Vaccines: Schooling The Herd

In Biologics, Biotech Basics, Clinical Trials, Drug Development, Mechanism of Action, The WEEKLY by Emily Burke

VACCINATION NATION

Back to school means shopping for new school supplies, adjusting to a new schedule, and making sure all required vaccinations are up to date.

Every state requires school-age children to be vaccinated against certain infectious diseases including tetanus, hepatitis B, measles, mumps, rubella, polio, pertussis (whooping cough), and chicken pox. Vaccination policies are highly effective at eliminating many types of sickness from the most perfect incubator — the classroom.

In this WEEKLY, we’ll go to the chalkboard to learn the basic science of vaccines.

BASIC SCIENCE

The idea behind vaccination is simple: by exposing someone’s immune system to a harmless version of a pathogen, we can train it to recognize and respond to the bug in the wild. After an initial exposure to a virus, our immune system creates memory cells which are then ever-ready to spring into action and attack the same disease later on down the line.

Vaccination is required because creating these pathogen-specific memory cells takes a few weeks — a length of time that is long enough for a virus to do serious damage to the body.

ABCs OF VACCINES

There are a few ways to create a vaccine and below we list the most common methodologies.

  • Inactivated vaccines: The most obvious type is the inactivated vaccines — the use of heat or chemicals to kill the pathogen. Inactivated vaccines produce a dampened immune response in comparison to other vaccine methods and often require “booster” shots. Inactivated vaccines include polio, influenza, and pertussis vaccines.
  • Live, attenuated vaccines: A live, attenuated vaccine simply means that the weakened (not killed) pathogens are unable to cause disease. Attenuation occurs by a process called “passage,” or growing viruses at temperatures slightly lower than the human body or in cells different from the human host cells. Under these conditions, the virus accumulates mutations that make it better able to survive in a new environment, but when injected into a human, it is no longer virulent. Attenuation may also be more direct and occurs when genes associated with pathogenesis or replication are removed in the lab. In general, attenuated vaccines induce a strong and long-lasting immune response. Examples of live, attenuated vaccines include measles, mumps, rubella, chicken pox, and polio.
  • Subunit vaccines: In some cases, just one protein from the virus can be enough to induce an immune response. These are called subunit vaccines and are typically made using recombinant DNA techniques to produce the desired protein. Advantages of subunit vaccines include easier production and a better safety profile for patients. Examples of subunit vaccines include pertussis and hepatitis B.
  • DNA vaccines: DNA vaccines are the next frontier in vaccine development. Rather than delivering a whole pathogen or pathogen subunit, DNA vaccines deliver just a gene. Once inside the body, the patient’s own cells reproduce the pathogenic protein. If successful, this technology would mimic a natural infection and elicit a strong immune response. The technical challenge that remains to be solved is the delivery of the pathogenic gene. Ichor Medical Systems (San Diego, CA) and Inovio Pharmaceuticals (San Diego, CA) are both developing electroporation-mediated DNA delivery systems to solve this problem.
TERM OF THE WEEK: HERD IMMUNITY

Herd immunity means a significant portion of a population has immunity to a particular pathogen. There is little opportunity for an outbreak, so even those who cannot be vaccinated such as immunocompromised individuals, pregnant women, or newborn babies are unlikely to become infected despite their unprotected state.

 A UNIVERSAL FLU VACCINE?

Unlike most other vaccines, you must get the flu shot every year in order to be afforded protection. Current flu vaccines work by mounting an antibody response against two large proteins on the surface of the virus — hemagglutinin (H) and neuraminidase (N). The catch? The structure of those two proteins changes every season due to a high mutation rate. Once the structure changes, the immune system no longer recognizes it, and the body must be retrained. This is also why the vaccine is only 60-70% effective — when formulating each year’s vaccine, scientists attempt to predict the influenza strains that will be circulating in winter, and they are seldom 100% correct.

For many years, scientists have talked of producing a universal flu vaccine. Recent advances in vaccine technology have led to some promising developments. BiondVax (Ness Ziona, Israel) has identified nine epitopes — short sequences of proteins that elicit an immune response — that do not vary much between different strains of the virus. These sequences were combined to make one recombinant protein referred to as Multimeric-001 (M-001). The hope is this combination of epitopes will invoke a strong immune response which will be protective over several flu seasons. M-001 is in Phase II clinical testing.

Researchers at Crucell Vaccine Institute of Janssen Pharmaceuticals (Leiden, Netherlands) have discovered an antibody that recognizes and binds a portion of the HA protein that doesn’t mutate very rapidly. Studies in animals suggest treatment with this antibody significantly reduces the amount of active virus present. Human clinical trials are in the works.

A clinically tested and FDA-approved universal flu vaccine is still years away, but these early results are promising. The new vaccine would most likely need to be administered every five or 10 years, rather than annually—but the real advantage will be its ability to protect against a range of different influenza strains, inching closer to 100% efficacy. And since most of us have suffered through a bad case of the flu, we can all agree that a universal flu vaccine cannot come soon enough!