Biology subjects

Gea-Mallorqui, E.

Publications and source records attributed to Gea-Mallorqui, E..

4 recordsLinked to original sources

bioRxiv2023

The Preprint Club - A cross-institutional, community-based approach to peer reviewing

The academic community has been increasingly using preprints to disseminate their latest research findings quickly and openly. This early and open access of non-peer reviewed research warrants new means from the scientific community to efficiently assess and provide feedback to preprints. Yet, most peer review of scientific studies performed today are still managed by journals, each having their own peer review policy and transparency. However, approaches to uncouple the peer review process from journal publication are emerging. Additionally, formal education of early career researchers (ECRs) in peer reviewing is rarely available, hampering the quality of peer review feedback. Here, we introduce the Preprint Club, a cross-institutional, community-based approach to peer reviewing, founded by ECRs from the University of Oxford, Karolinska Institutet and Icahn School of Medicine at Mount Sinai. Over the past two years and using the collaborative setting of the Preprint Club, we have been discussing, assessing, and providing feedback on recent preprints in the field of immunology. In this article, we provide a blueprint of the Preprint Club basic structure, demonstrate its effectiveness, and detail the lessons we learned on its impact on peer review training and preprint authors perception.

scientific communication and education↗

bioRxiv2022

Attenuated humoral responses in HIV infection after SARS-CoV-2 vaccination are linked to global B cell defects and cellular immune profiles

People living with HIV (PLWH) on suppressive antiretroviral therapy (ART) can have residual immune dysfunction and often display poorer responses to vaccination. We assessed in a cohort of PLWH (n=110) and HIV negative controls (n=64) the humoral and spike-specific B-cell responses following 1, 2 or 3 SARS-CoV-2 vaccine doses. PLWH had significantly lower neutralizing antibody (nAb) titers than HIV-negative controls at all studied timepoints. Moreover, their neutralization breadth was reduced with fewer individuals developing a neutralizing response against the Omicron variant (BA.1) relative to controls. We also observed a delayed development of neutralization in PLWH that was underpinned by a reduced frequency of spike-specific memory B cells (MBCs) and pronounced B cell dysfunction. Improved neutralization breadth was seen after the third vaccine dose in PLWH but lower nAb responses persisted and were associated with global, but not spike-specific, MBC dysfunction. In contrast to the inferior antibody responses, SARS-CoV-2 vaccination induced robust T cell responses that cross-recognized variants in PLWH. Strikingly, a subset of PLWH with low or absent neutralization had detectable functional T cell responses. These individuals had reduced numbers of circulating T follicular helper cells and an enriched population of CXCR3+CD127+CD8+ T cells after two doses of SARS-CoV-2 vaccination, which may compensate for sub-optimal serological responses in the event of infection. Therefore, normalisation of B cell homeostasis could improve serological responses to vaccines in PLWH and evaluating T cell immunity could provide a more comprehensive immune status profile in these individuals and others with B cell imbalances.

immunology↗

bioRxiv2021

Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV

There is an urgent need to understand the nature of immune responses generated against SARS-CoV-2, to better inform risk-mitigation strategies for people living with HIV (PLWH). Although not all PLWH are considered immunosuppressed, residual cellular immune deficiency and ongoing inflammation could influence COVID-19 disease severity, the evolution and durability of protective memory responses. Here, we performed an integrated analysis, characterizing the nature, breadth and magnitude of SARS-CoV-2-specific immune responses in PLWH, controlled on ART, and HIV negative subjects. Both groups were in the convalescent phase of predominately mild COVID-19 disease. The majority of PLWH mounted SARS-CoV-2 Spike- and Nucleoprotein-specific antibodies with neutralizing activity and SARS-CoV-2-specific T cell responses, as measured by ELISpot, at levels comparable to HIV negative subjects. T cell responses against Spike, Membrane and Nucleocapsid were the most prominent, with SARS-CoV-2-specific CD4 T cells outnumbering CD8 T cells. Notably, the overall magnitude of SARS-CoV-2-specific T cell responses related to the size of the naive CD4 T cell pool and the CD4:CD8 ratio in PLWH, in whom disparate antibody and T cell responses were observed. Both humoral and cellular responses to SARS-CoV-2 were detected at 5-7 months post-infection, providing evidence of medium-term durability of responses irrespective of HIV serostatus. Incomplete immune reconstitution on ART and a low CD4:CD8 ratio could, however, hamper the development of immunity to SARS-CoV-2 and serve as a useful tool for risk stratification of PLWH. These findings have implications for the individual management and potential effectiveness of vaccination against SARS-CoV-2 in PLWH. One Sentence SummaryAdaptive immune responses to SARS-CoV-2 in the setting of HIV infection

immunology↗

bioRxiv2019

Constitutive Siglec-1 expression by human dendritic cell precursors enables HIV-1 replication and transmission

Human dendritic cell (DC) lineage has been recently unraveled by high dimensional mapping revealing the existence of a discrete new population of blood circulating DC precursor (pre-DC also referred to as AS DC). Among all blood DC subsets, only pre-DC highly express Siglec-1, a lectin-like receptor able to bind HIV-1. We show that pre-DC are uniquely equipped among blood DC populations to promote HIV-1 replication and dissemination. Pre-DC stands out as the most susceptible DC population to infection by both HIV-1 CXCR4- and CCR5-tropic viral particles in a Siglec-1-dependent manner. HIV-1-infected pre-DC produce new viral progeny and transmit the virus to CD4+ T cells. Upon TLR activation, pre-DC become resistant to HIV-1 fusion and thus to infection and switch to a replication-independent mechanism of virus transfer to activated primary T lymphocytes mediated by Siglec-1. Thus, beside their role in DC ontogeny, blood pre-DC possess stage-specific properties that HIV-1 may exploit for viral spreading and modulation of the immune response.

immunology↗