Thomas Mertens

Bio: Thomas Mertens is an academic researcher from University of Ulm. The author has contributed to research in topics: Human cytomegalovirus & Cytotoxic T cell. The author has an hindex of 39, co-authored 125 publications receiving 4110 citations.

Human cytomegalovirus-induced NKG2C(hi) CD57(hi) natural killer cells are effectors dependent on humoral antiviral immunity.

Abstract: Recent studies indicate that expansion of NKG2C-positive natural killer (NK) cells is associated with human cytomegalovirus (HCMV); however, their activity in response to HCMV-infected cells remains unclear. We show that NKG2Chi CD57hi NK cells gated on CD3neg CD56dim cells can be phenotypically identified as HCMV-induced NK cells that can be activated by HCMV-infected cells. Using HCMV-infected autologous macrophages as targets, we were able to show that these NKG2Chi CD57hi NK cells are highly responsive to HCMV-infected macrophages only in the presence of HCMV-specific antibodies, whereas they are functionally poor effectors of natural cytotoxicity. We further demonstrate that NKG2Chi CD57hi NK cells are intrinsically responsive to signaling through CD16 cross-linking. Our findings show that the activity of pathogen-induced innate immune cells can be enhanced by adaptive humoral immunity. Understanding the activity of NKG2Chi CD57hi NK cells against HCMV-infected cells will be of relevance for the further development of adoptive immunotherapy.

Antibody and cytotoxic T-cell responses to soluble hepatitis B virus (HBV) S antigen in mice: implication for the pathogenesis of HBV-induced hepatitis.

Abstract: Immune responses to components of hepatitis B virus (HBV) are assumed to play an essential role not only in the elimination of the virus but also in the pathogenesis of HBV-induced hepatitis. Protective humoral immunity to HBV is mediated by immune responses to HBV surface antigen (HBsAg). It is important to know which HBsAg preparations induce which type of cellular and humoral immune responses under which immunization conditions. We studied in BALB/c mice the humoral (antibody) response and the class I-restricted cytotoxic T-lymphocyte (CTL) response to different preparations of HBsAg particles: recombinant, small protein particles; plasma-derived, mixed particles formed by large, medium, and small surface proteins; and different preparations of recombinant, mixed particles formed by large and small surface proteins. Specific antibody levels appeared in the sera of immunized mice 2 to 3 weeks after immunization and were correlated with the antigen dose used for priming. HBsAg-specific antibody levels were enhanced by boost injections or by adsorbing the antigen to aluminum hydroxide. Injected in particulate form without adjuvants in the dose range of 0.1 to 10 micrograms per mouse, all HBsAg preparations tested efficiently primed specific CD8+ CTL of defined restriction and epitope specificity. Specific CTL reactivity was detectable from 5 days to more than 4 months postimmunization. In the dose range tested, it was independent of the antigen dose used for immunization and not enhanced by repeated boost injections. CTL were not elicited by HBsAg adsorbed to aluminum hydroxide. We have thus defined conditions under which HBsAg induced preferentially either a cellular immune response or a humoral immune response. These findings may be relevant for the interpretation of HBV-associated immunopathologic phenomena.

Active cytomegalovirus infection in patients with septic shock.

Abstract: Cytomegalovirus (CMV) is a pathogen of emerging importance for patients with septic shock. In this prospective study, 25 immunocompetent CMV-seropositive patients with septic shock and an intensive care unit stay of >7 days were monitored by using quantitative pp65-antigenemia assay, shell vial culture, and virus isolation. Within 2 weeks, active CMV infection with low-level pp65-antigenemia (median 3 positive/5×105 leukocytes) developed in 8 (32%) patients. Infection was controlled within a few weeks (median 26 days) without use of antiviral therapy. Duration of intensive care and mechanical ventilation were significantly prolonged in patients with active CMV infection. CMV reactivation was associated with concomitant herpes simplex virus reactivation (p = 0.004). The association between active CMV infection and increased illness could open new therapeutic options for patients with septic shock. Future interventional studies are required.

The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation

Abstract: Cytomegalovirus (CMV) remains one of the most common infections after solid organ transplantation, resulting in significant morbidity, graft loss, and occasional mortality. Management of CMV varies considerably among transplant centers. A panel of experts on CMV and solid organ transplant was convened by The Infectious Diseases Section of The Transplantation Society to develop evidence and expert opinion-based consensus guidelines on CMV management including diagnostics, immunology, prevention, treatment, drug resistance, and pediatric issues.

Antiherpesvirus drugs: a promising spectrum of new drugs and drug targets

Abstract: In the absence of effective vaccines to control herpesvirus infections, nucleosidic antiviral drugs have been the mainstay of clinical treatment since their development in the late 1970s. However, given the drawbacks of these drugs, including the increasing emergence of drug-resistant clinical isolates, new strategies for treating herpesvirus infections are warranted. A range of promising new drugs with novel molecular targets has been developed, but will they cure latent infections?

Vaccine adjuvants: current state and future trends.

Abstract: The problem with pure recombinant or synthetic antigens used in modern day vaccines is that they are generally far less immunogenic than older style live or killed whole organism vaccines. This has created a major need for improved and more powerful adjuvants for use in these vaccines. With few exceptions, alum remains the sole adjuvant approved for human use in the majority of countries worldwide. Although alum is able to induce a good antibody (Th2) response, it has little capacity to stimulate cellular (Th1) immune responses which are so important for protection against many pathogens. In addition, alum has the potential to cause severe local and systemic side-effects including sterile abscesses, eosinophilia and myofascitis, although fortunately most of the more serious side-effects are relatively rare. There is also community concern regarding the possible role of aluminium in neurodegenerative diseases such as Alzheimer's disease. Consequently, there is a major unmet need for safer and more effective adjuvants suitable for human use. In particular, there is demand for safe and non-toxic adjuvants able to stimulate cellular (Th1) immunity. Other needs in light of new vaccine technologies are adjuvants suitable for use with mucosally-delivered vaccines, DNA vaccines, cancer and autoimmunity vaccines. Each of these areas are highly specialized with their own unique needs in respect of suitable adjuvant technology. This paper reviews the state of the art in the adjuvant field, explores future directions of adjuvant development and finally examines some of the impediments and barriers to development and registration of new human adjuvants.