PhD student:

Rebecca Heß, M.Sc.

Institute of Molecular and Medical Virology,
Ruhr University Bochum

rebecca.hess@rub.de

Phone: +49 234 32 27834

Differential stimulation of innate immune responses by viral

surface proteins modulating the antiviral antibody response

The adaptive immune response to infections with different viruses differs in strength and quality. Determinants of these differences in the adaptive immune response are difficult to pinpoint, since many factors, including tropism, replication kinetics, stimulation of innate immune responses, antigenic structure, and immunomodulatory viral proteins may shape the type of adaptive immune response raised. We previously observed that the ratio of IgG1 to IgG2a antibodies against different viral surface proteins induced by the same intramuscular DNA electroporation differs substantially. Thus, the nature of the viral surface protein seems to determine the type of antibody response induced. Differential stimulation of innate immune responses by the viral surface proteins may explain this observation. Therefore, the project aims to explore the role of molecular mechanisms of the innate immune system as determinants of the differences in the antibody responses. A better understanding of the type of B cell responses induced by vaccination will be important to raise antibodies with desired Fc-mediated effector functions.

Publications

Nabi G, Temchura V, Grossmann C, Kuate S, Tenbusch M, Uberla K. T cell independent secondary antibody responses to the envelope protein of simian immunodeficiency virus. Retrovirology 2012;9:42.

Tenbusch M, Ignatius R, Nchinda G, Trumpfheller C, Salazar AM, Topfer K, Sauermann U, Wagner R, Hannaman D, Tenner-Racz K, Racz P, Stahl-Hennig C, Uberla K. Immunogenicity of DNA vaccines encoding simian immunodeficiency virus antigen targeted to dendritic cells in rhesus macaques. PLoS One 2012a;7:e39038.

Tenbusch M, Ignatius R, Temchura V, Nabi G, Tippler B, Stewart-Jones G, Salazar AM, Sauermann U, Stahl-Hennig C, Uberla K. Risk of immunodeficiency virus infection may increase with vaccine-induced immune response. J Virol 2012b;86:10533-9.

Tenbusch M, Grunwald T, Niezold T, Storcksdieck Genannt Bonsmann M, Hannaman D, Norley S, Uberla K. Codon-optimization of the hemagglutinin gene from the novel swine origin H1N1 influenza virus has differential effects on CD4(+) T-cell responses and immune effector mechanisms following DNA electroporation in mice. Vaccine 2010;28:3273-7.

Kohlmann R, Schwannecke S, Tippler B, Ternette N, Temchura VV, Tenbusch M, Uberla K, Grunwald T. Protective efficacy and immunogenicity of an adenoviral vector vaccine encoding the codon-optimized F protein of respiratory syncytial virus. J Virol 2009;83:12601-10.

Stahl-Hennig C, Eisenblatter M, Jasny E, Rzehak T, Tenner-Racz K, Trumpfheller C, Salazar AM, Uberla K, Nieto K, Kleinschmidt J, Schulte R, Gissmann L, Muller M, Sacher A, Racz P, Steinman RM, Uguccioni M, Ignatius R. Synthetic double-stranded RNAs are adjuvants for the induction of T helper 1 and humoral immune responses to human papillomavirus in rhesus macaques. PLoS Pathog 2009;5:e1000373.

Nchinda G, Kuroiwa J, Oks M, Trumpfheller C, Park CG, Huang Y, Hannaman D, Schlesinger SJ, Mizenina O, Nussenzweig MC, Uberla K, Steinman RM. The efficacy of DNA vaccination is enhanced in mice by targeting the encoded protein to dendritic cells. J Clin Invest 2008;118:1427-36.

Stahl-Hennig C, Kuate S, Franz M, Suh YS, Stoiber H, Sauermann U, Tenner-Racz K, Norley S, Park KS, Sung YC, Steinman R, Racz P, Uberla K. Atraumatic oral spray immunization with replication-deficient viral vector vaccines. J Virol 2007;81:13180-90.

Ternette N, Tippler B, Uberla K, Grunwald T. Immunogenicity and efficacy of codon optimized DNA vaccines encoding the F-protein of respiratory syncytial virus. Vaccine 2007;25:7271-9.