More effective vaccines

Polio, smallpox and measles are some of the horrors humanity experienced and, thanks to the vaccines; they are now just ghosts of the past. Nevertheless, and in spite of the success of this prevention method, countless investigations have been made to cure new diseases, improve its efficiency or reduce the associated risks, among others. It is precisely on this field that a group of scientists are conducting a study. The team consists of researchers and fellows of the Clinical Biochemistry and Immunology Research Centre (CIBICI, CONICET-UNC) and the Research and Pharmaceutical Technology Development Unit (UNITEFA, CONICET-UNC).

The vaccines comprise two parts. The first one contains the antigens, that is to say, one part of the microorganism that causes the disease, which the researchers try to develop an immune response against. Some vaccines have these microorganisms attenuated, others have it inactivated and, finally, there is a third group called ‘subunit vaccination’, made up of small parts of those organisms. The first ones are very effective but they might pose a risk to the patient’s health. The last ones are easier to produce, less expensive and more secure but the response is poor. It is here that the adjuvants, which are the other component of the vaccines, become important and that is why the team studies them.

The experiments are conclusive on the matter. A vaccine composed of a known model antigen and an adjuvant called CpG-ODN. Two groups of mice were used: one was immunized with this combination and the other one with a formulation where CpG-ODN was added to a structure of liquid crystal structure called coagel. Thus, the researchers observed that this last combination enhanced the adjuvant capacity of the CpG-ODN.

“We obtained a greater number of specific antibodies against the antigen and increased cellular response in cytokine production, proteins that help to strengthen the response of other immune system cells”, María Fernanda Sánchez Vallecillo, CONICET postdoctoral fellow at the CIBICI, explains. These results were published in Biomaterials magazine.

Apart from that, other relevant properties of the vaccine production were analyzed. The first one is that it should be economical and, as the coagel enhances the adjuvant, half of the CpG-ODN doses could be used by reducing the cost. This is also beneficial to the body because in spite of the fact that it has not been reported as toxic, it reduces any possible side effect. Besides, another significant point is that the coagel allows keeping the effect of the strengthening of the response at least up to six months in mice, what represents a third of their lives.

“The coagel has the possibility of ‘wraping up’ substances so that they are not massively in contact with the body. This could collaborate by reducing the stability problems the CpG-ODN has when in contact with different elements of the body that either break it or eliminate it. So, probably, this protection could be one of the mechanisms that favor the strengthening of the adjuvant effect”, Santiago Palma, CONICET independent researcher at the UNITEFA, describes.

How was its development?

The adjuvant has the role of increasing the effect of the antigens. Over one hundred years of this component, only three substances were approved to have this role: aluminum salts, oil-in-water emulsions and a ligand of innate immune receptor. The incorporation of a new molecule becomes difficult because of the need to be effective and secure of the patient’s health. “This means that the undesirable effects should be minimum and localized. Furthermore, they should not cause general toxicity and, above all, it cannot generate an autoimmune response”, Sánchez Vallecito affirms.

The CIBICI team has been investigating CpG-ODN, a DNA with high concentration of the cytosine-guanine nucleotide pair. Although it worked properly, as the antigens were purer, it lost the effectiveness. “At this point we started to interact with the UNITEFA group, who was working with coagel, and we thought that by joining the CpG-ODN and the coagel we would be able to get a good response”, Maletto comments.

That is how the developments of Palma group and Daniel Allemandi, CONICET principal researcher at the UNITEFA, got involved. “We work on the design of platforms to convey drugs or bioactive substances such as the CpG-ODN case, whose activity is limited by different problems of stability, low efficiency among others. The aim is to enhance its performance”, Palma explains.

For more than ten years, the researchers have worked with coagel, which is used to solve efficiency problems of different molecules. “The first hypothesis was that by combining our knowledge on CpG-ODN- including its possibilities and problems- with our information on coagel, we could develop an application to strengthen the effect of the first one. And that is how it was”, Palma concludes.

For Palma, when the CpG-ODN is inside the structure of the liquid crystal, and at the time of its interaction with the other biological means, the release could be delayed. Consequently, this can positively impact, something that was demonstrated in vitro.

Finally, the scientists highlight that one of the most favorable points of this study is the collaboration between the two groups who were investigating different issues and met to work together. “From the correlation on, very positive things were developed. It is a good experience to collaborate with foreign teams but this study is 100% from Córdoba”, Maletto concludes.