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Presented at a lecture for Clinical Research Coordinators held at King Fahad Medical City, Riyadh on Thursday, July 08, 2020 at 1:00-2:00. By: Professor Omar Hasan Kasule Sr. MB ChB (MUK), MPH (Harvard), DrPH (Harvard) Chairman of the Institutional Review Board
INTRODUCTION:
INTRODUCTION, con’t.· Vaccination is the process of inoculation that produces immunization. Antigen is a component of the bacterium or virus against which an antibody is formed.
· In 1954, the Salk inactivated polio vaccine was tried in a field trial. In the 1960s Dr Sabin developed a weakened (attenuated vaccine) called the Oral Polio Vaccine (OPV) that is given orally and is the one used now. OPV gives better immunity but being a live vaccine can revert to the wild form and cause disease in children – a few un a million.
STAGES OF VACCINE DEVELOPMENT: Pre-clinical phase in the lab and animals· In the 1918, Spanish flu that killed 100m the only remedy was transfusion of blood from recovered patients.
· Starting in 1931, the influenza virus was grown in embryonated eggs and in the 1940s inactivated vaccine was developed. In 2012 vaccines made from cell cultures were approved and later vaccines were made using recombinant DNA techniques.
· The influenza virus changes in every season requiring a new vaccine. The older vaccine is less effective.
· Identification and isolation of the antigen.
· Production of the vaccine either in animals or in the laboratory.
· Testing the vaccine in test tubes and animals.
· Manufacture of the vaccine according to Good manufacturing standards.
STAGES OF VACCINE DEVELOPMENT: Clinical phase testing in humans
STAGES OF VACCINE DEVELOPMENT: Clinical phase testing in humans, con’t.· Phase 1 clinical trials: small trials in healthy volunteers of the same age and gender as the targeted patients to test safety and evoking immunity. Vaccines for children are first tested in adults. In a few cases the experimental group may be challenged with an extenuated or modified version of the pathogen
· Phase 2 clinical trials: in a large group of individuals at risk of getting the disease. patients with the infection to test efficacy (immune response), proposed dose, schedule of immunization, method of delivery, safety, adverse effects. The trial is blinded, randomized and includes a placebo.
· Phase 3 clinical trials: test the vaccine in a large number of people in tens of thousands with the aim of testing is to assess safety and efficacy (prent disease, prevent infection, producing antibodies).
THE SALK POLIO VACCINE TRIALS[1]· Approval and licensing the use of the vaccine for use followed by manufacturing under quality control.
· Phase 4: Post marketing trials involve long term monitoring of efficacy and safety.
SOME OF THE CHILDREN WHO PARTICIPATED IN THE SALK VACCINE TRIAL· Dr. Salk was made by cultivating 3 strains of the polio vaccine in monkeys. The virus was then separated and was killed using formaldehyde. The Salk vaccine was called the Inactivated Polio Vaccine (IPV)given by injection.
· On 23 January 1953, Jonas Salk of Pittsburgh presented the results of his tests of a “killed virus” polio vaccine on 161 children. The level of antibodies in the blood rose and the children had no adverse effects.
· In 1954, Across the United States, 623 972 schoolchildren were injected with vaccine or placebo, and more than a million others participated as “observed” controls.
· The results, announced in 1955, showed good statistical evidence that Jonas Salk’s killed virus preparation was 80-90% effective in preventing paralytic poliomyelitis.
INFLUENZA VACCINE[2]Figure: “Polio pioneers”—some of the many children who took part in trials of poliomyelitis vaccine.
MEASLES VACCINE[3]· Comparison of the IIV4 against the IIV3 in the Northern hemisphere influenza season of 2014-2015.
· Younger (18-60) and older (>60yr) adults were randomized 2:2:2:1:1 to receive various 3 lots of IIV4 or 2 lots IIV3 influenza vaccines.
· 21 days after vaccination hemagglutination antibodies were measured. Seroprotection rates were >98% in the younger and >90% in the older adults. There were no differences between the two vaccines and the various lots.
· IIV4 and IIV3 had similar safety profiles.
HUMAN PAPILLOMA VIRUS VACCINE[4]· A non-inferiority multi-centre parallel randomized double-blind trial to compare the EZ vs AIK-C strains of measles vaccines.
· 200 infants aged 8-12 months were randomized to EZ and AIK-C measles vaccines. Blood samples were taken before and 60 days after the vaccination. The outcome was anti-measles antibodies
· Seroconversion was 76.1% for EZ and 58.7% for AIK-C.
REFERENCES:· HPV vaccine is made against 9 strains of the virus (6, 11, 16,18, 31, 33, 45, 52, and 58).
· Efficacy and Immunogenicity were studied in 14,215 women aged 16-26 years in a phase 2/3 randomized, international, double blind study.
· Intramuscular injections were given at day 1, month 2, and month 6. Serum was collected for analysis of antibodies. Swabs of the labia, vulva, perineum, and cervix were obtained for HPV DNA testing and for cytology (PAP smear).
· Results showed that the vaccine prevented disease and generated antibody response.
1. BMJ. 1998 Oct 31; 317(7167): 1233–1236.
2. Hum Vaccin Immunother. 2018 Mar 4;14(3): 596-608.
3. Vaccine. 2018 Jan 29;36(5):631-636.
4. N Engl J Med. 2015 Feb 19;372(8):711-23.