Julia G Prado

IrsiCaixa Research Institute and Germans Trias i Pujol Research Institute

The co-expression of inhibitory receptors (IRs) is a hallmark of CD8+ T-cell exhaustion (Tex) in people living with HIV-1 (PLWH). Understanding alterations of IRs expression in PLWH on long-term antiretroviral treatment (ART) remains elusive but is critical to overcoming CD8+ Tex and designing novel HIV-1 cure immunotherapies. To address this, we c...

Current HIV-1 therapeutic vaccines do not generate T-cell immune responses in people with HIV-1 (PWH) able to eradicate the virus or to broadly control viral replication. The expression of inhibitory receptors (IRs) may limit vaccine efficacy by reducing specific effector functions in vaccine-induced T-cells. Recently, the clinical use of antibodie...

Introduction There is a growing interest in the effect of Long-COVID (LC) on cognition, and neuroimaging allows us to gain insight into the structural and functional changes underlying cognitive impairment in LC. We used multimodal neuroimaging data in combination with neuropsychological evaluations to study cognitive complaints in a cohort of LC p...

Humanized immunodeficient mice serve as critical models for investigating the functional interplay between transplanted human cells and a pre-reconstituted human immune system. These models facilitate the study of molecular and cellular pathogenic mechanisms and enable the evaluation of the efficacy and toxicity of immunotherapies, thereby accelera...

Background As the vaccination campaign against COVID-19 progresses, it becomes crucial to comprehend the lasting effects of vaccination on safeguarding against new infections or reinfections. Objective This study aimed to assess the risk of new SARS-CoV-2 infections based on the number of vaccine doses, prior infections, and other clinical charact...

(1) Background: The global coronavirus disease 2019 vaccination adapts to protect populations from emerging variants. This communication presents interim findings from the new Omicron XBB.1.16-adapted PHH-1V81 protein-based vaccine compared to an XBB.1.5-adapted mRNA vaccine against various acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stra...

Background The neurological symptoms of Long COVID (LC) and the impact of neuropsychological manifestations on people’s daily lives have been extensively described. Although a large body of literature describes symptoms, validating this with objective measures is important. This study aims to identify and describe the effects of Long COVID on cogni...

In this phase III, open label, single arm, multicenter clinical study, we report safety, tolerability and immunogenicity of PHH-1V as a booster dose in subjects primary vaccinated against COVID-19 with the BNT162b2, mRNA-1273, ChAdOx1-S, or Ad26.COV2.S vaccines, with or without previous COVID-19 infection. A total of 2661 subjects were included in...

Background Global COVID-19 vaccination adapts to protect populations from emerging variants. This communication presents interim findings from the new Omicron XBB adapted PHH-1V81 vaccine compared to a XBB adapted mRNA vaccine against XBB and JN.1 SARS-CoV-2 strains. Methods In a Phase IIb/III pivotal trial, adults previously vaccinated with a pri...

Background Phase IIb HIPRA-HH-2 study results showed that PHH-1V as first booster dose elicited a strong and sustained neutralising antibody response against various SARS-CoV-2 variants. Here, we report the safety and immunogenicity of a fourth booster dose of PHH-1V against the most prevalent Omicron SARS-CoV-2 variants in Spain. Methods The HIPR...

Natural Killer (NK) cells are promising tools for the development of immunotherapies targeting persistently infected CD4+ T cells to potentially achieve remission in people with HIV-1 (PWH). However, the chronicity of HIV-1 infection limits the functional properties of NK cells, and additional approaches are needed to potentiate their cytotoxic act...

Background and purpose: There is a paucity of data on long-term neuroimaging findings from individuals who have developed the post-coronavirus 2019 (COVID-19) condition. Only 2 studies have investigated the correlations between cognitive assessment results and structural MR imaging in this population. This study aimed to elucidate the long-term cog...

The HIPRA-HH-2 was a multicentre, randomized, active-controlled, double-blind, non-inferiority phase IIb clinical trial to compare the immunogenicity and safety of a heterologous booster with PHH-1V adjuvanted recombinant vaccine versus a homologous booster with mRNA vaccine. Interim results showed a strong humoral and cellular immune response agai...

Background: A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versu...

Current COVID-19 vaccines have been associated with a decline in infection rates, prevention of severe disease and a decrease in mortality rates. However, SARS-CoV-2 variants are continuously evolving, and development of new accessible COVID-19 vaccines is essential to mitigate the pandemic. Here, we present data on preclinical studies in mice of a...

The implementation and access to combined antiretroviral treatment (cART) have dramatically improved the quality of life of people living with HIV (PLWH). However, some comorbidities, such as neurological disorders associated with HIV infection still represent a serious clinical challenge. Soluble factors in plasma that are associated with control...

HIV non-progression despite persistent viraemia is rare among antiretroviral therapy (ART)-naïve adults, but relatively common among ART-naïve children. Previous studies indicate that ART-naïve paediatric slow-progressors (PSPs) adopt immune evasion strategies similar to those described in the SIV natural hosts. However, the mechanisms underlying t...

Background Long-Term Non-Progressors (LTNPs) are untreated Human Immunodeficiency virus type 1 (HIV-1) infected individuals able to control disease progression for prolonged periods. However, the LTNPs status is temporary, as viral load increases followed by decreases in CD4 + T-cell counts. Control of HIV-1 infection in LTNPs viremic controllers,...

Mass vaccination campaigns reduced COVID-19 incidence and severity. Here, we evaluated the immune responses developed in SARS-CoV-2-uninfected patients with predominantly antibody-deficiencies (PAD) after three mRNA-1273 vaccine doses. PAD patients were classified based on their immunodeficiency: unclassified primary antibody-deficiency (unPAD, n=9...

We describe a case of a patient who experienced recurrent COVID-19 pneumonia over a period of 123 days. Neither remdesivir nor convalescent plasma were temporally associated with viral clearance or increased plasma neutralization capacity. Antibody levels remained low until day 151 and cellular immunity increased overtime with no viral evolution.

From March to September 2020, researchers working at a biomedical scientific campus in Spain faced two lockdowns and various mobility restrictions that affected their social and professional lifestyles. The working group “Women in Science,” which acts as an independent observatory of scientific gender inequalities on campus launched an online surve...

Background Understanding the immune response to the SARS-CoV-2 virus is critical for efficient monitoring and control strategies. The ProHEpic-19 cohort provides a fine-grained description of the kinetics of antibodies after SARS-CoV-2 infection with an exceptional resolution over 17 months. Methods We established a cohort of 769 healthcare worker...

The expression of inhibitory receptors (IRs) is a hallmark of CD8+ T-cell exhaustion (Tex) in people living with HIV-1 (PLWH). Understanding the dynamics of IRs expression in PLWH on long-term antiretroviral treatment (ART) is critical to overcoming CD8+ Tex and designing broadly applicable HIV-1 immunotherapies for cure. To address this, we combin...

Background A SARS-CoV-2 protein-based heterodimer vaccine, PHH-1V, has been shown to be safe and well-tolerated in healthy young adults in a first-in-human, Phase I/IIa study dose-escalation trial. Here, we report the interim results of the Phase IIb HH-2, where the immunogenicity and safety of a heterologous booster with PHH-1V is assessed versus...

The diagnosis of the post-COVID condition is usually achieved by excluding other diseases; however, cognitive changes are often found in the post-COVID disorder. Therefore, monitoring and treating the recovery from the post-COVID condition is necessary to establish biomarkers to guide the diagnosis of symptoms, including cognitive impairment. Our s...

The role of T cells in the control of SARS-CoV-2 infection has been underestimated in favor of neutralizing antibodies. However, cellular immunity is essential for long-term viral control and protection from disease severity. To understand T-cell immunity in the absence of antibody generation we focused on a group of SARS-CoV-2 Non-Seroconvertors (...

Purpose Mass vaccination campaigns have reduced the incidence and severity of COVID-19. However, there is limited information about how patients with predominantly antibody-deficiencies (PAD) respond to COVID-19 vaccination. Here, we evaluated humoral and cellular responses developed in SARS-CoV-2-naïve PAD individuals after three mRNA-1273 vaccine...

Background Understanding the immune response to the SARS-CoV-2 virus is critical for efficient monitoring and defence strategies. The ProHEpic-19 cohort provides a fine-grained description of the kinetics of antibodies after SARS-CoV-2 infection with an exceptional resolution over 17 months.Methods We established a cohort of 769 health professional...

HIV-1 viremic nonprogressors (VNPs) represent a very rare HIV-1 extreme phenotype. VNPs are characterized by persistent high plasma viremia and maintenance of CD4+ T cell counts in the absence of treatment. However, the causes of nonpathogenic HIV-1 infection in VNPs remain elusive. Here, we identified for the first time two VNPs who experienced th...

The current COVID-19 vaccines have been associated with a decline in infection rates, prevention of severe disease and decrease in mortality rates. However, new variants of concern (VoCs) are continuously evolving, making the development of new accessible COVID-19 vaccines essential in order to mitigate the pandemic. Here we present data on preclin...

Background: Understanding humoral responses and seroprevalence in SARS-CoV-2 infection is essential for guiding vaccination strategies in both infected and uninfected individuals. Methods: We determine the kinetics of IgM against the nucleocapsid (N) and IgG against the spike (S) and N proteins of SARS-CoV-2 in a cohort of 860 health professionals...

Background SARS-CoV-2 reinfections have been reported; however, most cases are milder than the primary infection. We report the first case of a life-threatening critical presentation of a SARS-CoV-2 reinfection. Case presentation A 62-year male from Palamós (Spain) suffered a first mild COVID-19 episode in March 2020, confirmed by 2 independent SA...

Current efforts aimed at finding a definitive cure for HIV-1 infection are hampered mainly by the persistence of a viral reservoir in latently infected cells. While complete viral eradication from the body remains elusive, finding a functional cure to enable control of viremia without the need for continuous treatment is a key goal.

The role of T cells in the control of SARS-CoV-2 infection has been underestimated in favor of neutralizing antibodies. However, cellular immunity is essential for long-term viral control and protection from disease severity. To understand T-cell immunity in the absence of antibody generation we focused on a group of SARS-CoV-2 Non-Seroconvertors (...

HIV represents a persistent infection which negatively alters the immune system. New tools to reinvigorate different immune cell populations to impact HIV are needed. Herein, a novel nanotool for the specific enhancement of the natural killer (NK) immune response towards HIV-infected T-cells has been developed. Bispecific Au nanoparticles (BiAb-AuN...

The Life Science Community of Practice LifeSciCoP is part of ACT (act on gender eu an Horizon 2020 project that seeks to advance gender equality at universities, research centres and research funding organisations The ACT project set up and supports an international network of Communities of Practice ( as agents to develop gender equality actions a...

Synthetic antigens based on consensus sequences that represent circulating viral isolates are sensitive, time saving and cost-effective tools for in vitro immune monitoring and to guide immunogen design. When based on a representative sequence database, such consensus sequences can effectively be used to test immune responses in exposed and infecte...

Introduction: Treatment with anti PD-1/PD-L1 antibodies has demonstrated clinical activity in different types of solid tumors, but only 20 to 30% of patients (pts) respond to these immune checkpoint inhibitors (ICIs). Therefore, predictive biomarkers of response that can assist in pt selection are urgently needed. Single biomarker expression, like...

Background: Virological failure (VF) to boosted PIs with a high genetic barrier is not usually linked to the development of resistance-associated mutations in the protease gene. Methods: From a cohort of 520 HIV-infected subjects treated with lopinavir/ritonavir or darunavir/ritonavir monotherapy, we retrospectively identified nine patients with VF...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Female children and adults typically generate more efficacious immune responses to vaccines and infections than age-matched males, but also suffer greater immunopathology and auto-immune disease. We here describe, in a cohort of > 170 in utero HIV-infected infants from KwaZulu-Natal, South Africa, fetal immune sex differences resulting in a 1.5-2-f...

Importance Therapies targeting the programmed cell death 1 (PD-1) receptor or its ligand (PD-L1), such as the humanized monoclonal antibody durvalumab, have shown durable clinical responses in several tumor types. However, concerns about the safety and feasibility of PD-1/PD-L1 blockade in HIV-1–infected individuals have led to the exclusion of the...

To attain the control or elimination of HIV-1 infection it is critical to delineate immune interventions capable of boosting or reinvigorating HIV-1-specific CD8+ T-cell responses. Immune interventions, including therapeutic vaccines or immune checkpoint inhibitors (ICIs), have been postulated to achieve this goal. However, the potency of combining...

Background: Pembrolizumab is an immune checkpoint inhibitor against programmed cell death protein-1 (PD-1) approved for therapy in metastatic melanoma. PD-1 expression is associated with a diminished functionality in HIV-1 specific-CD8+ T cells. It is thought that PD-1 blockade could contribute to reinvigorate antiviral immunity and reduce the HIV...

HIV viral reservoirs are established very early during infection. Resident memory T cells (TRM) are present in tissues such as the lower female genital tract, but the contribution of this subset of cells to the pathogenesis and persistence of HIV remains unclear. Here, we show that cervical CD4+TRM display a unique repertoire of clusters of differe...

2501 Background: Durvalumab (MEDI4736), a programmed cell death-ligand 1 (PD-L1) blocking antibody, is currently approved for treatment of several cancer types. As HIV-1-infected (HIV+) patients have been excluded from cancer clinical trials, there are no data on the safety of durvalumab in this population. Methods: DURVAST (NCT03094286) is a multi...

Relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) has a dismal outcome, and no effective targeted immunotherapies for T-ALL exist. The extension of chimeric antigen receptor (CAR) T cells (CARTs) to T-ALL remains challenging because the shared expression of target antigens between CARTs and T-ALL blasts leads to CART fratricide. CD1a...

The so-called shock and kill therapies aim to combine HIV-1 reactivation by latency-reversing agents (LRA) with immune clearance to purge the HIV-1 reservoir. The clinical use of LRA has demonstrated detectable perturbations in the HIV-1 reservoir without measurable reductions to date. Consequently, fundamental questions concerning the limitations...

Antiviral restriction factors are host cellular proteins that constitute a first line of defense blocking viral replication and propagation. In addition to interfering at critical steps of the viral replication cycle, some restriction factors also act as innate sensors triggering innate responses against infections. Accumulating evidence suggests a...

CD32 has been shown to be preferentially expressed in latently HIV-1-infected cells in an in vitro model of quiescent CD4 T cells. Here we show that stimulation of CD4+ T cells with IL-2, IL-7, PHA, and anti-CD3/CD28 antibodies induces T-cell proliferation, co-expression of CD32 and the activation of the markers HLA-DR and CD69. HIV-1 infection inc...

Viremic nonprogressors (VNPs) constitute a very scarce group of untreated human immunodeficiency virus type 1 (HIV-1)-infected individuals who maintain stable CD4⁺ T cell counts despite high levels of HIV-1 replication. The specific factors associated with this atypical control of the HIV infection have been poorly described. Since specific T cell...

HIV-1 elite controllers (EC) maintain undetectable viral loads (VL) in the absence of antiretroviral treatment. However, these subjects have heterogeneous clinical outcomes, including a proportion that loses HIV-1 control over time. In this work, we compared, in a longitudinal design, transient EC, analyzed before and after the loss of virological...

The well-characterized association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05- restricted CD8⁺ T-cell responses toward the conserved Gag KK10 (residues 263 to 272) and polymerase (Pol) KY9 (residues 901 to 909) epitopes. We studied the impact of the 3 amino acid differences betwe...

Despite the major role of Gag in establishing resistance of HIV-1 to protease inhibitors (PIs), very limited data are available on the total contribution of Gag residues to resistance to PIs. To identify in detail Gag residues and structural interfaces associated with the development of HIV-1 resistance to PIs, we traced viral evolution under the p...

Importance: New therapeutics to tackle HIV-1 infection should aim to combine rapid innate viral sensing and cellular immune recognition. Such strategies could prevent seeding of the viral reservoir and the immune damage that occurs during acute infection. The non-human TRIM5 variants, rhesus TRIM5α (RhT5) and TRIM-cyclophilin A (TCyp), are attract...