Anders Sönnerborg

The unifying aim of VIROMARKERS is to define virus related biomarkers to improve management of chronic diseases, including biomarkers of response to antiviral treatment of persistent viral infections and virome features as indicators of disease progression in immunosuppressed people. The project has the following objectives: 1. To demonstrate a novel bioinformatics method for prediction of HIV-1 susceptibility to broadly neutralising antibodies based on the HIV-1 gp120 sequence. 2. To demonstrate novel HDV biomarkers (HDV-RNA, HBsAg isoforms and HDV genotype) to predict treatment response to the recently approved anti-HDV bulevirtide. 3. To validate serum CMV-RNA as a biomarker of CMV infection/reactivation to optimise the correct timing for preventive strategies in patients undergoing hematopoietic stem cell transplantation. 4. To validate the torque teno virus DNA as a prognostic biomarker for CMV disease in immunocompromised patients. 5. To validate total and intact cellular HIV DNA as a biomarker of HIV infection status to guide novel antiviral strategies. Validation or demonstration of several technologies required to measure the candidate biomarkers is an integral part of the project objectives. In particular, this refers to the following diagnostic tools: • dPCR as a tool for HDV quantification • NGS platform for HDV sequencing • qPCR diagnostics for CMV-RNA quantification • IPDA suitable for detection of intact HIV-DNA in any viral subtype • qPCR diagnostics for TTV-DNA Leveraging on the regulatory expertise present in the consortium, VIROMARKERS will define the regulatory pathway for each of its outcomes and will generate the experimental data necessary to move prototype methods and tools to regulatory approval. Overall, VIROMARKERS, with its public private partnership nature, will make available for healthcare providers and for researchers robust and fit-for-purpose biomarkers and linked technologies enabling their clinical use in response to important unmet clinical needs with, in the end, an important impact also for patients. VIROMARKERS is supported by the Innovative Health Initiative Joint Undertaking (IHI JU). The JU receives support from the European Union’s Horizon Europe research and innovation programme and COCIR, EFPIA, Europa Bío, MedTech Europe, and Vaccines Europe

Current HIV cure trials primarily focus on people living with HIV (PLWH) who started antiretroviral therapy (ART) during the primary infection stage, as they are known to have smaller HIV reservoirs. However, there is a substantial knowledge gap regarding the size of the HIV reservoir in majority of PLWH. Our study aims to address this gap by exploring the size of the HIV reservoir through comprehensive clinical, immunological, and virological assessments, and by developing an algorithm to predict HIV reservoir size.To achieve this, the CHART-C study will include 200 PLWH on long-term successful ART, with a substudy examining the HIV reservoir in the central nervous system of 20 participants. We will use advanced assays such as IPDA, CADseq method, and quantification of HIV-specific humoral/cellular responses. Machine learning techniques will be employed to develop an algorithm to identify individuals with the smallest HIV reservoirs.The outcome of this study will be a clinical algorithm designed to select individuals with the smallest HIV reservoirs, thereby optimizing the inclusion criteria for future HIV cure trials and enhancing the potential for therapeutic success. Additionally, we will prepare for an analytical treatment interruption  HIV cure trial using two long-acting broadly neutralizing antibodies. The CHART-C trial aims to make a significant contribution to global HIV cure strategies and position Swedish HIV research at the forefront of this critical field.

Currently, there are no vaccines against HIV (human immunodeficiency virus) and HSV (herpes simplex virus) infections. Condom, when used properly, are the most effective means of prophylaxis against viral transmission. However, there is a significant gender imbalance in condom use because women are not always in control over their use. In addition, women are at least twice as likely as men to contract sexually transmitted infections (STIs) from infected partners. Several STIs, including HIV, are underdiagnosed due to asymptomatic infections and/or lack of testing facilities. This is particularly problematic for women from African countries, who are at high risk of contracting STIs but have poor access to testing facilities. Alternatives to condoms that use established antivirals for HIV prophylaxis come with issues such as antimicrobial resistance and low adherence in practice in high-risk groups. There are also no means other than condoms for prophylaxis against HSV. Co-infection with HIV/HSV results in a vicious cycle of mutual facilitation, as individuals who are carriers of HSV have a three- to fourfold increased risk of contracting HIV. Inspired by nature, NatProLub develops a radically novel prophylactic approach to HIV and HSV prophylaxis through the use of lubricants. By targeting women, who are particularly at risk, NatProLub has a clear vision for a user-friendly, prophylactic product that can redress the gender imbalance in sexual health while offering a low risk of side effects and avoiding the risk of developing antimicrobial resistance. The members of the NatProLub consortium have very strong backgrounds in relevant but complementary scientific disciplines that will contribute to the development of prophylactic lubricants for end users and have previous successful experience in managing large scientific projects, the creation of spin-off companies, and maintaining well-developed professional networks in academia, industry, and healthcare.

The EuCARE project gathers a comprehensive multidisciplinary team of clinicians, virologists, epidemiologists, statisticians and top experts in artificial intelligence to unveil the impact of SARS-CoV-2 variants on key sectors of public health, as addressed by the call. The specific activities include: 1. The assessment of natural and artificial immunity to the different viral variants in health care workers with the aim of defining the cross-immunization patterns and the risk of vaccine escape, informing vaccination strategies for the general population

2. The analysis of the clinical course and long-term follow-up of hospitalized COVID-19 patients to derive the role of different viral variants in the outcome of the infection, including post-acute sequelae of SARS-CoV-2 infection

3. The definition of the best strategies to control the spread of different viral variants in schools, by comparing the outcome of diverse containment and prevention measures in relation to the prevalence and dynamics of the variants. To ensure a suitable representativeness of the different variants, vaccines and preventive measures, EuCARE has secured the appropriate cohorts from diverse geographic areas including European countries, Kenya, Mexico, Russia and Vietnam, and will consolidate or expand interactions with other cohorts. To deal with complex interactions among many variables, including large dimensional parameters, EuCARE harnesses the power of artificial intelligence to define the role of viral variants and inform clinical guidelines and prevention measures. In the longer-term, EuCARE is committed to maintain active cooperation beyond the duration of the project with a dedicated task in the project. The solid IT and ethics infrastructure and the harmonised research procedures will make the cohort and laboratory network rapidly available to tackle newly emerging infectious diseases, thus contributing to pandemic preparedness on a global scale.