Vaccination Against the Covid-19 Disease – Part 2

Author’s note:  This blog is part of a series on the current status of the Covid-19 vaccination program in the United States.  All information contained herein was obtained from peer reviewed scientific journals and publications as well as legitimate vetted science-based websites.  These sources are referenced such that you may obtain further information from them.  All information is based on scientific facts known at the time of publication.

A brief history of vaccination

Part 1 of this series detailed some of the epidemics and pandemics that have afflicted humans here on Earth.  

Part 2 will describe the history of efforts made by physicians, scientists, and researchers to develop vaccines against the causative agents of some of these diseases.

Edward Jenner performed some of the first documented vaccinations against smallpox in 1796 by obtaining fluid from cow pox lesions and scratching it into the surface of a patient’s skin to prevent smallpox.  He named the material a “vaccine” (1). However, this methodology was not new.  Records from the 1500’s document the use of this procedure in China and India using material from the smallpox lesion itself (2).

Almost one hundred years later in the 1880’s, Louis Pasteur and his colleagues in Europe discovered “microbes” as the cause of many diseases.  Pasteur’s work resulted in preparation of vaccines for several diseases including rabies (3).  He and his colleagues used methods to “attenuate” (i.e., weaken) the microbes, and then use this preparation as a vaccine.  Methods of attenuation included exposure of the microbe preparation to oxygen and heat (4).  Additionally, serial cultivation of a pathogen in vitro outside of the host proved to weaken that microbe’s virulence (5).  

In the 1930’s and 1940’s, pertussis vaccine was prepared using inactivation by exposing the whole cell preparation to formalin (6,7).  This method was subsequently shown to be successful in controlling serious disease.  During this same time researchers developed rabies and oral polio vaccines by culturing and passing the microbes in chicken embryos and mice.  This provided another method of attenuation by culturing microbes in abnormal hosts (8,9).  While effective, these methods were not optimal as mice especially were not sterile hosts.

This issue was resolved when researchers found that they could culture cells in vitro and use them as a substrate for growing viruses (10).   By growing disease causing viruses in culture using many passages, researchers were able to select clones that could be used to prepare vaccines.  The oral polio vaccine of Albert Sabin and the mumps, measles, varicella, and rubella vaccines were all made using this methodology (11).

In addition to tetanus and diphtheria toxoids, which are also produced using inactivation, several vaccines are composed of partly or fully purified proteins. The influenza vaccines used today are manufactured by growing the viruses in embryonated eggs and then breaking up the whole virus with detergents. The viral hemagglutinin protein is purified to serve as the vaccine antigen.  However, other components of the influenza virus may be present in the final product as well (12).

The development of the technique of genetic engineering toward the end of the 20th century has greatly impacted vaccine development. The first successful effort resulted in the vaccine against hepatitis B. Initially, the hepatitis B surface antigen particles from the serum of naturally infected patients were purified and any residual live virus was inactivated (13). However, this procedure was not optimal.

Later the coding sequence for the S antigen was placed into yeast cells and large quantities of surface-antigen particles were able to be produced in vitro (14).  Genetic engineering has been used to produce many candidate antigens for vaccines in yeast, animal cells, or insect cells producing an antigen in culture.  

We will see in the next part of the series exactly how the manufacturing of the current vaccines against the SARS-CoV-2 virus have built upon this original work resulting in safe and highly effective protection against Covid-19 disease.


  1. Kenneth C. Davis.  More Deadly Than War: The Hidden History of the Spanish Flu and the First World War.  2018.  Henry Hold and Company, New York.  ISBN 978-1-250-14512-3.
  1. The Historical Medical Library of The College of Physicians of Philadelphia.  The History of Inoculation and Vaccination for the Prevention and Treatment of Disease.  Lecture Memoranda. A.M.A. Meeting, Minneapolis.  Burroughs Wellcome and Co.  London, 1913.
  1. Pasteur L. De l’attenuation du virus du choléra des poules. C R Acad Sci Paris. 1880;91:673–680.
  1. Pasteur L. Mèthode pour prévenir la rage apres morsure. C R Acad Sci Paris. 1885;101:765–772.
  1. Madsen C. Vaccination against whooping cough. JAMA. 1933;101:187–188. 
  1. Sauer LW. Whooping cough: Prevention and treatment. Med Clin North Am. 1946;30:45–59. 
  2. Koprowski H, Jervis GA, Norton TW. Immune responses in human volunteers upon oral administration of a rodent-adapted strain of poliomyelitis virus. Am J Hyg. 1952;55(1):108–124.
  1. Fox JP, Koprowski H, Conwell DP, Black J, Gelfand HM. Study of antirabies immunization of man: Observations with HEP Flury and other vaccines, with and without hyperimmune serum, in primary and recall immunizations. Bull World Health Organ. 1957;17(6):869–904.
  1. Enders JF, Weller TH, Robbins FC. Cultivation of the Lansing strain of poliomyelitis virus in cultures of various human embryonic tissues. Science. 1949;109(2822):85–87.
  1. Sabin AB, Hennessen WA, Winsser J. Studies on variants of poliomyelitis virus. I. Experimental segregation and properties of avirulent variants of three immunologic types. J Exp Med. 1954;99(6):551–576.
  1. Cate TR, Couch RB, Kasel JA, Six HR. Clinical trials of monovalent influenza A/New Jersey/76 virus vaccines in adults: Reactogenicity, antibody response, and antibody persistence. J Infect Dis. 1977;136(Suppl):S450–S455.
  1. Hilleman MR, McAleer WJ, Buynak EB, McLean AA. The preparation and safety of hepatitis B vaccine. J Infect. 1983;7(Suppl 1):3–8. 
  1. Valenzuela P, Medina A, Rutter WJ, Ammerer G, Hall BD. Synthesis, and assembly of hepatitis B virus surface antigen particles in yeast. Nature. 1982;298(5872):347–350.

Questions and comments may be sent to the author directly.
Clifford M Chapman
Senior Consultant
Medi-Sci Consultants