Vaccines Then, Now, and Coming Soon

Much is in store in the fight against infectious diseases in this century

By Lucio Victor Jr.

Vaccine development in the past century ushered in immense changes in the health and well-being of humanity. In the past two decades alone, new discoveries and improved techniques have generated newer vaccines and inspired a quest to broaden the disease coverage of vaccines. On the other hand, many issues involving vaccines that preoccupied science and medicine early in the past century reverberate until now.

    Vaccines are known to generate an immune response by mimicking the actual inoculation of a disease-causing pathogen. This passive form of immunization may pass unfelt by the vaccine recipient except for the uncomfortable needle prick. But in a few cases, some vaccines are known to generate a quasi-illness where the patient may experience at most mild to moderate fever, pain at the vaccination site, or malaise, and rarely headache, dizziness, or nausea.

    Advances in molecular biology and biotechnology have painfully tried to create vaccines that enhance a very good immune response, have fewer to no side effects, are stable, and can be easily mass produced. Although no vaccine has actually come close to perfect, many vaccines are available now in the market against a vast array of pathogens.

Mimic

    Conventional vaccines used today are made by one of several means. Inactivated vaccines are made from live pathogens that have been killed by heat or immersion in formalin. As the killed organisms in these vaccines are inoculated into a patient, an immune response is mounted, mainly against the antigens appearing on the surface of the dead organism. The next time a similar pathogen invades the body, antibodies would fight it.

    Live attenuated vaccines are also made up of live organisms that incite an immune response. But these are incapable of causing an actual infection in the patient. The organisms in these vaccines are capable of replicating in the host, closely mimicking what happens when an actual infection takes place. The organism can be attenuated by passing the virus through animals like rabbits, horses, and monkeys; by deleting the genes responsible for its virulence; or by rearranging the genetic sequences that code for virulence factors.

    Although both consist of whole viral or microbial cells, inactivated vaccines are safer because these are made up of dead organisms that cannot mutate or revert to their virulent form. However, these require booster doses because they do not incite an immune response as heavily as live attenuated vaccines do. Attenuated vaccines, on the other hand, may cause disease or an adverse reaction in persons who are immunocompromised or have an immunodeficiency. These vaccines are also less stable and require refrigeration.

    Vaccines against cholera, pertussis (whole cell) and bubonic plague are inactivated. Vaccines against typhoid fever, measles, mumps, German measles, chicken pox and herpes zoster, yellow fever, hepatitis A, rabies, tuberculosis, and smallpox are live attenuated. Vaccines against influenza, polio, and Japanese encephalitis are both live attenuated and inactivated.

    Toxin-based vaccines, like those for tetanus and diphtheria, are made from actual exotoxins or pathogenic organisms that have been processed so that they do not cause disease in the host while inducing antibody formation. Some manufacturers add surface antigens from the actual organisms so that the host can also produce antibodies against the organism that produces the vaccine. Vaccines from surface antigens are made by genetic modification. These subunit vaccines can also elicit an immune response with limited side effects. Vaccines against pertussis (acellular), tetanus, hepatitis B and lyme disease are examples.

Novel Armamentarium

    The 21st century ushers in novel changes in vaccine development, says University of Pennsylvania's Prof. Stanley Plotkin. Vaccine laboratories would soon turn out not only with fine-tuned versions of present-day vaccines but also new vaccines that are easier to administer, have fewer side effects, enhance a greater immune reaction, and can be administered in combination with other vaccines.

    More attention is now being focused on recombinant vector vaccines that use an inert virus or bacterium that has been genetically modified to contain the antigens but not the virulent characteristics of the pathogen they are supposed to mimic. These can be administered transcutaneously.

    As of now, most vaccines are administered orally or injected intramuscularly or subcutaneously. Recombinant vector vaccines can make administration as simple as a sniff or a scratch on the skin.

    Also being developed are peptide and DNA vaccines. Peptide vaccines enhance the encoding of portions of the surface antigen on the attenuated vector virus. DNA vaccines utilize genetically modified bacteria to produce a genome that would contain a sequence-that incorporates into the host-for the creation of antibodies. These vaccines may be administered by injection or intranasally.

Developments

    Topping the list of vaccines that may soon be in the market is one against rotavirus, the leading cause of diarrhea that leads to severe dehydration in children. Dr. Plotkin says that the current prototype is a genetic reassortment containing four different serotypes of the rotavirus combined into one attenuated donor virus.

    Also undergoing development or clinical trials are vaccines for respiratory syncitial virus (RSV), shigella (dysentery), enterotoxigenic Escherichia coli (ETEC), HIV/AIDS, malaria, schistosomiasis, and dengue. RSV infection leads to susceptibility to Streptococcus pneumonia and Haemophilus influenze and causes about one million deaths yearly. The first vaccine developed for RSV was a formalin inactivated whole cell vaccine. Then came a live attenuated type and a subunit vaccine using surface antigens.

    Shigella, also a leading cause of mortality secondary to diarrhea and dehydration, kills about 3.5 million people annually, mostly children. Injectable polysaccharide conjugate vaccines and live attenuated oral vaccines against the common serotypes-S. dysenteriae, S. flexneri, and S sonnei- are under testing.

    ETEC kills 300,000 to 700,000 people yearly, mostly children under five. An oral recombinant vaccine is underway. It is programmed to create antibodies that inhibit attachment of ETEC on the gastrointestinal villi lining the intestines. Another live-attenuated vaccine is also being developed.

    The sexually and transfusion transmitted HIV/AIDS virus is also being subjected to tests using recombinant subunit vaccines that incite the creation of antibodies against the surface antigens of the virus. But there has not been much success.

    A prototype tetravalent live attenuated vaccine effective against all four strains of the dengue virus has undergone phase I and II clinical trials and is undergoing the final stages of phase III at the Mahidol University in Thailand.

    At least six vaccines are currently undergoing development for Schistosoma japonicum, which causes severe irreversible liver damage, and its close relatives, S. hematobium and S. mansoni. The vector borne malaria that has plagued humanity for ages claims 1.5 million people yearly, 90 percent of them from the African continent.

    Four protozoans figure in the disease-Plasmodium falciparum, P. vivax, P. malariae and P. ovale. A candidate vaccine that blocks the development of the disease is being worked on. In May 1995, Dr. Manuel Patarroyo, one of the leading experts on the malaria vaccine granted the World Health Organization an exclusive royalty-free license to the patent and know-how of his candidate vaccine.

    With vaccine development shifting to high gear, preventing more infectious diseases may not be far away. The time will come when only one dose of the vaccine would be enough to confer lifelong immunity, and booster doses would be a thing of the past. Combination vaccines would become commonplace, which would mean fewer injections or administrations. Vaccine patches and spray may also soon replace injectables.