Viruses, like living beings, undergo constant evolution. Some of these can exchange genetic matterial to form new viruses, and although not all are a threat to humans, some of them can be deadly. The best known way to deal with these pathogens is vaccines.
Currently the development of vaccines involves weakened or attenuated viruses that do not cause any disease but their administration serves for the body to generate an immune response to auto-protect against a subsequent infection. There are several ways to produce vaccines: using embryonated eggs, cells in culture, and through the generation of viruses or recombinant proteins, for example.
However, there is a research group led by Dr. Fernando Esquivel Guadarrama, of the Faculty of Medicine of the Autonomous University of the State of Morelos (UAEM), that proposes a new and different concept for the development of vaccines against the influenza and rotavirus viruses.
From a molecular approach, Esquivel Guadarrama, doctor in immunology from Brunel University, England, and colleagues explore the possibility of using antigens or proteins of the aforementioned viruses that do not mutate. Viruses are composed of external and internal proteins. Unlike most external proteins –which can vary according to the environment, mutate and create viruses that are more resistant to vaccines– internal proteins and some external proteins mutate little. However, they do not induce a vigorous immune response.
Influenza viruses are pathogens that cause around 290 of them each year to more than 600,000 deaths worldwide, according to data from the World Health Organization (WHO). These viruses have constant antigenic changes and, therefore, the antibodies that allow the human body to generate an immune response are not efficient when the virus changes or mutates. This property of antigenic mutation hinders the development of vaccines against all circulating strains of influenza or against new strains such as those that cause pandemics.
Influenza virus strains change every year and can gradually evolve through mutations in genes that are related to viral surface proteins: hemagglutinin and neuraminidase. These mutations can cause the outer surface of the virus to appear different from a host previously infected with the virus’s predecessor strain.
According to Dr. Esquivel Guadarrama, all strains of the influenza virus have a membrane protein called M2 that has very few changes in its sequence and, therefore, could be useful in the development of a universal influenza vaccine if its immunogenic capacity was not so poor.
The research work carried out in the Viral Immunology Laboratory of the Faculty of Medicine of the UAEM aims to strengthen the immunogenicity of antigens (proteins) that do not mutate to generate protection against these viruses, as is the case of the protein M2.
The researcher explained that they make these proteins or regions that are not very immunogenic to generate that characteristic. “With this we will ensure an immune response against all existing strains and even against those that we do not yet know,” Dr. Esquivel Guadarrama said.
The objective of this line of research, she said, is the generation of totally heterotypic or crossed vaccines, and to have a vaccine against all strains of influenza or rotavirus, depending on the case, with a single antigen.
Besides being an innovative proposal, according to the UAEM academic, it would be economically viable because this would stop the need of developing vaccines every time a new viral threat is presented by influenza or rotavirus.
“For example, instead of using several strains of rotavirus for a vaccine, we use an antigen that covers all rotavirus that are circulating and those that are going to emerge,” he explained.
Rotavirus is a pathogen that causes deaths from gastroenteritis in infants. It infects and destroys the enterocytes of the small intestine, which leads to severe vomiting and diarrhea requiring hospitalization and, if not well cared for, can lead to death.
Although formed by different types of proteins, VP6 is the most abundant protein in the virus, which constitutes approximately 50 percent of the total protein of the structural unit of the virus.
Esquivel Guadarrama shared that VP6 is the most antigenic and abundant rotavirus structural protein, and its T lymphocytes interfere with the rotavirus replication cycle, making it a viable candidate to be used in the development of a vaccine.
“The problem is that when a vaccine against rotavirus is made, all the strains that infect humans must be included, so that the immunity of the individual’s antibodies is effective against all strains that circulate. We have evidence that our vaccine concept can work. For influenza, the antibodies are the ones that generate protection; but in the case of rotavirus, it is the T cells that generate a protective immune response,” he said.
Finally, researcher Fernando Esquivel Guadarrama said that this concept of “universal” vaccines is the goal of several laboratories in other parts of the world, and even research is already been carried out with the human immunodeficiency virus (HIV) with a view to protect against a large number of variants of this virus.
Source: Agencia Informativa CONACYT