For nearly a hundres now, vaccines have been the best defence against all viral threats
DURING the 20th century, vaccines for bacterial toxins and many common acute viral infections were developed and made widely available. There are currently 30 vaccines that are mainly given prophylactically to prevent or minimize diseases by agents infectious to human.
Vaccines have changed the face of viral disease as much as antibiotics have affected the course of bacterial disease. Depending on their preparation mechanisms, vaccines are of three types: live attenuated preparations, inactivated whole organisms or subunit preparations.
Evidence of the profound impact that vaccines have had on our daily lives is evident all around the world. The use of vaccines through mass immunization campaigns has reduced to minimal levels the common childhood infections that plagued societies around the world from the beginning of recorded history — measles, diphtheria, tetanus, polio, rubella and smallpox are, for most people, diseases that are encountered fortunately, only in the history books. These diseases are no longer the factors of everyday life that they once were and this is entirely due to the development of vaccines that are safe and effective. Indeed, just this year, a new, live, attenuated influenza vaccine was licensed for intra-nasal aerosol administration.
The pace with which new vaccines are being developed has increased. This increase is due primarily to the impact of the global investment in basic research, especially in molecular biology and immunology. New approaches to immunization have emerged from the results of this basic research that offer great promise.
One approach generating great interest is that of inducing protective immune responses by injecting engineered DNA sequences from infectious organisms against which protection is desired. If an antigen can be identified it is possible to insert the DNA sequence coding for the protein antigen into a carrier genome (such as several of the poxviruses or alphaviruses). Once delivered into the host, the organism (and hence the inserted DNA) undergoes limited replication, the protein of interest is produced, and the host develops an immune response against the protein.
In a related strategy, so called ‘naked DNA’ is injected directly into the host to produce an immune response. Naked DNA is simply a bunch of sequences of DNA inserted into bacterial plasmids (simple, extrachromosomal rings of DNA found in bacterial cells) and injected into the host. These have been effective in animal models, but intramuscularly injected DNA in humans has failed to generate vigorous immune responses, although transdermal or intradermal delivery of DNA has been more encouraging.
Development of optimal vector vaccines depends on the understanding of immune function and of how to achieve favourable specific perturbation of the immune system. Recombinant DNA vaccines are receiving intensive research investigation and are currently entering clinical trials. The collective attributes of non-replication, long-term stimulation, absence of antigenicity and elicitation of both humoral and cellular immune responses offers advantages over other vaccines and may predict a central role for DNA vectors in new era vaccinology.
These new approaches to immunization will make it possible to prevent many other infectious diseases. DNA vaccines as well as other technical innovations will transform immunization in the coming century. The major challenge is to think of new approaches for the introduction of these new vaccines, particularly in areas of the world where infectious diseases exact their highest toll, regions in which poverty is common place and medical care systems rudimentary. The solution of this problem is not a simple one and will depend on the development of global networks that can facilitate the translation of these research findings into practical reality. The science and technology systems of developing countries have characteristics that may facilitate the production of new and improved vaccines, better delivery systems and simplified immunization schedules.
Any new vaccine is to be tested for safety and immunogenicity and evaluated for protective efficacy and effectiveness. Safety testing is done in susceptible animals and volunteers with clinical, pathological and microbiological examinations. Immunogenicity studies include selection of immunological markers as possible correlates of vaccine protection, immune responses to different vaccine doses, persistence of immunological marker, rate of antibody decay, booster effect, adjutant effect, cross reaction to different vaccine subtypes, vaccination schedule and host factors influencing immune response.
The worldwide spread of HIV and the intense public interest in AIDS are unprecedented in the history of human diseases. Devastating effects of HIV infection are easily predictable, especially in developing countries. Vaccines are probably the only way to eradicate the virus and prevent AIDS in the long run. Recent findings provide some cause for optimism that vaccine development may be feasible and that HIV may be preventable and AIDS avoidable. Unconventional and even provocative approaches may be necessary as HIV is different in many aspects from other viruses against which vaccines have successfully been developed. Answering key biological questions and pursuing close collaborations among scientists from many different disciplines will be essential for the development of successful vaccines. Throughout the “vaccine continuum”, from disease surveillance and basic microbiogic research to the delivery of vaccines in the field, public and private sector organizations interact in very complex ways. Contributions from both the public and private sectors are essential to the success of any joint efforts to provide the protection of vaccines to populations at risk around the world. Neither sector can do the whole job alone. This interdependence of the public and private sectors, of governments and industry, of international organizations such as WHO and UNICEF and the multinational vaccine corporations is both a source of strength and a source of conflict. Great advances can be made when industry, governments and international organizations work in cooperation.
Interest has increased in biological weapons of mass destruction as terrorists look for methods with which to inflict harm on the greatest number of people, with the lowest possible cost and technology needs, while creating mass panic. While vaccines have been licensed against smallpox, plague, anthrax and others, only limited amounts of anthrax vaccine are being produced in the United States for specific risk groups. Limited and aging stockpiles of smallpox and plague vaccine are available but are insufficient for large numbers of people.
However, major obstacles in producing such vaccines for public use include the need for a financially viable market, the impossibility of conducting human efficacy trials, the intangible risk-benefit ratio at the public health level, and governments’ reluctance to face the reality of bioterrorism.
As advanced vaccines and vaccine technologies become available, massive public education efforts will be required to alleviate these concerns. This is particularly true for DNA vaccines, combination vaccines, vectored vaccines and vaccines administered in a parenteral depot fashion. The more distant potential for person-specific vaccines based on individual genotyping (vaccines against a specific malignancy in a specific individual) will also raise serious concerns. None the less, the prospect of both preventing and treating many serious diseases by the use of vaccines portends an exciting era in public health and vaccinology.
For nearly a hundres now, vaccines have been the best defence against all viral threats
