History of vaccination.

Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.

Influenza vaccines: from whole virus preparations to recombinant protein technology.

Vaccination against influenza represents our most effective form of prevention. Historical approaches toward vaccine creation and production have yielded highly effective vaccines that are safe and immunogenic. Despite their effectiveness, these historical approaches do not allow for the incorporation of changes into the vaccine in a timely manner. In 2013, a recombinant protein-based vaccine that induces immunity toward the influenza virus hemagglutinin was approved for use in the USA. This vaccine represents the first approved vaccine formulation that does not require an influenza virus intermediate for production. This review presents a brief history of influenza vaccines, with insight into the potential future application of vaccines generated using recombinant technology.

From brain passage to cell adaptation: the road of human rabies vaccine development.

A major challenge for global rabies prevention and control is the lack of sufficient and affordable high quality vaccines. Such candidates should be pure, potent, safe, effective and economical to produce, with broad cross-reactivity against viral variants of public health and veterinary importance. The history of licensed human vaccines reviewed herein demonstrates clearly how the field has evolved to the current state of more passive development and postexposure management. Modern cell culture techniques provide adequate viral substrates for production of representative verified virus seeds. In contrast to outdated nervous tissue-based rabies vaccines, once a suitable substrate is identified, production of high titer virus results in a major qualitative and quantitative difference. Given the current scenario of only inactivated vaccines for humans, highly cell-adapted and stable, attenuated rabies viruses are ideal candidates for consideration to meet the need for seed viruses in the future.

Whole cell vaccination for meningococcus: Lessons from an idea whose time has gone.

Endotoxin in vaccines has long been recognized as a cause of adverse events and is generally regarded as a contaminant. However there are now a number of vaccine candidates that contain endotoxin as either antigen or adjuvant, particularly vaccines for Neisseria meningitidis based on native outer membrane vesicles (NOMV). Vaccines containing meningococcal endotoxin are not new. From 1907 to 1939 approximately 400,000 individuals were immunized with whole cell vaccines against meningococcus. We reviewed reports of meningococcal vaccinations from this period to characterize the adverse events in order to draw a baseline for evaluating meningococcal NOMV vaccines. The majority of these investigators conclude that whole cell vaccination was well tolerated with an adverse event profile comparable to other whole cell vaccines for Gram negative pathogens. There is insufficient data to draw conclusions on the duration of protection, if any, induced by whole cell meningococcal vaccines.

Evolution, benefits, and shortcomings of vaccine management.

BACKGROUND: The reduction of childhood mortality by vaccines has been one of the greatest public health successes of the past century. However, many targets for immunization remain uncontrolled, and new or improved vaccines are emerging to meet these challenges. OBJECTIVE: To review the evolution of vaccination and take an objective look at current vaccine development technologies, thereby framing the discussion of vaccine management. SUMMARY: The genesis of vaccinology is generally considered to have been a direct result of the observation that persons who had contracted smallpox rarely developed a second case. From this observation, the concept of variolation was born, which involved the inoculation of uninfected individuals using material collected from smallpox lesions with the goal of inducing immunity to future infection. The use of attenuated, live virus to induce immunity was the next step in the evolution of vaccinology, followed by inactivation of the virus when diseases caused by organisms not amenable to attenuation were targeted. More recently, a variety of adjuvant strategies have been developed to improve the immunogenicity of inactivated vaccines, and genetic engineering has been employed to increase the safety, reduce the reactogenicity, and improve the immunogenicity of different vaccines. CONCLUSION: Clinical (efficacy and safety) and economic (cost and profit) considerations are competing priorities that need to be reconciled within a discussion encompassing the government, the public, the pharmaceutical industry, third-party payers, and private individuals or companies who administer these vaccines.

[On three revolutions of vaccine].

Since the Chinese inuented the uaniolation with human pox vaccine and Jenner invented the vaccine for cowpox, the great achievements of vaccination in preventing and treating many diseases are universally acknowledged. In 1995, the New York Academy of Sciences of America sponsored a symposium on DNA (deoxyribonucleic acid) vaccine, which is called the third revolution of vaccine and new epoch for vaccinology. The first revolution was the invention of inactivated vaccines and live attenuated vaccines represented by Pasteur at the end of the nineteenth century. The second one was the subunit of vaccine prepared by DNA recombination technique and techniques of protein chemistry in 1980s.

Live attenuated vaccines against influenza; an historical review.

Live attenuated vaccines administered directly to the respiratory tract offer the promise of providing more effective immunity against influenza than subunit or split inactivated vaccines. Evidence has accumulated in recent years that immunological responses relevant to both the prevention of and recovery from influenza are best induced by natural infection. The ease with which the genes of influenza viruses reassort when two or more viruses infect a single cell has been exploited as a means of rapidly producing attenuated vaccines. Donor strains that have been shown by extensive testing to be fully attenuated are used to co-infect cells with contemporary epidemic strains to produce reassortants with the required degree of avirulence and the surface antigens of the epidemic strain. Reassortants prepared from cold-adapted mutants of both influenza A and B viruses have been widely shown from clinical trials in both the United States and Russia over many years to be well tolerated in both adults and children and to be highly efficacious.

Pneumococcal otitis media and pneumococcal vaccines, a historical perspective.

Although pneumococcal otitis media was recognized in the 19th century, the illness stimulated little interest in prophylaxis until recently. Whole cell vaccines of killed pneumococci, developed to prevent pneumonia, were replaced by vaccines of capsular polysaccharides following demonstration of their antigenicity in adults. Failure of the latter to stimulate antibodies in infants and young children and demonstration of the efficacy of capsular polysaccharide-protein conjugate vaccines in preventing infection with Hemophilus influenzae type b has led to the development of polyvalent pneumococcal polysaccharide-protein conjugate vaccines. Preliminary studies have shown them to be highly effective in preventing invasive pneumococcal disease in the first 2 years of life, and studies of their impact on otitis media are currently in progress.

Hepatitis and hepatitis A vaccine: a glimpse of history.

Human hepatitis has been recognized since the dawn of recorded history, but proof of infectious etiology and delineation of hepatitis A (infectious hepatitis) from hepatitis B (serum hepatitis) were not established until the first half of the present century. Development of the present killed hepatitis A vaccine depended on a series of breakthrough discoveries made during the last 25 years. These were marmoset propagation (1967); definition of virus attributes (1974-1975); development of diagnostic tests and seroepidemiology (1974-1975); and the preparation and proof of efficacy of a prototype killed hepatitis A vaccine (1976). Successful cultivation of hepatitis A virus in cell culture in 1979 quickly led to development of both live and killed hepatitis A vaccines for tests in human beings (1980-1990). The year 1991 marks the initiation of protective efficacy trials of two different killed virus vaccines in human beings. The safety and protective efficacy of the first vaccine (Merck) is reported in this symposium and the findings in tests of a second vaccine (SKB) are awaited. Hepatitis A is clearly a conquerable disease, initially in its elimination as an important disease entity and eventually in its eradication.

Virus inactivation: lessons from the past.

The organizers of this meeting have assigned two tasks to me. The first is to describe the state of affairs in 1955 when several lots of Salk poliovaccine, which had been formalin-inactivated according to government regulation and had been released for use in children, were subsequently found to have retained a small amount of live virulent virus. The second task is to describe a series of experiments that we conducted 25 to 35 years ago on the influence of cations on the thermostability of viruses. Perhaps there are some lessons to be learned and some benefits for future research to be gained from this history.