Saturday, July 04, 2020

The history of vaccine development,

The history of vaccine development, divided into live and attenuated vaccines, although the distinction between the two is beginning to blur with the development of vectored vaccines. 

(A live vector vaccine is a vaccine that uses a chemically weakened virus to transport pieces of the pathogen in order to stimulate an immune response.[6] Viruses expressing pathogen proteins are currently being developed as vaccines against these pathogens, based on the same rationale as DNA vaccines. The genes used in such vaccines are usually antigen coding surface proteins from the pathogenic organism. They are then inserted into the genome of a non-pathogenic organism, where they are expressed on the organism's surface and can elicit an immune response.

An example is the hepatitis B vaccine, where Hepatitis B infection is controlled through the use of a recombinant vaccine, which contains a form of the hepatitis B virus surface antigen that is produced in yeast cells. The development of the recombinant subunit vaccine was an important and necessary development because hepatitis B virus, unlike other common viruses such as polio virus, cannot be grown in vitro.

T-lymphocytes recognize cells infected with intracellular parasites based on the foreign proteins produced within the cell. T cell immunity is crucial for protection against viral infections and such diseases as malaria. A viral vaccine induces expression of pathogen proteins within host cells similarly to the Sabin Polio vaccine and other attenuated vaccines. However, since viral vaccines contain only a small fraction of pathogen genes, they are much safer and sporadic infection by the pathogen is impossible. Adenoviruses are being actively developed as vaccines.)


Active immunization began in China and in India with the practice of variolation, in which the smallpox virus itself, given artificially, prevented people from developing scarring from natural smallpox, although inevitably some variolated individuals died from the inoculation itself . The dawn of vaccinology came with the observations of Edward Jenner as to the efficacy of cowpox (or some virus related to cowpox, the identity of which is still uncertain) in preventing subsequent smallpox. This was the beginning of live, attenuated vaccines. More than 80 years later, Louis Pasteur found means of attenuating organisms in the laboratory . Apparently, the first organism attenuated simply by ageing on the laboratory bench, was the agent of fowl cholera, now called Pasteurella multocida. Pasteur and his colleagues then studied heat, desiccation, exposure to oxygen, and passage in atypical host species as means to attenuate anthrax bacilli and rabies virus.


The next signal advance in vaccine development occurred later in the nineteenth century in the USA and in Pasteur's Institute, and that was the chemical inactivation of whole bacteria. Daniel Salmon and Theobald Smith described the principle by inactivating a Salmonella (later named after Salmon) that caused disease in pigs. This work and that of the French group led eventually to vaccines against typhoid, plague, and cholera, and subsequently pertussis, all based on inactivated whole bacilli . Progress continued in the first half of the twentieth century, based first on the Pastorian method. Two powerful vaccines developed at that time were Bacille Calmette Guérin for tuberculosis, which was a Mycobacterium bovis passaged in artificial culture medium by Albert Calmette and Camille Guérin; and yellow fever, which was a virus adapted to growth first in mouse brain and then in the chorioallantois of chicken eggs by Max Theiler  Later in the century Herald Cox used the embryonated egg to develop a vaccine against the rickettsial disease, typhus. In addition, the discoveries of Emil Behring, Emile Roux, and Shibasuro Kitasato relative to toxin production by the diphtheria and tetanus bacilli permitted Gaston Ramon to inactivate the toxins with formalin to produce what are now called toxoids. The toxoid vaccines rapidly controlled diphtheria and tetanus ( Just after World War II the technology of cells grown in vitro for virus cultiva-toxoids. The toxoid vaccines rapidly controlled diphtheria and tetanus . Just after World War II the technology of cells grown in vitro for virus cultivation was demonstrated by Enders, Weller, and Robbins and then built upon by many other researchers. Virus culture permitted the development of numerous vaccines, including inactivated polio, live polio, measles, mumps, rubella, adenovirus, varicella, and later on rotavirus and zoster. It also permitted a switch from crude rabies vaccines grown in animal brain or embryonated eggs to a more refined and potent cell culture vaccine (. Japanese encephalitis and tick-borne encephalitis vaccines were also first developed in animal tissue and then switched more recently to cell culture. Hepatitis A is an example of a whole inactivated virus vaccine, similar to the inactivated polio vaccine .

On the bacterial side advances were made through two means: identification of capsular polysaccharides or other components that could immunize without the remainder of the bacilli, and the discovery that conjugation with protein could greatly increase the immunogenicity of polysaccharides . Thus, powerful vaccines have been developed against the three major causes of meningitis in children and invasive infections in adults: Haemophilus influenzae type b, meningococci and pneumococci. For each of the three pathogens vaccines were developed both as polysaccharides and as protein-conjugated polysaccharides. For H. influenzae type b the conjugate vaccine has completely replaced the polysaccharide because infants do not respond to the latter; for meningococcal infections both types of vaccines are in use; and for pneumococcus the polysaccharide vaccine is given to the elderly whereas the conjugate vaccine is given to infants. However, in the pneumococcal case the serotypes contained in the two vaccines are different. A capsular polysaccharide from the typhoid bacillus is used to vaccinate against that disease (Chap. 9). In the way of vaccines made from purified proteins, aside from the diphtheria and tetanus toxoids, there are three made from naturally produced substances: the original hepatitis B surface antigen vaccine made from the plasma of infected donors (Chap. 25), the anthrax vaccine made from secreted protective antigen, and acellular pertussis vaccines containing 1—5 components of the organism (Chap. 10). In addition, most influenza vaccines depend on the viral hemagglutinogen protein,


No comments: