rapid-vivo-assessment-adjuvant-s-cytotoxic-t-lymphocytes-generation

Rapid <em>In Vivo</em> Assessment of Adjuvant's Cytotoxic T Lymphocytes Generation Capabilities for Vaccine Development

The assessment of modern sub-unit vaccines reveals that the generation of neutralizing antibodies is important but not sufficient for adjuvant selection. ...

Helmholtz Centre for Infection Research

EUMORPHIA (European Union Mouse Research for Public Health and Industrial Application) is a research program involved in developing new approaches in phenotyping, mutagenesis, and informatics to improve characterization of mouse models for understanding human physiology and disease. Secondary screen experiments include the development of assays to identify mice with altered susceptibility or resistance to infections. In this context we developed a new model and established a standard operating procedure for the experimental infection of mice with Yersinia (Y.) enterocolitica. In contrast with previous studies that dealt with high-pathogenic Y. enterocolitica, we used the low-pathogenic Y. enterocolitica strain E40 to analyze differences in the immune response of four strains of inbred mice (BALB/c, C3H/HeN, 129P2, C57BL/6) after oral infection. The determination of colony-forming units in Peyer's patches and histologic analysis supported the observations that BALB/c are less able to ameliorate the infection within 21 days. The immune defense of C57BL/6 mice against Yersinia was the most effective resulting in a nearly complete elimination of bacteria after 21 days. C3H/HeN and 129P2 were intermediate. Analysis of serum immunoglobulins (Ig) by Luminex showed a significant increase of IgG2b levels 21 days after infection in all four inbred strains. The other immunoglobulins remained nearly constant. Our infection model discriminates between the efficiency of an infection at an early time point (3 days) and immunity at a later time point (21 days). It is furthermore an appropriate model to characterize genetic differences in resistance and immunity of inbred and mutant mouse lines.

Susceptibility of four inbred mouse strains to a low-pathogenic isolate of Yersinia enterocolitica.

Vaccines represent the most efficient tool for preventing diseases caused by infectious pathogens. During the last century significant progress has been made in vaccine development, resulting in the eradication or control of several diseases. However, the emergence of new pathogens and the inadequate protection conferred by some existing vaccines render necessary new vaccination strategies. Newly arising immunization approaches, such as subunit vaccines and mucosal administration, make the use of novel adjuvants essential. However, only a limited number of adjuvants are available on the market. The present review is focused on vaccine adjuvants approved for human vaccines and promising candidates which are currently under development. In this regard, emerging immune stimulators and combinations are discussed, together with their strengths, limitations and regulatory framework. 

Vaccine adjuvants: key tools for innovative vaccine design.

The young twenty-first century has already brought several medical advances, such as a functional artificial human liver created from stem cells, improved antiviral (e.g., against HIV) and cancer (e.g., against breast cancer) therapies, interventions controlling cardiovascular diseases, and development of new and optimized vaccines (e.g., HPV vaccine). However, despite this substantial progress and the achievements of the last century, humans still suffer considerably from diseases, especially from infectious diseases. Thus, almost one-fourth of all deaths worldwide are caused directly or indirectly by infectious agents. Although vaccination has led to the control of many diseases, including smallpox, diphtheria, and tetanus, emerging diseases are still not completely contained. Furthermore, pathogens such as Bordetella pertussis undergo alterations making adaptation of the respective vaccine necessary. Moreover, insufficient implementation of vaccination campaigns leads to re-emergence of diseases which were believed to be already under control (e.g., poliomyelitis). Therefore, novel vaccination strategies need to be developed in order to meet the current challenges including lack of compliance, safety issues, and logistic constraints. In this context, mucosal and transdermal approaches constitute promising noninvasive vaccination strategies able to match these demands.

New Horizons in the Development of Novel Needle-Free Immunization Strategies to Increase Vaccination Efficacy.

Participation in epidemiological studies has strongly declined in recent years. We examined the reasons for (non)participation in population-based health studies among participants and nonparticipants of a prospective study on influenza vaccination among the elderly.

Motivations for (non)participation in population-based health studies among the elderly - comparison of participants and nonparticipants of a prospective study on influenza vaccination.

Elderly individuals have the highest burden of disease from influenza infection but also the lowest immune response to influenza vaccination. A better understanding of the host response to influenza vaccination in the elderly is therefore urgently needed. We conducted a biphasic prospective, population-based study from Dec. 2014 to May 2015 (pilot study) and Sept. 2015 to May 2016 (main study). Individuals 65-80 y of age were randomly selected from the residents' registration office in Hannover, Germany, for the pilot (n = 34) and main study (n = 200). The pilot study tested recruitment for study arms featuring 2, 4, or 5 visits/blood draws. The 5-visit (day 0, 1/3, 7, 21, 70 with respect to vaccination) study arm was selected for the main study. Both studies featured vaccination with Fluad™ (Novartis, Italy), a detailed medical history, a physical exam, recording of adverse events, completion of a questionnaire on common infections and an end-of-study questionnaire, and blood samples. Response rates in the pilot and main studies were 3.7% and 4.0%, respectively. Willingness to participate did not differ among the study arms (Fisher's exact test, p = 0.44). In both studies, there were no losses to follow-up. Compliance with study visits, blood sampling and completion of the questionnaires was very high (100%, >97%, 100%, respectively), as were participants' acceptance of and satisfaction with both phases of the study. The low response rates indicate the need for optimized recruitment strategies if the study population is to be representative of the general population. Nonetheless, the complex prospective study design proved to be highly feasible.

Establishment of a cohort for deep phenotyping of the immune response to influenza vaccination among elderly individuals recruited from the general population.

Article	Year
Susceptibility of four inbred mouse strains to a low-pathogenic isolate of Yersinia enterocolitica. Mammalian genome : official journal of the International Mammalian Genome Society\| PubMed ID: 18392655	2008
Vaccine adjuvants: key tools for innovative vaccine design. Current topics in medicinal chemistry\| PubMed ID: 24066891	2013
New Horizons in the Development of Novel Needle-Free Immunization Strategies to Increase Vaccination Efficacy. Current topics in microbiology and immunology\| PubMed ID: 27370343	2016
Motivations for (non)participation in population-based health studies among the elderly - comparison of participants and nonparticipants of a prospective study on influenza vaccination. BMC medical research methodology\| PubMed ID: 28148221	2017
Establishment of a cohort for deep phenotyping of the immune response to influenza vaccination among elderly individuals recruited from the general population. Human vaccines & immunotherapeutics\| PubMed ID: 28394705	2017

Blair Prochnow

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