to prevent the intended disease (i.e., the safety-efficacy balance). 6. Appreciate that the increasingly litigious nature of medicine has created a regulatory environment in which new vaccines must be "safe," but little heed is given to whether or not these new vaccines are effective. Using herpes and AIDS as representative examples, highly safe DNA- and/or protein-based HSV-2 / HIV vaccines continue to represent the bulk of new vaccine ideas in 2011 despite the failure of similar strategies in clinical trials for >20 years (during which time tens of millions of people contracted genital herpes and AIDS). Although a live-attenuated HSV-2 or HIV vaccine strain might be more effective, and yet still safe, such approaches will not advance to clinical trials unless regulatory agencies reconsider their position on live-attenuated vaccines (i.e., none have been actively developed in the U.S. since the 1960s).
Levinson text: Ch. 12 (p.83-85) & 36 (p.224-228)
What are the 3 types of vaccines?
Live-attenuated microbes Inactivated microbes Protein antigen subunits
The vaccinia virus (cowpox) drove clonal expansion and differentiation of poxvirus-specific lymphocytes. How did this protect against variola virus?
Peopel acquired immunity to vaccinia virus which is cross-protective against variola virus (poxcirus-specific host immune response)
What are 2 examples of live-attenuated vaccines?
Sabin oral polio vaccine: live variants of 3 poliovirus strains (Mahoney type 1, Sabin type 2, Sabin type 3) BCG tuberculosis vaccine: like smallpox approach; animal variant of human pathogen (Mycobacterium bovis) used to inoculate people to elicit cross-protection against human pathogen (Mycobact. tuberculosis).
What are 2 examples of inactivated microbe vaccines?
Salk polio vaccine: formalin-inactivated preparation of 3 poliovirus strains (Mahoney type 1, MEF type 2, and Saukett type 3). Pertussis whole cell vaccine: concentrated Bordetella pertussis cells are inactivated with formaldehyde (P in DTP vaccine).
After Pasteur created the 1st rabies vaccine, what did he coin "vaccination" to mean?
a benign substance that can be injected in a person to (1) elicit an immune response that cross-protects against a disease-causing microbe, and thus (2) prevents disease caused by that microbe
What did "vaccination" originally mean?
• safer (cowpox-based) method of "variolation" • approach to 'acquire' immunity to smallpox
