Toward future cross-protective vaccines?
Winter is approaching and millions of people will use this year's flu vaccine, different from last year's one, and only able to fight a few strains. Wouldn't be nice to use a vaccine able to fight a vast variety of bacteria? Two teams of U.S. researchers from the University of California at Santa Barbara (UCSB) and the University of Utah have collaborated to develop a cross-protective vaccine. They didn't target flu, but their future vaccine could protect against up to 2,500 strains of Salmonella. Anyway, don't expect your doctor to tell you to get a shot for such a vaccine anytime soon. The UCSB team is working on it for the last ten years and a real vaccine hasn't yet been still tested on humans. But read more...
This research project has been led at UCSB by scientist Douglas Heithoff who's working with Professor Michael Mahan in the Department of Molecular, Cellular, and Developmental Biology. On the photo above, you can see Heithoff (on the left) and Mahan showing their future vaccine in a UCSB laboratory. (Credit: UCSB) Here is a link to a larger version of this picture.
Here are two additional links showing that the UCSB team is working on this project for quite a while: UCSB lab discovers cross-protective vaccine (UCSB Press Release, December 5, 2001) and Douglas Heithoff Fights Salmonella (UCSB Grad News, Spring 2002).
And the Mahan research page describes why he decided to focus on cross-protective vaccines. "A major obstacle in vaccine development is that there are often many different isolates of a given pathogen that are proficient in causing disease, and vaccination against one strain may not elicit protection against another strain, or even a variant of the parental strain. This is a principal reason why protective immunity against some microbes may require annual vaccinations with different strains, why vaccine efficacy may depend on the specific pathogenic isolates endemic to a given geographical region, and why mutant variants can cause disease in populations that are immune to infection with the parental strain. Thus, it is desirable to develop bacterial vaccines that can stimulate cross-protective host immune responses to several pathogenic strains."
The UCSB team worked with a University of Utah team led by Elena Enioutina who worked with graduate student Diana Bareyan and Raymond Daynes, Professor of Pathology.
Here is a quote picked from a recent Mahan interview. "'Vaccines are great. Second to water sanitation, they are the best medical invention of mankind.' The problem with conventional vaccines is that they only protect against a limited number of closely related strains. 'That is why flu vaccines need to be administered every year because different flu strains arise every year.'"
Now, let's go back to the UCSB new release mentioned in the introduction. "The team focused on developing a vaccine against Salmonella, which causes food and blood poisoning –– with over 1.5 million cases in the United States each year. 'It's endemic worldwide,' Mahan said. 'It's not a carnivore issue –– it's everybody's issue since fruits and vegetables are often the source of infection.' By disarming a 'genetic switch,' the research team has developed a vaccine that protects against many strains of Salmonella. The new vaccine stimulates the production of antibodies and immune cells that work together to kill bacteria. Also, the vaccine does not induce a specific class of inhibitory immune cells that are known to contribute to immune declines in cancer patients. This lack of 'immune suppression' is an advantage of the new vaccine over conventional vaccines."
This research work has been published in the November edition of the journal Infection and Immunity under the title "Conditions That Diminish Myeloid-Derived Suppressor Cell Activities Stimulate Cross-Protective Immunity" (Volume 76, Number 11, Pages 5191-5199, November 1, 2008).
Here is the beginning of the abstract. "Immunity conferred by conventional vaccines is restricted to a narrow range of closely related strains, highlighting the unmet medical need for the development of vaccines that elicit protection against multiple pathogenic serotypes. Here we show that a Salmonella bivalent vaccine comprised of strains that lack and overproduce DNA adenine methylase (Dam) conferred cross-protective immunity to salmonella clinical isolates of human and animal origin. Protective immunity directly correlated with increased levels of cross-reactive opsonizing antibodies and memory T cells and a diminished expansion of myeloid-derived suppressor cells (MDSCs) that are responsible for the immune suppression linked to several conditions of host stress, including chronic microbial infections, traumatic insults, and many forms of cancer."
As you can see, these scientists have a very ambitious plan: fight many bacteria with a single vaccine, and even fight cancer. Will they succeed? Time will tell.
Sources: University of California at Santa Barbara news release, October 21, 2008; and various websites
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