Live Attenuated and Inactivated Vaccines

Vaccines consist of either live attenuated or inactivated microorganisms. Live attenuated vaccines use a weakened form of the pathogen, which after administration replicates and induces an immune response. Inactivated vaccines are prepared from whole bacteria or virus, or a fractional antigenic protein of an organism. Vaccines may be protein-based, pure polysaccharide-based, or conjugate polysaccharide-based. Protein-based vaccines typically include subunits of microbial proteins, inactivated bacterial toxins, or recombinant DNA segments expressed in another living cell.

Pure polysaccharide-based vaccines are generally less immunogenic than protein-based vaccines; however, when conjugated to a protein or toxoid their immunogenicity is increased. Vaccines initiate immune responses mediated by macrophages and lymphocytes, i.e., they induce active immunity. Antibodies are produced against specific infective agents or their toxins. Protective antibodies, which may be produced in response to vaccines and their mechanisms of action, are listed in Box 1.

Box 1. Protective Antibodies and their Mechanisms of Action.
AntitoxinsInactivate toxic microbial protein products
OpsoninsFacilitate phagocytosis of microorganisms
LysinsDamage microbial cell membrane
AntiadhesinsPrevent adhesion of microorganisms to host cell components
Neutralizing antibodiesPrevent the proliferation of microorganisms

Neutralizing antibodies cannot readily diffuse into infected cells; they must interact with the target-organism before initial intracellular penetration. However, sensitized lymphocytes acting alone or antibodies interacting with lymphoid K-cells may recognize surface changes in infected cells and target them for destruction. Immunization with live attenuated organisms is more predictable than immunization with inactivated microorganisms in inducing long-term immunity.

Immunogenic responses to live attenuated and inactivated microorganisms develop more slowly than the incubation period of most pathogens. Therefore, vaccines must be administered prior to exposure to a specific etiologic agent. By contrast, “booster” re-immunization in a previously immune individual provides a rapid secondary (anamnestic) increase in immunity. The persistence of immunity may also be prompted by natural re-exposure to microorganisms and the presence of latent infections.