Researchers from HZI vaccine department have discovered a small molecule c-di-IMP which leads to a strong immune response and it is significantly more effective than known adjuvants. Adjuvants boost the bodies immune response to vaccines. the new molecule appears to help with nasal sprays, which could allow prevention of infection and not just resistance.
The adjuvants present in vaccines have a bad reputation. For most people, they are only unnecessary compounds within a medicinal product. This is a misunderstanding since adjuvants have a critical impact on the success of a vaccination. In the best case scenario, one single vaccination shot would be now sufficient for conferring life-long protection. The researchers have now found a new molecule with the capacity of improving responses to vaccines. The synthetic compound, the so-called c-di-IMP, might be more than just a potent vaccine enhancer. The scientists expect to create new vaccination strategies based on c-di-IMP. The group’s results have now been published in the current issue of the scientific journal “Vaccine”.
The immune system often reacts only weakly to the attenuated pathogens or their fragments present in a vaccine. Thus, partial or short-life protection is usually stimulated. The adjuvants by themselves do not trigger an immune reaction, but given as components of a vaccine, they modulate and enhance the immune responses elicited, thereby providing a stronger, early and long-lasting protection. While searching for new adjuvants, the vaccine researchers at the HZI have now found the molecule “c-di-IMP”.
“With this new adjuvant, we want to improve already existing vaccines, such as those against influenza or hepatitis. Maybe it also helps to create new vaccines using component that in the past did not promote efficient immune responses using known adjuvants.”
“The molecule might also help us to develop new vaccination strategies,” says Professor Carlos A. Guzmán, head of the “Vaccinology and Applied Microbiology” Department at the HZI. His department is working on an alternative to the “shot”: the snuff vaccination. Here, the vaccine is taken as a nasal spray to work where most pathogens enter the body: at the mucosae. Guzmán highlights, “c-di-IMP enhances also local mucosal immune responses, representing a strong candidate for the implementation of such type of vaccines. This is very important because mucosal vaccines can prevent not only diseases, but also to block infections before they even take place, thereby protecting also non vaccinated contacts against disease.”
Here we demonstrated that bis-(3′,5′)-cyclic dimeric inosine monophosphate (c-di-IMP) exhibits potent adjuvant properties. BALB/c or C57BL/6 mice were immunized with the model antigens beta-galactosidase (β-Gal) or Ovalbumin (OVA) alone or co-administered with c-di-IMP by the intranasal route. Animals receiving c-di-IMP showed significantly higher anti-β-Gal or OVA immunoglobulin G titres (IgG) in sera than those vaccinated with β-Gal or OVA alone. Furthermore, strong local immune responses were also detectable in different mucosal territories, as shown by the high levels of β-Gal-specific secretory IgA (sIgA). The analysis of the antigen-specific IgG isotypes in sera, together with the profiles of the cytokines and chemokines secreted by lymphocytes from vaccinated animals showed that the use of c-di-IMP resulted in stimulation of a mixed TH1/TH2/TH17 response. Mucosal immunization of C57BL/6 mice with OVA using c-di-IMP as adjuvant also led to the stimulation of both humoral and cellular (i.e., 60% of antigen-specific lysis by in vivo CTL) responses. Our results demonstrated that the novel compound c-di-IMP exhibits strong adjuvant properties when co-administered with an antigen by the mucosal route, thereby representing a promising candidate adjuvant for the development of mucosal vaccination strategies.
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