The future of vaccines for infectious diseases

In concert with sanitation and clean water supplies, vaccination has been the most cost effective means of preventing infectious diseases.

Most vaccines have been inexpensive, easy to administer (albeit objected to by the recipient’s arm!), safe and effective. From when I was a child until today the number of new vaccines has multiplied dramatically. This will only continue at an accelerated pace in the coming years. In the future many more infections will be prevented; there will be a need for fewer shots as new approaches like patches and nasal administration are perfected; only a single dose will be needed as newer adjuvants are developed; DNA vaccines will come to the forefront; and there will be a plethora of new vaccines for chronic illnesses such as Alzheimer’s, atherosclerosis and diabetes type 1. These next few years will be very exciting as the science matures and current and pending clinical trials reach conclusions.

Vaccinations began with the pioneering work of Jenner in the late 1700’s. Smallpox was a serious disease with high morbidity and mortality but Jenner noted that milkmaids rarely got smallpox. They did get cowpox and this left their faces damaged, but it appeared that perhaps the cowpox was preventing smallpox by developing some type of bodily defense. So he took the fluid from a cowpox lesion, placed it on a young boy’s arm and scratched it with a needle. This crude preparation worked and it is essentially what was used until a few decades ago as the smallpox vaccination and what would be used again if an act of bioterrorism let this disease loose again.

By the late 1800’s, as bacteriology came into being, Pasteur and later others developed the first live attenuated bacterial vaccines working first with anthrax. Inactivated whole killed bacterial vaccines followed for cholera, typhoid and plague and were each used for over 50 years. The first viral vaccine was developed by Pasteur for rabies. Although he could not culture the virus, he was able to take the infected spinal cord of a rabbit, inoculate another rabbit, take its spinal cord and inoculate another rabbit, etc until after multiple passes and then two weeks of desiccation, the virus was attenuated yet still immunogenic enough to serve as a vaccine. The first subunit vaccines were diphtheria and tetanus toxoids. First it was found that broth cultures of Corynebacteruim diphtheriae and Clostridium tetani, when filtered, had a substance that was toxic to animals and which mimicked human disease. From these came the development of antitoxin vaccines.

Since then a large number of vaccines against infectious agents have been developed such as diphtheria, tetanus, pertussis (the DPT vaccine); measles, mumps and rubella (MMR); chickenpox; Hemophilus type b (a common cause of middle ear infections and meningitis in kids); pneumococcus (a common cause of pneumonia in adults and middle ear infections in children;) and of course the influenza vaccine.

We tend to forget that these were (and are) serious illnesses. Call many of them the common diseases of childhood, but large numbers died of measles, and all too many lost their hearing even if treated promptly with antibiotics for Hemophilus meningitis. Influenza still hospitalizes more than 100,000 Americans every year and leads to death in about 36,000 per year. At least 50% of flu cases could be prevented with vaccination – the key is to actually get vaccinated. The same can be said of polio. Americans tend to think of it as an eradicated disease but it still exists endemically in a few developing countries where vaccination has been either too expensive or thought to cause harm.

Do your kids need to be vaccinated now given that there are no cases in the United States? Yes, because the virus is just a jet plane trip away. Right now measles is a significant problem. Most kids get vaccinated and schools require proof of vaccination for entry. But some kids do not get vaccinated, especially home schooled children. And that proved to be a serious problem a few years ago when a homeschooled, unvaccinated teenager came back for a vacation in Romania in the prodrome of measles. She went to a church function on the weekend mingling with about 500 people including many other unvaccinated children. Thirty four individuals developed measles, 12 of whom needed hospitalization and one nearly died. Measles is simply not a “minor” childhood infection of little import. Nor are the others that can be prevented today with vaccination.

There are some very effective new vaccines for preventing infections. The pneumococcal vaccine is very effective in preventing this cause of pneumonia in adults. A variant vaccine called protein conjugate pneumococcal vaccine recently became available for children and infants. It has been very effective in reducing the frequency of bacteremic pneumonia and meningitis. It has also reduced the frequency of nasal carriage and of carriage of resistant strains. And since the children are protected, it tends to carry over to the adults in that they are less likely in household settings to acquire these strains of pneumococci.

Rotavirus causes diarrhea in infants and young children. Most kids develop it in the first few years of life and it can be quite debilitating. About 2 million children are hospitalized worldwide for rotavirus-induced diarrhea and about 600,000 die each year, the latter mostly in developing countries. The new vaccines developed by Merck and Glaxo are very effective with better than 90% protected and with a 95% reduction in hospitalization and ER visits.

Herpes zoster (shingles) is common as we age with a life time incidence after age 60 of about 20%. It is caused by the varicella-zoster virus which has lain dormant in dorsal nerve root ganglia since infection in childhood with chickenpox. It is also common in immune compromised individuals and is quite frequent following radiation for Hodgkin’s disease. The new zoster vaccine from Merck prevents about one half of cases in those over 60 and the remainder have less severe infections. So it is a very worthwhile vaccine to get.

Other new vaccines will come soon for infectious agents and we can expect that the fields of molecular biology, biotechnology, DNA recombination and genomics will play a large role in their development. So too will new approaches to administration, routes of administration, and adjuvants to boost immunity and allow for fewer doses. The hepatitis B vaccine is an example – and the first – of using recombinant DNA technology. An earlier vaccine was developed from a 22nm particle of the S antigen obtained from the plasma of hepatitis B carriers. It was effective but very time intensive to produce, taking some 65 weeks for inactivation, and hence expensive. Subsequently the S antigen was cloned in yeasts and the resultant derived antigen and the vaccine was thus much faster and less expensive to produce.

An important question is whether the research and industry leaders will continue to pursue vaccines against the most common causes of infectious illnesses or whether they will focus instead on those that will reap the most revenue and profit?

Stephen C. Schimpff is an internist, professor of medicine and public policy, and former CEO of the University of Maryland Medical Center. He is the author of The Future of Medicine — Megatrends in Healthcare and blogs at Medical Megatrends and the Future of Medicine.