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•HAV booster vaccination elicited an adequate humoral memory response in most individuals.•HAV-specific memory T-cells response was observed independently of anti-HAV antibodies titers.•Long-term humoral and cellular immunity demonstrated here, supports the single-dose HAV strategy. Infants’ universal hepatitis A virus (HAV) single-dose vaccination has been highly effective for controlling HAV infection in Argentina, and in other Latin-American countries that adopted that strategy. Although antibodies wane over time, this has not been associated with HAV outbreaks or breakthrough infections, suggesting a relevant role for memory immunity. This study assessed long term humoral and cellular immune memory response after an average of 12 years follow-up of HAV single-dose vaccination. We selected 81 HAV-single dose vaccinated individuals from a 2015 study, including 54 with unprotective (UAL) and 27 with protective antibody levels (PAL) against HAV. Humoral memory response was assessed by measuring anti-HAV antibody titers at admission in both groups, and 30 days after a booster dose in the UAL group. Flow cytometry analysis of peripheral blood mononuclear cell samples stimulated with HAV antigen was performed in 47/81 individuals (21 with PAL, 26 with UAL) to identify activated CD4 + memory T cells or CD8 + memory T cells. The results showed that 48/52 (92%) individuals from UAL group who completed follow up reached protective levels after booster dose. In the PAL group, anti-HAV Abs waned in 2/27 (7%) individuals lacking seroprotection, while in 25/27 (93%) Abs remained >10 mUI/mL. HAV-specific memory CD4 + T cells were detected in 25/47 (53.2%) subjects while HAV-specific memory CD8 + T cells were observed in 16/47 (34.04%) individuals. HAV-specific memory CD4+ and CD8+ T cell responses were detected in 11/21 (52.4%) and in 9/21 (42.9%) subjects with PAL and in 14/26 (53.8%) and in 7/26 (26.9%) individuals with UAL, showing that the presence of memory T-cells was independent of the level or presence of anti-HAV antibodies. Long-term immunity demonstrated in the present work, including or not antibody persistence, suggests that individuals with waned Ab titers may still be protected and supports the single-dose HAV strategy.

Introduction. Though Staphylococcus aureus is a major pathogen, vaccine trials have failed. In contrast, classswitched antibodies specific to S. aureus are common, implying immune memory formation and suggesting a large pool of S. aureus-reactive helper T-cells. Objective. To elucidate the cellular arm of S. aureus-specif, the T-cell response in humans was characterized. Methods. The proliferative response of human peripheral blood mononuclear cells (PBMCs) to S. aureus antigens and the frequency of S. aureus-specific T-cells were quantified by ³H-thymidine incorporation; cytokine release was measured by flow cytometry. Results. Staphylococcus aureus particles and extracellular proteins elicited pronounced proliferation in PBMCs of healthy adults. This reflected a memory response with high frequencies of T-cells being activated by single S. aureus antigens. The whole S. aureus-specific T-cell pool was estimated to comprise 3.6% of T-cells with 35-fold differences between individuals (range, 0.2%-5.7%). When exposed to S. aureus antigens, the T-cells released predominantly but not solely T helper (Th) 1/Th17 cytokines. Conclusions. The large number of S. aureus antigen-reactive memory T-lymphocytes is likely to influence the course of S. aureus infection. To enable rational vaccine design, the naturally acquired human T-cell memory needs to be explored at high priority.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019 prompted scientific, medical, and biotech communities to investigate infection- and vaccine-induced immune responses in the context of this pathogen. B-cell and antibody responses are at the center of these investigations, as neutralizing antibodies (nAbs) are an important correlate of protection (COP) from infection and the primary target of SARS-CoV-2 vaccine modalities. In addition to absolute levels, nAb longevity, neutralization breadth, immunoglobulin isotype and subtype composition, and presence at mucosal sites have become important topics for scientists and health policy makers. The recent pandemic was and still is a unique setting in which to study de novo and memory B-cell (MBC) and antibody responses in the dynamic interplay of infection- and vaccine-induced immunity. It also provided an opportunity to explore new vaccine platforms, such as mRNA or adenoviral vector vaccines, in unprecedented cohort sizes. Combined with the technological advances of recent years, this situation has provided detailed mechanistic insights into the development of B-cell and antibody responses but also revealed some unexpected findings. In this review, we summarize the key findings of the last 2.5 years regarding infection- and vaccine-induced B-cell immunity, which we believe are of significant value not only in the context of SARS-CoV-2 but also for future vaccination approaches in endemic and pandemic settings.

Acquiring protective immunity through vaccination is essential, especially for patients with type 2 diabetes who are vulnerable for adverse clinical outcomes during coronavirus disease 2019 (COVID-19) infection. Type 2 diabetes (T2D) is associated with immune dysfunction. Here, we evaluated the impact of T2D on the immunological responses induced by mRNA (BNT162b2) and inactivated (CoronaVac) vaccines, the two most commonly used COVID-19 vaccines. The study consisted of two parts. In Part 1, the sera titres of IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) alpha receptor binding domain ( RBD), their neutralizing capacity, and antigen-specific CD4 + T and CD8 + T cell responses at 3-6 months after vaccination were compared between BNT162b2 (n=60) and CoronaVac (n=50) vaccinees with or without T2D. Part 2 was a time-course study investigating the initial B and T cell responses induced by BNT162b2 among vaccinees (n=16) with or without T2D. Our data showed that T2D impaired both cellular and humoral immune responses induced by CoronaVac. For BNT162b2, T2D patients displayed a reduction in CD4 + T-helper 1 (Th1) differentiation following their first dose. However, this initial defect was rectified by the second dose of BNT162b2, resulting in comparable levels of memory CD4 + and CD8 + T cells, anti-RBD IgG, and neutralizing antibodies with healthy individuals at 3-6 months after vaccination. Hence, T2D influences the effectiveness of COVID-19 vaccines depending on their platform. Our findings provide a potential mechanism for the susceptibility of developing adverse outcomes observed in COVID-19 patients with T2D and received either CoronaVac or just one dose of BNT162b2.

The attentional boost effect (ABE) and action-induced memory enhancement (AIME) suggest that memory performance for target-paired items is superior to that for distractor-paired items when participants performed a target detection task and a memory encoding task simultaneously. Though the memory enhancement has been well established, the temporal dynamics of how the target detection task influenced memory encoding remains unclear. To investigate this, we manipulated the stimulus onset asynchrony (SOA) between detection stimuli and the words to be memorized using a remember/know study-test paradigm, and we focused primarily on memory performance for the words that appeared after the detection response. The results showed that target-paired memory enhancement was robust from SOA = 0 s to SOA = 0.75 s, but was not significant when examined by itself in Experiment 1A or weakened in Experiment 2 and the conjoint analysis when SOA = 1 s, which were only observed in R responses. The post-response memory enhancement still existed when there was no temporal overlap between the word and target, similar to the magnitude of memory enhancement observed with temporal overlap. These results supported the view that target-paired memory enhancement (recollection rather than familiarity) occurred irrespective of whether the items appeared simultaneously with the targets or within a short period after the response, and the temporal overlap of the word and target was not necessary for post-response memory enhancement.

[This corrects the article DOI: 10.3389/fimmu.2024.1438371.].

Human Salmonella infections pose significant public health challenges globally, primarily due to low diagnostic yield of systemic infections, emerging and expanding antibiotic resistance of both the typhoidal and non-typhoidal Salmonella strains and the development of asymptomatic carrier state that functions as a reservoir of infection in the community. The limited long-term efficacy of the currently licensed typhoid vaccines, especially in smaller children and non-availability of vaccines against other Salmonella serovars necessitate active research towards developing a multivalent vaccine with wider coverage of protection against pathogenic Salmonella serovars. We had earlier reported immunogenicity and protective efficacy of a subunit vaccine containing a recombinant outer membrane protein (T2544) of Salmonella Typhi in a mouse model. This was achieved through the robust induction of serum IgG, mucosal secretory IgA and Salmonella -specific cytotoxic T cells as well as memory B and T cell response. Here, we report the development of a glycoconjugate vaccine, containing high molecular weight complexes of Salmonella Typhimurium O-specific polysaccharide (OSP) and recombinant T2544 that conferred simultaneous protection against S. Typhi, S. Paratyphi, S. Typhimurium and cross-protection against S. enteritidis in mice. Our findings corroborate with the published studies that suggested the potential of Salmonella OSP as a vaccine antigen. The role of serum antibodies in vaccine-mediated protection is suggested by rapid seroconversion with high titers of serum IgG and IgA, persistently elevated titers after primary immunization along with a strong antibody recall response with higher avidity serum IgG against both OSP and T2544 and significantly raised SBA titers of both primary and secondary antibodies against different Salmonella serovars. Elevated intestinal secretory IgA and bacterial motility inhibition by the secretory antibodies supported their role as well in vaccine-induced protection. Finally, robust induction of T effector memory response indicates long term efficacy of the candidate vaccine. The above findings coupled with protection of vaccinated animals against multiple clinical isolates confirm the suitability of OSP-rT2544 as a broad-spectrum candidate subunit vaccine against human infection due to typhoidal and non-typhoidal Salmonella serovars.

The invasive fungal infections (IFIs) are a major cause of mortality due to infectious disease worldwide. Majority of the IFIs are caused by opportunistic fungi including Candida , Aspergillus and Cryptococcus species. Lack of approved antifungal vaccines and the emergence of antifungal drug-resistant strains pose major constraints in controlling IFIs. A comprehensive understanding of the host immune response is required to develop novel fungal vaccines to prevent death from IFIs. In this review, we have discussed the challenges associated with the development of antifungal vaccines. We mentioned how host-pathogen interactions shape immunological memory and development of long-term protective immunity to IFIs. Furthermore, we underscored the contribution of long-lived innate and adaptive memory cells in protection against IFIs and summarized the current vaccine strategies.

The objective of cancer immunotherapy is to prime the host's immune system to recognize and attack malignant tumor cells. IMO-2125, a Toll-like receptor 9 (TLR9) agonist, exhibited potent antitumor effects in the murine syngeneic A20 lymphoma and the CT26 colon carcinoma models. IMO-2125 exhibited superior A20 antitumor activity when injected intratumorally (i.t.) compared with equivalent subcutaneous doses. In mice bearing dual CT26 grafts, the i.t. injection of right flank tumors elicited infiltration of cluster of differentiation (CD)3+ T lymphocytes into tumors, resulting in the regression of injected and uninjected left flank tumors. Depletion of CD8+, but not CD4+, T-cells abrogated the IMO-2125-mediated antitumor response, suggesting that CD8+ lymphocytes are required for the antitumor activity. In mice harboring right flank CT26 and left flank β-galactosidase (β-gal)-expressing CT26.CL25 grafts, the i.t. administration of IMO-2125 to the CT26 graft resulted in potent and dose-dependent antitumor activity against the two grafts. Splenic T-cells isolated from these mice responded to AH1 antigen (present in the two tumors) and β-gal antigen (present only in CT26. CL25) in an interferon γ enzyme-linked immunospot assay, suggesting the clonal expansion of T-cells directed against antigens from the two tumors. Mice with ablated CT26 tumors by previous IMO-2125 treatment rejected re-implanted CT26 tumor cells, but not A20 tumor cells, demonstrating that the initial IMO-2125 treatment created a long-lived tumor-specific immune memory of CT26 antigens. A quantitative increase in CD3+ T lymphocytes in injected A20 tumors and an upregulation of selected checkpoint genes, including indoleamine 2,3-dioxygenase (IDO)-1, IDO-2, programmed cell death protein-1 (PD-1); programmed cell death protein ligand 1 (PD-L1), carcinoembryonic antigen-related cell adhesion molecule 1, tumor necrosis factor receptor superfamily member 4 (OX40), OX40 ligand, T-cell immunoglobulin and mucin-domain-containing 3 protein, lymphocyte-activation gene 3, cytotoxic T-lymphocyte-associated protein 4, were observed following IMO-2125 treatment. IMO-2125 also increased immune checkpoint gene expression in injected and uninjected contralateral CT26 tumors, suggesting that the co-administration of anti-CTLA-4, anti-PD-1 or anti-PD-L1 therapies with IMO-2125 may provide additional therapeutic efficacy.

Arabidopsis plants subjected to a daily dehydration stress and watered recovery cycle display physiological and transcriptional stress memory. Previously stressed plants have stomatal apertures that remain partially closed during a watered recovery period, facilitating reduced transpiration during a subsequent dehydration stress. Guard cells (GCs) display transcriptional memory that is similar to that in leaf tissues for some genes, but display GC‐specific transcriptional memory for other genes. The rate‐limiting abscisic acid (ABA) biosynthetic genes NINE‐CIS‐EPOXYCAROTENOID DIOXYGENASE 3 (NCED3) and ALDEHYDE OXIDASE 3 (AAO3) are expressed at much higher levels in GCs, particularly during the watered recovery interval, relative to their low levels in leaves. A genetic analysis using mutants in the ABA signaling pathway indicated that GC stomatal memory is ABA‐dependent, and that ABA‐dependent SNF1‐RELATED PROTEIN KINASE 2.2 (SnRK2.2), SnRK2.3 and SnRK2.6 have distinguishable roles in the process. SnRK2.6 is more important for overall stomatal control, while SnRK2.2 and SnRK2.3 are more important for implementing GC stress memory in the subsequent dehydration response. Collectively, our results support a model of altered ABA production in GCs that maintains a partially closed stomatal aperture during an overnight watered recovery period.