Comparison of the CD4+ T cell and antibody responses to different Influenza vaccination regimens and to infection in naive and pre-exposed mice
Year: 2010
Type: dissertation
Abstract: Seasonal epidemics and the threat of a pandemic of influenza virus are a significant burden to public health, and therefore, improved vaccines that induce a broader and more potent immune response are needed to provide better protection. Formulation of vaccines with potent adjuvants is an attractive approach for enhancing the performance of vaccines composed of subunit antigens. In the present study we evaluated different adjuvants (MF59, CpG, E6020 and IC31) alone and in combinations for their ability to enhance and modulate antibody and CD4+ T cell responses induced by subunit influenza vaccines. As individual adjuvant, MF59 induces optimal cellular and humoral responses, whereas none of the tested immune-potentiators (CpG, E6020 or IC31) when administered as single adjuvant with the influenza vaccine are able to induce as high CD4+ T cell or antibody responses as MF59 does. On the other hand, MF59 is not able to induce effective Th1 responses, which could be achieved by the addition of an immune-potentiator. The addition of CpG to MF59 allows the induction of a potent Th1 response; also the combination of MF59 with E6020 and IC31 immune-potentiators results in a shift of the immune responses from a Th2- toward a more pronounced Th1-type, but in these cases the shift is less marked, maintaining a more balanced immunity. Thus, choosing the appropriate adjuvant combinations opens the possibility to drive and modulate the quality of the immune response into a desired direction. Further investigations on the protective capacity of a Th2 vs. a Th1 promoting Flu vaccine (adjuvanted respectively with MF59 adjuvant and MF59 + CpG) demonstrated that both types of adjuvanted vaccines induce levels of neutralizing antibody titres higher than those generated by exposure to sublethal doses of influenza virus, and both provide protection from lethal challenge with homologous influenza virus. However, pre-exposed mice exhibit minor weight loss than mice immunized with adjuvanted vaccines when challenged with a lethal dose of virus. Finally, the immune responses induced by different vaccine formulations in naïve mice were compared with those induced in mice previously infected with influenza virus, a situation more similar to that found in humans. In contrast to naïve mice, mice pre-exposed to influenza virus showed a clear Th1 response to MF59, suggesting that the pre-established immune status influences the outcome of vaccination. Our investigations have significant implications for the development of new and improved Flu vaccines against pandemic and inter-pandemic influenza virus strains. They offer the opportunity to establish which type of immune response is more effective in the protection against viral infection and open the possibility to drive it into a desired direction by choosing appropriate combinations of adjuvants.
Author: Vanessa Ronconi
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W105179019