Dr. S.G. Deodhare, M.D., F.A.M.S
Former Professor of Pathology, Grant Medical College
and Dean, J.J. Group of
Hospitals, Mumbai.
deodhare_29@yaoo.com
Dr. S.G. Deodhare
OUTLINE
DNA Vaccines
Combination Vaccines
Conjugate Vaccines
Typhoid Conjugate Vaccine
References
Graphics
Table 1
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Vaccination is now recognized as having one of the most important and cost effective health promotion activities. The WHO estimates that current immunization programmes save more than 3.2 million lives annually and that full utilization of existing vaccines could save an additional 1.7 million lives per year.
Since the time of Edward Jenner, vaccination has been able to control eleven major diseases. These major diseases are: smallpox, diphtheria, tetanus, yellow fever, pertussis, poliomyelitis, measles, mumps, rubella, hepatitis B and Haemophilus influenzae type b.
The future of vaccines is particularly exciting with the developments in DNA vaccines, conjugate vaccines and the availability of combination vaccines.
DNA Vaccines
The development and widespread use of vaccines against infectious agents has been one of the triumphs of medical science. One reason for the success of these vaccines is that they excel at inducing antibodies, which are the principal agents of immune protection against most viruses and bacteria. There are, however, exceptions including medically important intracellular organisms like Mycobacterium tuberculosis, malarial parasite and possibly the human immunodeficiency virus (HIV) in which protection depends more on cell-mediated immunity than on induction of antibodies (humoral immunity).
The currently used vaccines, whether they are prepared from killed or inactivated whole cell, recombinant proteins or live attenuated organisms simulate antibody production. Moreover, the possibility of using live attenuated vaccines against viruses like HIV arouses concern about manufacturing procedures and the risks of using these vaccines to immunize large populations. For these reasons, a new approach to vaccination that involves the injection of a piece of DNA that contains the gene for the antigen of interest is under intensive investigation (Seder RA, Gurunathan Sanjay 1999).
A DNA vaccine contains a piece of circular DNA including a promoter, gene segment and terminal signal. This provides a platform for producing a specific antigen. These vaccines can either be used for direct vaccination or as tools to identify antigens that will elicit a protective immune response. Although the biological events following intramuscular infections of DNA vaccines are not fully understood, it is thought that the antigens encoded in the DNA is expressed in the cytoplasm of the muscle cell (via RNA and protein production), and presented to the endogenous MHC class I receptors, and also secreted from the cell (McDonnell WM, Askari FK 1996). In many respects, the outcome of this form of immunization mimics the action of live-attenuated or recombinant virus vaccine.
Because of their unique ability to elicit cellular responses, current targets for DNA vaccines include viruses (Herpes simplex virus, Human immunodeficiency virus, Hepatitis C virus, Human papilloma viruses), bacteria (Chlamydia, Tuberculosis) and parasites (Malaria, Leishmania).
Combination Vaccines
The present childhood vaccination schedule requires a minimum of 13 separate injections to immunize a child from birth to the age of six years. Combination vaccines merge into a single product antigen that prevents different diseases and/or protects against multiple strains of infectious agents causing the same disease. Thus, they increase coverage, decrease the number of injections in each clinic visit, and help to minimize the cost. Combination vaccines will play an important role in future childhood immunization strategies (American Academy of Pediatrics 1999).
There have been some successful vaccine combinations, such as diphtheria / tetanus/ whole-cell pertussis (DTwP) (Usonis V et al 1997), measles-mumps-rubella (MMR) vaccine and trivalent inactivated polio vaccine (IPV). New combinations are listed in Table 1.
Table 1: New
Combination Vaccines
|
Vaccine |
Combinations |
|
HBV-HAV |
Hepatitis
B virus Hepatitis A virus |
|
HBV-Hib |
Hepatitis
B virus Haemophilus influenza type b |
|
DTwP-IPV |
Diptheria
tetanus whole cell pertussis Inactivated poliovirus |
|
DtaP-IPV-Hib |
Diptheria
tetanus acellular pertussis Inactivated poliovirus Haemophilus
influenza type b |
|
DTwP-HBV |
Diptheria
tetanus whole cell pertussis Hepatitis B virus |
|
MMR-V |
Measles
mumps rubella Varicella |
Conjugate Vaccines
In conjugate vaccines, covalent coupling of polysaccharide antigen to carrier protein can improve the immunogenic response.
Haemophilus influenza type b conjugate is the currently licensed vaccine (Hib). The major approach to prevention of Haemophilus type b disease is active immunization with purified capsular PRP (polysaccharide). The use of a conjugated vaccine (a combination of H. influenzae type b PRP with diphtheria toxoid or N. meningitides outer membrane protein) has been remarkably successful in reducing both type b disease and colonization (Deodhare SG, 2001). Several conjugate pneumococcal vaccines are currently in development (Polan G 1999).
The current typhoid vaccines confer only about 70 percent immunity, do not protect young children and are not used for routine vaccination. A newly devised conjugate of the polysaccharide of Salmonella typhi Vi bound to nontoxic recombinant Pseudomona aeruginosa exotoxin A (rEPA) has enhanced immunogenicity in adults and in children 5 to 14 years old and has elicited a booster response in children 2 to 4 years old (Lin FYC et al 2001).
Typhoid Vi Conjugate Vaccine
The capsular polysaccharide of S. typhi Vi is both an essential virulence factor and a protective antigen. Like most polysaccharide vaccines, the Vi vaccine does not induce either protective levels of antibodies in young children or a booster response. To overcome the limitations of the age-related and T-cell-independent immunogrnicity of the vaccine, the same strategy was used as for the Haemophilus influenzae type b polysaccharide vaccine. Vi was bound to a nontoxic recombinant protein that is antigenically identical to Pseudomonas exotoxin A (rEPA).
The researches (Lin FYC et al 2001) enrolled more than 11000 children aged 2-5 years from a region in Vietnam where typhoid is endemic into a double blind trial. The children were randomized to receive either a saline placebo or the new vaccine (Vi-rEPA vaccine), as two injections six weeks apart. They were followed for 27 months.
Among children who received both doses of the vaccine, only four cases of typhoid fever developed (4/5525). In contrast, 47 of the 5566 children who received two doses of placebo developed typhoid.
The new (Vi-rEPA) produces a good immune response, is well tolerated and is effective in protecting young children from typhoid.
References
DNA Vaccines
1. McDonnell WM, Askari FK (1996). DNA vaccines, N Engl J Med 334: 42-45.
2. Seder RA, Gurunathan S (1999). DNA vaccines Designer vaccines for the 21st century. N Engl J Med 341: 277-278.
Combination Vaccines
1. American Academy of Pediatrics (1999). Combination vaccine for childhood immunization, Pediatrics 103: 1064-1077.
2. Usonis V et al (1997). Feasibility study of a combined diphtheria -tetanus- acellular pertussis hepatitis B (DPTa-HBV) vaccine. Vaccine 15: 1680-1686.
Conjugate Vaccines
1. Deodhare SG (2001) Vaccines and immunizations. In General Pathology and Pathology of Systems, 6th Edn. Vol. 1 pp. 538-542 and pp 856-857. Popular Prakashan, Mumbai.
2. Lin FYC et al (2001). The efficacy of a Salmonella typi Vi Conjugate vaccine in two-to five year old children. N Engl J Med 344: 1263-1269.