Question

Describe the principles of vaccination and/or immunization. When would it be more effective to inject a modified toxin, as opposed to a cell or virus, as the content of the vaccination?

Answer 1

Immunity is the ability to tolerate self- antigens and mount and immune response to a foreign antigen. Vaccination and immunization create active and passive immunity in a human.

Vaccination is the process which administering the vaccine and immunization is the processes that occur in the body after the vaccination is administered. Hence, immunization involves both vaccination and immunity following vaccination.

Passive immunity is injection of antibodies against the pathogen from one organism to another organism. These injected antibodies will be able to neutralize the antigen on the pathogen and prevent infection. Passive immunity is temporary immunity. Antibodies are transferred across placental barrier that protect the fetus/child against infections till its own system is developed. Homologous pooled human antibody (immune globin), homologous human hyperimmune globulin, and heterologous hyperimmune serum are three types of passive immunization in humans. In homologous pooled human antibody immunization, serum IgG from many humans is pooled and injected into donor that require them. As it is from different donors, it may have different antibodies apart from specific antibody. It is used for postexposure prophylaxis for hepatitis A and measles. Hyperimmune globin is also similar, except the specific antibody is purified from the serum of donor and then used for vaccination. It is used for postexposure prophylaxis of hepatitis B, rabies, tetanus, and varicella.

Immune globulins are polyclonal. However, nowadays monoclonal antibodies can also be synthesized by hybridoma technology. Single B cells are immortalized to produced more antibodies that recognize a single epitope of the antigen. Such antibodies are used for treatment of breast cancer, B-cell chronic lymphocytic leukemia, non-Hodgkin lymphoma, respiratory syncytial virus (RSV) infection (palivizumab) etc.

The immune system is able to distinguish between self and non-self-antigens. Non-self-antigens are antigens present on bacteria, viruses and other pathogens, while molecules present on host cell surface are self-antigens. Non self-antigens can be either live or attenuated. Immunity is development of a B or T cell response to the non-self-antigens when encountered by the host immune system. The antigens even when present on a dead pathogen can illicit an immune response. This is basis for active immunity following vaccination with a live attenuated, inactivated or dead bacteria or virus. Protein antigens develop a stronger immune response than carbohydrate antigens. Active immunity is lifelong as memory cells are produced which can generate an antibody response when re-stimulated by the antigen. Normally. A person gains active immunity when infected by the pathogen that is lifelong (except malaria). Active vaccination and immunization can stimulate either humoral (antibody) or cell mediated (T lymphocytes) immunity. Vaccination leads to entry of the antigen into the human system where it will stimulate the immune system to mount an immune response similar to the infection. However, as these pathogens are either inactivated, attenuated or dead, they do not cause infection in host. Factors affecting vaccination include maternal antibody/adjuvant presence, nature/ dose of antigen, route of administration, age, nutrition, genetics, and other infections.

Vaccines are of two types: Live attenuated or inactivated. In live attenuated vaccines, the wild type pathogen is alive but has lost its ability to cause infection. It can replicate and induce an immune response but cannot cause disease. Inactivated vaccines contain whole viruses or bacteria or fraction of them. They are usually cultured and their disease- causing ability is inactivated or attenuated. They have to be administered in multiple doses as compared to live attenuated vaccines that require small doses. Polysaccharide vaccines that have long chain polysaccharides have been developed for Salmonella typhi that can illicit immune response.

Vaccination and immunization should only affect the humans and should not affect other animals. There should be no carrier state or sub-clinical infection developed by the vaccine. High level of herd immunity is required for the vaccine to be effective and spread from person to person of the infectious agent is prevented. Example is small pox vaccine. Ultimate aim of vaccination is to eradicate the bacteria or virus. Aim of immunization is development of immunity in the person being vaccinated, so that the person is immune to subsequent infection by the pathogen.

A modified toxin is injected when the toxin is the major virulence factor on the pathogen is causing the disease. The cell surface antigens do not have any role in targeting the immune response. The toxin will be able to initiate an immune response. However, booster doses are required. As only toxins are injected, there is no disease induced as no bacteria or virus has been injected, thereby not infecting and dividing in host cells. However, if the antigenic determinant that induces the immune response is the cell or virus is expressed on the cell surface or is an important component of organelles, then whole cells/virus is used for vaccination. Integrity of the cell component are needed for immune response. Replication of the bacteria/virus in host cell may be required for stimulating immune system.