Salivary, serological, and cellular immune response to the CoronaVac vaccine in health care workers with or without previous COVID-19.

We investigated the anti-SARS-CoV-2 post-vaccine response through serum and salivary antibodies, serum antibody neutralizing activity and cellular immune response in samples from health care workers who were immunized with two doses of an inactivated virus-based vaccine (CoronaVac) who had or did not have COVID-19 previously. IgA and IgG antibodies directed at the spike protein were analysed in samples of saliva and/or serum by ELISA and/or chemiluminescence assays; the neutralizing activity of serum antibodies against reference strain B, Gamma and Delta SARS-CoV-2 variants were evaluated using a virus neutralization test and SARS-CoV-2 reactive interferon-gamma T-cell were analysed by flow cytometry. CoronaVac was able to induce serum and salivary IgG anti-spike antibodies and IFN-γ producing T cells in most individuals who had recovered from COVID-19 and/or were vaccinated. Virus neutralizing activity was observed against the ancestral strain, with a reduced response against the variants. Vaccinated individuals who had previous COVID-19 presented higher responses than vaccinated individuals for all variables analysed. Our study provides evidence that the CoronaVac vaccine was able to induce the production of specific serum and saliva antibodies, serum virus neutralizing activity and cellular immune response, which were increased in previously COVID-19-infected individuals compared to uninfected individuals.

Immunogenicity of personalized dendritic-cell therapy in HIV-1 infected individuals under suppressive antiretroviral treatment: interim analysis from a phase II clinical trial.

BACKGROUND: We developed a personalized Monocyte-Derived Dendritic-cell Therapy (MDDCT) for HIV-infected individuals on suppressive antiretroviral treatment and evaluated HIV-specific T-cell responses. METHODS: PBMCs were obtained from 10 HIV+ individuals enrolled in trial NCT02961829. Monocytes were differentiated into DCs using IFN-α and GM-CSF. After sequencing each patient's HIV-1 Gag and determining HLA profiles, autologous Gag peptides were selected based on the predicted individual immunogenicity and used to pulse MDDCs. Three doses of the MDDCT were administered every 15 days. To assess immunogenicity, patients' cells were stimulated in vitro with autologous peptides, and intracellular IL-2, TNF, and interferon-gamma (IFN-γ) production were measured in CD4+ and CD8+ T-cells. RESULTS: The protocol of ex-vivo treatment with IFN-α and GM-CSF was able to induce maturation of MDDCs, as well as to preserve their viability for reinfusion. MDDCT administration was associated with increased expression of IL-2 in CD4+ and CD8+ T-cells at 15 and/or 30 days after the first MDDCT administration. Moreover, intracellular TNF and IFN-γ expression was significantly increased in CD4+ T-cells. The number of candidates that increased in vitro the cytokine levels in CD4+ and CD8+ T cells upon stimulation with Gag peptides from baseline to day 15 and from baseline to day 30 and day 120 after MDDCT was significant as compared to Gag unstimulated response. This was accompanied by an increasing trend in the frequency of polyfunctional T-cells over time, which was visible when considering both cells expressing two and three out of the three cytokines examined. CONCLUSIONS: MDDC had a mature profile, and this MDDCT promoted in-vitro T-cell immune responses in HIV-infected patients undergoing long-term suppressive antiretroviral treatment. Trial registration NCT02961829: (Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure, https://www.clinicaltrials.gov/ct2/show/NCT02961829 , posted November 11th, 2016).

Phenotypic and functional profile of IFN-α-differentiated dendritic cells (IFN-DCs) from HIV-infected individuals.

Dendritic cell (DC)-based immunotherapy is a promising strategy for the treatment of HIV-infected individuals. Different from the conventional protocol for DC differentiation based on the cytokine IL-4 (IL4-DCs), several studies have suggested obtaining DCs by culturing monocytes with type I IFN (IFN-α) to yield IFN-DCs, as performed in cancer therapy. To evaluate the phenotypic and functional characteristics, monocytes from HIV-infected subjects were differentiated into IFN-DCs or IL4-DCs, pulsed with chemically inactivated HIV and stimulated with pro-inflammatory cytokines. A comparative analysis between both types of monocyte-derived DCs (MoDCs) showed that immature IFN-DCs were phenotypically distinct from immature IL4-DCs at the baseline of differentiation, presenting a pre-activated profile. From the functional profile, we determined that IFN-DCs were capable of producing the cytokine IL-12 p70 and of inducing the production of IFN-γ by CD4 + T lymphocytes but not by TCD8+ lymphocytes. Our results suggest that IFN-DCs derived from HIV-infected individuals are able to recognize and present viral antigens to induce TCD4+ cellular immunity to HIV.

Characterization of monocyte-derived dendritic cells used in immunotherapy for HIV-1-infected individuals.

AIMS: A therapeutic vaccine based on monocyte-derived dendritic cells (MDDCs) has been shown to represent a promising strategy for the treatment of cancer and viral infections. Here, we characterized the MDDCs used as an immunogen in a clinical trial for an anti-HIV-1 therapeutic vaccine. PATIENTS & METHODS: Monocytes obtained from 17 HIV-infected individuals were differentiated into MDDCs and, after loading with autologous HIV, the cells were characterized concerning surface molecule expression, migratory and phagocytosis capacity, cytokine production and the induction of an effective cell-mediated immune response. RESULTS: The MDDCs were able to induce antigen-specific responses in autologous CD4+ and CD8+ T lymphocytes. CONCLUSIONS: Despite a large interindividual variability, the results suggested that MDDCs present the potential to promote immune responses in vaccinated patients.

Using Dendritic Cell-Based Immunotherapy to Treat HIV: How Can This Strategy be Improved?

Harnessing dendritic cells (DC) to treat HIV infection is considered a key strategy to improve anti-HIV treatment and promote the discovery of functional or sterilizing cures. Although this strategy represents a promising approach, the results of currently published trials suggest that opportunities to optimize its performance still exist. In addition to the genetic and clinical characteristics of patients, the efficacy of DC-based immunotherapy depends on the quality of the vaccine product, which is composed of precursor-derived DC and an antigen for pulsing. Here, we focus on some factors that can interfere with vaccine production and should thus be considered to improve DC-based immunotherapy for HIV infection.