The purpose of viral vaccines is to use the adaptive immune response of the host to prevent viral disease. Several vaccines have proved to be remarkably effective at reducing the incidence of viral disease (Figure 1). Vaccination is the most cost-effective method of prevention of serious viral infections.

Fig1. Annual incidence of various viral diseases in the United States. Date of introduction of vaccine indicated by arrow. (Data from the Centers for Disease Control and Prevention.)

A. General Principles

Immunity to viral infection is based on the development of an immune response to specific antigens located on the sur face of virus particles or virus-infected cells. For enveloped viruses, the important antigens are the surface glycoproteins. Although infected animals may develop antibodies against virion core proteins or nonstructural proteins involved in viral replication, that immune response is believed to play little or no role in the development of resistance to infection.

Vaccines are available for the prevention of several significant human diseases. Currently available vaccines (Table 1) are described in detail in the chapters dealing with specific virus families and diseases.

Table1. Virus Vaccines Approved in the United States

The pathogenesis of a particular viral infection influences the objectives of immunoprophylaxis. Mucosal immunity (local IgA) is important in resistance to infection by viruses that replicate in mucosal membranes (rhinoviruses, influenza viruses, rotaviruses) or invade through the mucosa (papillomavirus). Viruses that have a viremic mode of spread (polio, hepatitis A and B, yellow fever, varicella, mumps, measles) are controlled by serum IgG antibodies. Cell-mediated immunity also is involved in protection against systemic infections (measles, herpes).

Certain characteristics of a virus or of a viral disease may complicate the generation of an effective vaccine. The existence of many serotypes, as with rhinoviruses, and of large numbers of antigenic variants in animal reservoirs, as with influenza virus, makes vaccine production difficult. Other hurdles include the integration of viral DNA into host chromosomal DNA (retroviruses) and infection of cells of the host’s immune system (HIV).

B. Killed-Virus Vaccines

Inactivated (killed-virus) vaccines are made by purifying viral preparations to a certain extent and then inactivating viral infectivity in a way that does minimal damage to the viral structural proteins; mild formalin treatment is frequently used (Table 2). For some diseases, killed-virus vaccines are currently the only ones available.

Table 2. Comparison of Characteristics of Killed- and Live-Virus Vaccines

Killed-virus vaccines prepared from whole virions generally stimulate the development of circulating antibody against the coat proteins of the virus, conferring some degree of resistance to that virus strain.

Advantages of inactivated vaccines are that there is no reversion to virulence by the vaccine virus and that vaccines can be made when no acceptable attenuated virus is available. Disadvantages of killed-virus vaccines include relatively brief immunity requiring boosting shots to maintain effectiveness, poor cell-mediated response, and occasional hypersensitivity to subsequent infection.

C. Attenuated Live-Virus Vaccines

Live-virus vaccines use virus mutants that antigenically overlap with wild-type virus but are restricted in some step in the pathogenesis of disease (see Table 2).

The genetic basis for the attenuation of most viral vaccines is not known because they were selected empirically by serial passages in animals or cell cultures (usually from a species different from the natural host). As more is learned about viral genes involved in disease pathogenesis, attenuated candidate vaccine viruses can be engineered in the laboratory.

Attenuated live-virus vaccines have the advantage of acting more like the natural infection with regard to their effect on immunity. They multiply in the host and tend to stimulate longer-lasting antibody production, induce a good cell-mediated response, and induce antibody production and resistance at the portal of entry (Figure 2). Disadvantages of attenuated live-virus vaccines include a risk of reversion to greater virulence, severe infection in immunocompromised hosts, and limited storage and shelf life in some cases. Additionally, unrecognized adventitious agents have been found in vaccine stocks (eg, simian polyomavirus SV40, porcine circovirus) .

Fig2. Serum and secretory antibody response to orally administered, live attenuated polio vaccine and to intramuscular inoculation of killed polio vaccine. (Reproduced with permission from Ogra PL, Fishaut M, Gallagher MR: Viral vaccination via the mucosal routes. Rev Infect Dis 1980;2:352. By permission of Oxford University Press.)

D. Proper Use of Vaccines

 An effective vaccine does not protect against disease until it is administered in the proper dosage to susceptible individuals.

Failure to reach all sectors of the population with complete courses of immunization is reflected in the continued occurrence of measles outbreaks in populations who refuse immunization. Herd immunity refers to the fact that the risk of infection among susceptible individuals in a population is reduced by the presence of adequate numbers of immune individuals. This effect is reflected in dramatic decreases in the incidence of disease, even when all susceptible individuals have not been vaccinated. However, the threshold of immunity needed for this indirect protective effect depends on many factors, including the transmissibility of the infectious agent, the nature of the vaccine-induced immunity, and the distribution of the immune individuals. Individuals protected by herd immunity remain susceptible to infection upon exposure. This can lead to outbreaks of disease when a group of susceptible individuals accumulate, such as mumps outbreaks among university students in the United States.

Certain viral vaccines are recommended for use by the general public. Other vaccines are recommended only for use by persons at special risk because of occupation, travel, or lifestyle. In general, live-virus vaccines are contraindicated for pregnant women and immunocompromised individuals.

 E. Future Vaccine Prospects

Molecular biology and modern technologies are combining to allow novel approaches to vaccine development. Many of these approaches avoid the incorporation of viral nucleic acid in the final product, improving vaccine safety. Examples of what is ongoing in this field can be listed as follows. The ultimate success of these new approaches remains to be determined.

1. Use of recombinant DNA techniques to insert the gene coding for the protein of interest into the genome of an avirulent virus that can be administered as the vaccine (eg, vaccinia virus).

2. Including in the vaccine only those subviral components needed to stimulate protective antibody, thus minimizing the occurrence of adverse reactions to the vaccine.

3. Use of purified proteins isolated from purified virus or synthesized from cloned genes (a recombinant hepatitis B virus vaccine contains viral proteins synthesized in yeast cells). Expression of cloned gene(s) sometimes results in formation of empty virus-like particles.

 4. Use of synthetic peptides that correspond to antigenic determinants on a viral protein, thus avoiding any possibility of reversion to virulence since no viral nucleic acid would be present, although the immune response induced by synthetic peptides is considerably weaker than that induced by intact protein.

5. Development of edible vaccines whereby transgenic plants synthesizing antigens from pathogenic viruses may provide new cost-effective ways of delivering vaccines.

 6. Use of naked DNA vaccines—potentially simple, cheap, and safe—in which recombinant plasmids carrying the gene for the protein of interest are injected into hosts and the DNA produces the immunizing protein.

7. Administration of vaccine locally to stimulate antibody at the portal of entry (eg, aerosol vaccines for respiratory disease viruses).

مواضيع ذات صلة

Development of Vaccines for Tuberculosis and Meningitis

Development of Vaccines for Viral Hepatitis, Coronavirus, and Norovirus

Development of Powerful Influenza Vaccines

Vaccines for HIV and Ebola Virus

Vaccines for Diseases Associated with Urban Areas in the Developing Countries

HIV Vaccine

Yellow Fever Vaccine

Tuberculosis Vaccine

Rotavirus Vaccines

Pertussis Vaccines

Haemophilus Influenza Vaccines

Hepatitis A Vaccines