1. History of vaccines - main vaccine types (1).pdf
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1. A short history of vaccines and main vaccine types Vaccination Definition (Prophylactic) vaccination is a deliberate attempt to protect humans (and other animals) against a future infection/disease. Aims of vaccination • Protection of an individual • Protection of a group (‘herd’) • Elimi...
1. A short history of vaccines and main vaccine types Vaccination Definition (Prophylactic) vaccination is a deliberate attempt to protect humans (and other animals) against a future infection/disease. Aims of vaccination • Protection of an individual • Protection of a group (‘herd’) • Elimination of a disease • Eradication of a disease To date > 30 diseases are vaccine preventable Impact of vaccination The impact of vaccination on global health cannot be overestimated Vaccination is one of the greatest medical achievements, together with e.g. safe water and sanitation and antibiotics Vaccination prevents an estimated 3 million deaths every year and saves 750 000 children from disability (WHO) (in non-pandemic circumstances). Impact of vaccination in the US Disease and death, before and after introduction of vaccines Before vaccination After vaccination Disease Cases/year Deaths/year Cases/year Deaths/year Tetanus 580 472 41 4 Diphteria 21053 1822 0 0 Pertussis 200752 4034 15632 27 Paralytic polio 16316 1879 0 0 Measles 530217 440 55 0 Mumps 162344 39 6584 0 152 NA 11 0 Congenital rubella Roush et al. JAMA. 2007;298(18):2155-2163 Impact of vaccination Estimated deaths averted with vaccines in low-income countries Smallpox: a vaccine success story For many centuries smallpox was a major disease burden worldwide 1967 global eradication campaign was launched with 80% coverage 1977 last natural case in Somalia Courtesy of CDC/James Hicks 1980 WHO declared smallpox eradicated In Belgium smallpox vaccination was officially stopped in 1981 WHO, World Health Organization About 30 vaccines are currently preventable by vaccination and many vaccines are in the pipeline • Smallpox • Cytomegalovirus (CMV) /zoster • M-pox • Anthrax • RSV https://www.who.int/teams/immunization-vaccines-and-biologicals/diseases Infectious diseases are an important cause of childhood (<5) mortality Every year 8-9 million children die before the age of 5 68% of deaths are caused by infectious diseases Liu et al. Lancet 2016; https://doi.org/10.1016/S0140-6736(16)31593-8 A walk through vaccine history… Objective: • To know about the most important milestones in vaccine history and the approximate period in which these novel technologies/vaccines became available • Exact years and names of all the pioneers do not need to be memorized. Obviously you know Jenner, Pasteur, Koch, … Want to know more? Check e.g. www.historyofvaccines.org Modern vaccine concepts stem from early empirical approaches Inoculation Practised in various Asian and African countries for centuries, widely used by the Ottomans for a long period of time Variolation (engrafting- ‘inenten’) 1720: Introduced in Europe by Lady Mary Montagu. Mortality associated with variolation was 10 times lower than that associated with naturally occurring smallpox Lady Montagu (18th Century) Bonanni et al. Chapter 1 in: Garçon et al. Understanding Modern Vaccines, Perspectives in vaccinology, Vol 1, Amsterdam. Elsevier 2011;p1–24 The principle of vaccination was discovered before the knowledge of pathogens and the immune system 1774: Benjamin Jesty, a cattle breeder inoculated his wife and 2 children with cowpox. He had observed that dairy maids seemed to be protected from smallpox if they had been infected by cowpox. 1796: smallpox vaccine introduced by Edward Jenner Jenner called this practice ‘vaccination’ from the Latin word for cow, ‘vacca’ • liquid from the pustules of cowpox was used to inoculate humans to prevent smallpox Empirical approach • no knowledge of microorganisms or the immune system at the time The ‘Jenner approach’ to vaccination is considered as a primitive example of a live-attenuated vaccine Dr. Edward Jenner Jenner’s contributions • Passing cowpox from one person to another, thus allowing large scale vaccination without depending on sporadic outbreaks of disease in cattle. • Published as ‘Variolae Vaccinae’ in 1798 Bonanni et al. Chapter 1 in: Garçon et al. Understanding Modern Vaccines, Perspectives in vaccinology, Vol 1, Amsterdam. Elsevier 2011;p1–24 The ‘germ theory’ opened the door to a pathogen-based approach Louis Pasteur Robert Koch From ‘bad air’ and ‘body imbalance’ to Microorganisms microorganisms as causes of infectious diseases Courtesy of CDC/Dr Ray Butler Courtesy of CDC/Janice Haney Carr/Jeff Hageman M.H.S. Bonanni et al. Chapter 1 in: Garçon et al. Understanding Modern Vaccines, Perspectives in vaccinology, Vol 1, Amsterdam. Elsevier 2011;p1–24 Pathogen isolation and vaccine availability do not directly correlate RSV SARS-CoV-2 virus RSV vaccine SARS-CoV-2vaccine Papillomavirus HPV vaccine Rotavirus Rotavirus vaccine Zoster vaccine Varicella zoster virus Varicella vaccine Hepatitis A virus Hepatitis A vaccine Haemophilus influenza B HiB vaccine Hepatitis B virus Hepatitis B vaccine Neisseria meningitidis Meningitis vaccine Rubella virus Rubella vaccine Mumps virus Mumps vaccine Measles virus Measles vaccine Poliovirus Polio vaccine Streptococcus pneumonia Pneumococcus vaccine Influenza virus Influenza vaccine Flavivirus Yellow fever vaccine Corynebacterium diphtheria Diphtheria vaccine Mycobacterium tuberculosis Tuberculosis vaccine Clostridium tetani Tetanus vaccine Bordetella pertussis Pertussis vaccine Yersinia pestis Plague vaccine Vibrio cholerae Cholera vaccine Salmonella typhi Typhoid vaccine Rabies vaccine Rabies virus* Smallpox vaccine Smallpox* 1780 1880 1900 1920 1940 1960 1980 2000 2020 *During the development of the rabies and smallpox vaccines, it was discovered that the infectious agent was not a bacterium, although viruses would not be directly observed until the 1930s Bonanni et al. Chapter 1 in: Garçon et al. Understanding Modern Vaccines, Perspectives in vaccinology, Vol 1, Amsterdam. Elsevier 2011;p1–24 End of 19th century Major discoveries that supported progress in vaccine development Attenuation and inactivation of pathogens The discovery of pathogen attenuation in Pasteur’s lab is reported as due to an involuntary neglicence of one of his co-workers Attenuation of microorganisms through passages and production of ‘stocks’ of vaccines Louis Pasteur Rabies vaccine: chemically attenuated using formaldehyde (1885) Following years: vaccines against Salmonella typhi, Vibrio cholerae, Yersinia pestis (plague) Bonanni et al. Chapter 1 in: Garçon et al. Understanding Modern Vaccines, Perspectives in vaccinology, Vol 1, Amsterdam. Elsevier 2011;p1–24 To summarize: achievements in 18th and 19th centuries Vaccines against • Viral diseases smallpox – vaccinia rabies • Bacterial diseases typhoid fever (Salmonella typhi) cholera (Vibrio cholerae) plague (Yersinia pestis) End 19th- beginning 20th Century – before WWII Development of antitoxins and toxoids 1888 Roux and Yersin discovered diphteria toxin 1891 Behring and Kitasato developed antitoxin in sera of animals infected with diphteria 1891 First child treated with antitoxin (passive immunization) 1897 Paul Ehrlich – antigen/antibody (side chain theory) 1923 Alexander Glenny developed diphteria toxoid (formalin-treatment) 1926 Gaston Ramon developed diphteria and tetanus toxoids 1920s Major discoveries that supported progress in vaccine development Toxoids • Toxin from pathogen could cause disease • Toxoids concept (inactivated toxin) • The antitoxin concept (immune serum) Use of formaldehyde inactivation in vaccines originated by accident First Nobel Prize in Medicine in 1901 to von Behring for the discovery of antibodies and passive immunotherapy of diphtheria Bonanni et al. Chapter 1 in: Garçon et al. Understanding Modern Vaccines, Perspectives in vaccinology, Vol 1, Amsterdam. Elsevier 2011;p1–24 Major discoveries that supported progress in vaccine development Discovery of adjuvants by Gaston Ramon Use of aluminium salts as vaccine adjuvants by Alexander Glenny Bonanni et al. Chapter 1 in: Garçon et al. Understanding Modern Vaccines, Perspectives in vaccinology, Vol 1, Amsterdam. Elsevier 2011;p1–24 1920s 1925: chance and necessity … While producing diphtheria antitoxin in horses by injecting diphtheria toxoid, Ramon noted that horses with spontaneous abscesses at the injection site produced greater serum antitoxin titres He attributed this to ‘banal germs of the skin’ Subsequently he experimented with substances (such as tapioca) able to induce sterile abscesses and observed an enhanced antitoxin response Gaston Ramon He called these substances adjuvants from the Latin adjuvare, to help Ramon. Annales Institut Pasteur 1926;40:1–10; Bonanni et al. Chapter 1 in: Garçon et al. Understanding Modern Vaccines, Perspectives in vaccinology, Vol 1, Amsterdam. Elsevier 2011;p1–24 1920s 1926: aluminium salts – the beginning of an era … Alexander Glenny established that adding aluminium enhances antibody responses against diphtheria toxoid in guinea pigs1 Aluminium salts enhance antibody response to diphtheria toxoid in humans2 (1932) Alexander Glenny 2. 1. Glenny et al. J Path Bact 1926;29:38–45; 2. Park and Schroder. Am J Public Health Nations Health 1932;22:7–16 1920s Tuberculosis Calmette and Guérin developed a vaccine for tuberculosis by culturing a bovine strain in bovine bile for 230 passages over 13 years. This is the BCG strain Trials were performed in 1921 Vaccine available in 1927 BCG is one of the most widely used of all current vaccines: > 80% of neonates and infants in countries where it is part of the national childhood immunization programme. 1920-1930s Influenza 1933 - discovery of Influenza A 1936 - development of influenza A vaccine 1968 – licensing of influenza vaccines in the US End 1970’s– large scale influenza vaccination campaigns every autumn Pertussis 1900 - Bordetella pertussis discovered by Jules Bordet 1929 - Pertussis whole cell (Pw) vaccine in 1929 1940s (end of) – Whole cell pertussis (Pw) widely used in US 1948 - Combination vaccine, diphteria-tetanus-Pw is available 1930s–1950s Major discoveries that supported progress in vaccine development Growing viruses Embryonated eggs (1930s) Using the egg system, Max Theiler at Rockefeller developed an effective yellow fever vaccine in the 1930s and received the Nobel Prize in Medicine in 1951 Cell culture (1950s) Enders, Weller & Robbins at Harvard received the Nobel Prize in Medicine in 1954 for demonstrating the ability of polio viruses to grow in cell cultures Bonanni et al. Chapter 1 in: Garçon et al. Understanding Modern Vaccines, Perspectives in vaccinology, Vol 1, Amsterdam. Elsevier 2011;p1–24 1950-1960s Jonas Salk IPV The polio experience Poliovirus propagation into human cell culture by Jonas Salk enabled the development of IPV, which was introduced in humans in 1950 In parallel with IPV development, Albert Sabin was working on the live-attenuated OPV, which replaced IPV in many countries in the 1960s Albert Sabin OPV IPV, inactivated polio vaccine; OPV, oral polio vaccine Bonanni et al. Chapter 1 in: Garçon et al. Understanding Modern Vaccines, Perspectives in vaccinology, Vol 1, Amsterdam. Elsevier 2011;p1–24 1970s Combination vaccines 1970s: A combined MMR vaccine was developed to minimise the total number of injections in infants • Clinical trial data demonstrated that a combined antigen vaccine can be effective and can have an acceptable safety profile Measles MMR, measles-mumps-rubella Mumps Rubella Bonanni et al. Chapter 1 in: Garçon et al. Understanding Modern Vaccines, Perspectives in vaccinology, Vol 1, Amsterdam. Elsevier 2011;p1–24 1970s–1980s Major discoveries that supported progress in vaccine development Split/subunit antigens (1970s) Recombinant DNA protein antigens (1980s) Whole pathogen Split Subunit In 2008, zur Hausen received the Nobel Prize in Medicine for his discovery of human papillomaviruses causing cervical cancer and his work that would eventually lead to the development of a preventive vaccine Bonanni et al. Chapter 1 in: Garçon et al. Understanding Modern Vaccines, Perspectives in vaccinology, Vol 1, Amsterdam. Elsevier 2011;p1–24 1980s–1990s Major discoveries that supported progress in vaccine development Conjugation of polysaccharides (1980s) Reassortment of viral genes (1990s) Bovine rotavirus Human rotavirus Polysaccharide Protein Human Human/bovine reassortment Bonanni et al. Chapter 1 in: Garçon et al. Understanding Modern Vaccines, Perspectives in vaccinology, Vol 1, Amsterdam. Elsevier 2011;p1–24; Strugnell et al. Chapter 3 in: Garçon et al. Understanding Modern Vaccines, Perspectives in vaccinology, Vol 1, Amsterdam. Elsevier 2011;p61–88 2000-2020 The accelerated development of innovative vaccine platforms: adenoviral vector vaccines Coughlan et al. Mol Ther 2022; 30: 1822-49 2000-2020 The accelerated development of innovative vaccine platforms: mRNA vaccine technology Katalin Karikó Ugur Sahin and Ozlem Türeci Whatisbiotechnology.org Most vaccine technologies are still in use today… A short history of vaccinology: major milestones 1798 1885 WWI WWII 2 1 Smallpox Rabies Diphteria Pertussis Tetanus BCG Yellow Fever 3 2000 2020 4 5 Polio Adjuvants Vectored vaccines Mumps Delivery mRNA HBsAg Rubella Measles Varicella 1- microbiology 2 - cell culture – virology 3 - molecular biology 4 - adjuvants/delivery (VLP) platforms 5 - (adenoviral) vector – mRNA vaccines
