Protective Humoral Immunity Research Articles

Ablation of regulatory T cells lead to compromised quality of humoral immunity to SA14-14-2 live attenuated Japanese encephalitis vaccine

Abstract Japanese encephalitis (JE) virus is the leading cause of encephalitis in Asia and the western Pacific. Most people infected with JE do not develop symptoms or have only mild symptoms. However, few infected people develop encephalitis and about 1 in 4 cases are fatal. Currently there is no treatment for JE however the vaccines are available. One of the most widely used vaccine against JE is live attenuated SA14-14-2, which is recommended for children and adults. However, less is known about the mechanism by which the vaccine induces protective immunity. We previously found that vaccine-induced CD4+ T cells play crucial role both in protection and in the development of protective humoral immunity. Here, we attempted to understand the role of CD4+ T cell subsets, mainly regulatory T cells (Tregs), in the mechanism of protection conferred by the vaccine. To address this, we used the Treg depletion mouse model and the TCRb −/−mouse as challenge model. We observed that depletion of Tregs lead to enhancement in germinal centre (GC) reaction to vaccine. We found a significant increase in GC-Tfh cells and GC-B cells in Treg ablation condition. We also found an increase in the magnitude of antibodies in response to vaccine particularly the IgG1 isotype. However, as marked by FRNT and the challenge studies, the neutralizing potential of the antibodies was compromised in Treg depleted condition. Altogether, the data suggest that the exclusion of Tregs may enhance the cellular and humoral response, however, that will negatively impact the protective quality of humoral immunity. Overall understanding the immunological mechanism of protective immunity conferred by this vaccine will be essential key for rational design of vaccine against JE or other flaviviruses. NII

Handheld NIR-to-NIR Platform for on-site evaluating protective neutralizing antibody against SARS-CoV-2 ancestral strain and Omicron variant after vaccination or infection

Lateral flow assays (LFAs) are promising points-of-care tests, playing a vital role in diseases screening, diagnosis and surveillance. However, development of portable, cheap, and smart LFAs platform for sensitive and accurate quantification of disease biomarkers in complex media is challenging. Here, a cheap handheld device was developed to realize on-site detection of disease biomarkers by Nd3+/Yb3+ co-doped near-infrared (NIR)-to-NIR downconversion nanoparticles (DCNPs) based LFA. Its sensitivity is at least 8-fold higher for detecting NIR light signal from Nd3+/Yb3+ co-doped nanoparticles than conventional expensive InGaAs camera based detection platform. Additionally, we enhance NIR quantum yield of Nd3+/Yb3+ co-doped nanoparticles up to 35.5% via simultaneous high dopant of sensitizer ions Nd3+ and emitter ions Yb3+. Combination of NIR-to-NIR handheld detection device and ultra-bright NIR emitting NaNbF4:Yb60%@NaLuF4 nanoparticle probe allows the detection sensitivity of SARS-CoV-2 ancestral strain and Omicron variants specific neutralizing antibodies LFA up to the level of commercial enzyme linked immunosorbent assay kit. Furthermore, by this robust method, enhanced neutralizing antibodies against SARS-CoV-2 ancestral strain and Omicron variants are observed in healthy participants with Ad5-nCoV booster on top of two doses of inactivated vaccine. This NIR-to-NIR handheld platform provides a promising strategy for on-site evaluating protective humoral immunity after SARS-CoV-2 vaccination or infection.

Glycosylated nanoparticle-based PfCSP vaccine confers long-lasting antibody responses and sterile protection in mouse malaria model

The development of an effective and durable vaccine remains a central goal in the fight against malaria. Circumsporozoite protein (CSP) is the major surface protein of sporozoites and the target of the only licensed Plasmodium falciparum (Pf) malaria vaccine, RTS,S/AS01. However, vaccine efficacy is low and short-lived, highlighting the need for a second-generation vaccine with superior efficacy and durability. Here, we report a Helicobacter pylori apoferritin-based nanoparticle immunogen that elicits strong B cell responses against PfCSP epitopes that are targeted by the most potent human monoclonal antibodies. Glycan engineering of the scaffold and fusion of an exogenous T cell epitope enhanced the anti-PfCSP B cell response eliciting strong, long-lived and protective humoral immunity in mice. Our study highlights the power of rational vaccine design to generate a highly efficacious second-generation anti-infective malaria vaccine candidate and provides the basis for its further development.

Vaccination against SARS-CoV-2 using extracellular blebs derived from spike protein-expressing dendritic cells.

COVID-19 has caused significant morbidity and mortality worldwide but also accelerated the clinical use of emerging vaccine formulations. To address the current shortcomings in the prevention and treatment of SARS-CoV-2 infection, this study developed a novel vaccine platform that closely mimics dendritic cells (DCs) in antigen presentation and T-cell stimulation in a cell-free and tunable manner. Genetically engineered DCs that express the SARS-CoV-2 spike protein (S) were chemically converted into extracellular blebs (EBs). The resulting EBs elicited potentially protective humoral immunity in vivo, indicated by the production of antibodies that potently neutralized S-pseudotyped virus, presenting EBs as a promising and safe vaccine.

MAIT cells activate dendritic cells to promote TFH cell differentiation and induce humoral immunity

Protective immune responses against respiratory pathogens, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus, are initiated by the mucosal immune system. However, most licensed vaccines are administered parenterally and are largely ineffective at inducing mucosal immunity. The development of safe and effective mucosal vaccines has been hampered by the lack of a suitable mucosal adjuvant. In this study we explore a class of adjuvant that harnesses mucosal-associated invariant T (MAIT) cells. We show evidence that intranasal immunization of MAIT cell agonists co-administered withprotein, including the spike receptor binding domain from SARS-CoV-2 virus and hemagglutinin from influenza virus, induce protective humoral immunity and immunoglobulin A production. MAIT cell adjuvant activity is mediated by CD40L-dependent activation of dendritic cells and subsequent priming of T follicular helper cells. In summary, we show that MAIT cells are promising vaccine targets that can be utilized as cellular adjuvants in mucosal vaccines.

Blunted humoral immune response to the fourth dose of BNT162b2 COVID-19 vaccine in patients undergoing hemodialysis.

We aimed to investigate the impact of a fourth dose of BNT162b2 vaccine (Comirnaty®, Pfizer-BioNTech) on anti-SARS-CoV-2 (anti-S IgG) antibody titers in patients receiving hemodialysis (HD) and healthcare workers (HCWs). A multi-institutional retrospective study at five dialysis clinics in Japan was conducted using 238 HD patients and 58 HCW controls who received four doses of the BNT162b2 mRNA vaccine. Anti-S IgG titers were measured at 1, 3, and 6months after the second dose, at 1 and 5/6months after the third dose, and at 1month after the fourth dose of vaccine. The log anti-S IgG titers of the HD patients after the second vaccination were significantly lower than those of the control group, but equalized 1month after the third vaccination: 9.94 (95% CI 9.82-10.10) vs. 9.81 (95% CI 9.66-9.96), (P = 0.32). In both groups, the fold-increase in anti-S IgG titers was significantly lower after the fourth dose than after the third dose of vaccine. In addition, there was a strong negative correlation between antibody titers 1month after the fourth vaccination and antibody titers immediately before the vaccination. In both groups, the waning rate of anti-S IgG titers from the post-vaccination peak level after the third vaccine dose was significantly slower than that after the second dose. These findings suggest that the humoral immune response was blunted after the fourth dose of the conventional BNT162b2 vaccine. However, multiple vaccinations could extend the window of humoral immune protection.

Single-cell analysis reveals dynamics of human B cell differentiation and identifies novel B and antibody-secreting cell intermediates.

Differentiation of B cells into antibody-secreting cells (ASCs) is a key process to generate protective humoral immunity. A detailed understanding of the cues controlling ASC differentiation is important to devise strategies to modulate antibody formation. Here, we dissected differentiation trajectories of human naive B cells into ASCs using single-cell RNA sequencing. By comparing transcriptomes of B cells at different stages of differentiation from an in vitro model with ex vivo B cells and ASCs, we uncovered a novel pre-ASC population present ex vivo in lymphoid tissues. For the first time, a germinal-center-like population is identified in vitro from human naive B cells and possibly progresses into a memory B cell population through an alternative route of differentiation, thus recapitulating in vivo human GC reactions. Our work allows further detailed characterization of human B cell differentiation into ASCs or memory B cells in both healthy and diseased conditions.

Age-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose.

The emergence of the SARS-CoV-2 Omicron sublineages resulted in increased transmission rates and reduced protection from vaccines. To counteract these effects, multiple booster strategies were used in different countries, although data comparing their efficiency in improving protective immunity remain sparse, especially among vulnerable populations, including older adults. The inactivated CoronaVac vaccine was among the most widely distributed vaccine worldwide and was essential in the early control of SARS-CoV-2-related hospitalizations and deaths. However, it is not well understood whether homologous versus heterologous booster doses in those fully vaccinated with CoronaVac induce distinct humoral responses or whether these responses vary across age groups. We analyzed plasma antibody responses from CoronaVac-vaccinated younger or older individuals who received a homologous CoronaVac or heterologous BNT162b2 or ChAdOx1 booster vaccine. All three evaluated boosters resulted in increased virus-specific IgG titers 28 days after the booster dose. However, we found that both IgG titers against SARS-CoV-2 Spike or RBD and neutralization titers against Omicron sublineages were substantially reduced in participants who received homologous CoronaVac compared with the heterologous BNT162b2 or ChAdOx1 booster. This effect was specifically prominent in recipients >50 years of age. In this group, the CoronaVac booster induced low virus-specific IgG titers and failed to elevate neutralization titers against any Omicron sublineage. Our results point to the notable inefficiency of CoronaVac immunization and boosting in mounting protective antiviral humoral immunity, particularly among older adults, during the Omicron wave. These observations also point to benefits of heterologous regimens in high-risk populations fully vaccinated with CoronaVac.

The Role of Immunity in the Pathogenesis of SARS-CoV-2 Infection and in the Protection Generated by COVID-19 Vaccines in Different Age Groups.

This study aims to review the available data regarding the central role of immunity in combating SARS-CoV-2 infection and in the generation of protection by vaccination against COVID-19 in different age groups. Physiologically, the immune response and the components involved in it are variable, both functionally and quantitatively, in neonates, infants, children, adolescents, and adults. These immunological differences are mirrored during COVID-19 infection and in the post-vaccination period. The outcome of SARS-CoV-2 infection is greatly dependent on the reaction orchestrated by the immune system. This is clearly obvious in relation to the clinical status of COVID-19 infection, which can be symptomless, mild, moderate, or severe. Even the complications of the disease show a proportional pattern in relation to the immune response. On the contrary, the commonly used anti-COVID-19 vaccines generate protective humoral and cellular immunity. The magnitude of this immunity and the components involved in it are discussed in detail. Furthermore, many of the adverse effects of these vaccines can be explained on the basis of immune reactions against the different components of the vaccines. Regarding the appropriate choice of vaccine for different age groups, many factors have to be considered. This is a cornerstone, particularly in the following age groups: 1 day to 5 years, 6 to 11 years, and 12 to 17 years. Many factors are involved in deciding the route, doses, and schedule of vaccination for children. Another important issue in this dilemma is the hesitancy of families in making the decision about whether to vaccinate their children. Added to these difficulties is the choice by health authorities and governments concerning whether to make children's vaccination compulsory. In this respect, although rare and limited, adverse effects of vaccines in children have been detected, some of which, unfortunately, have been serious or even fatal. However, to achieve comprehensive control over COVID-19 in communities, both children and adults have to be vaccinated, as the former group represents a reservoir for viral transmission. The understanding of the various immunological mechanisms involved in SARS-CoV-2 infection and in the preparation and application of its vaccines has given the sciences a great opportunity to further deepen and expand immunological knowledge. This will hopefully be reflected positively on other diseases through gaining an immunological background that may aid in diagnosis and therapy. Humanity is still in continuous conflict with SARS-CoV-2 infection and will be for a while, but the future is expected to be in favor of the prevention and control of this disease.

T follicular helper 17 (Tfh17) cells are superior for immunological memory maintenance.

A defining feature of successful vaccination is the ability to induce long-lived antigen-specific memory cells. T follicular helper (Tfh) cells specialize in providing help to B cells in mounting protective humoral immunity in infection and after vaccination. Memory Tfh cells that retain the CXCR5 expression can confer protection through enhancing humoral response upon antigen re-exposure but how they are maintained is poorly understood. CXCR5+ memory Tfh cells in human blood are divided into Tfh1, Tfh2, and Tfh17 cells by the expression of chemokine receptors CXCR3 and CCR6 associated with Th1 and Th17, respectively. Here, we developed a new method to induce Tfh1, Tfh2, and Tfh17-like (iTfh1, iTfh2, and iTfh17) mouse cells in vitro. Although all three iTfh subsets efficiently support antibody responses in recipient mice with immediate immunization, iTfh17 cells are superior to iTfh1 and iTfh2 cells in supporting antibody response to a later immunization after extended resting in vivo to mimic memory maintenance. Notably, the counterpart human Tfh17 cells are selectively enriched in CCR7+ central memory Tfh cells with survival and proliferative advantages. Furthermore, the analysis of multiple human cohorts that received different vaccines for HBV, influenza virus, tetanus toxin or measles revealed that vaccine-specific Tfh17 cells outcompete Tfh1 or Tfh2 cells for the persistence in memory phase. Therefore, the complementary mouse and human results showing the advantage of Tfh17 cells in maintenance and memory function supports the notion that Tfh17-induced immunization might be preferable in vaccine development to confer long-term protection.

Leishmania donovani induces CD300a expression to dampen effector properties of CD11c+ dendritic and antigen activated CD8+ T cells

CD8+ T cells are an important regiment of adaptive immunity that play a decisive role in elimination of many species of Leishmania parasite from the host. In visceral leishmaniasis, caused by L. donovani, the loss of CD8+ T cells function has been found associated with augmented pathogenesis. The factors determining CD8+ T cells activation and function against Leishmania antigens are largely unknown. In this study, we investigated the role of an immune inhibitory receptor, CD300a, on the effector properties of dendritic cells and CD8+ T cells. We observed that the Leishmania regulates the effectors function of CD8+ T cells by increasing CD300a expression on CD11c+ dendritic cells. The abrogation of CD300a signaling in parasites infected animals induced CD8+ T cell abilities to produce IFN-γ, TNF-α and also helped them to acquire desired multifunctionality. The CD300a receptor blocking also enhanced the number of CD8+ T cells memory phenotypes at the early days of infection, suggesting its potential beneficial role in vaccine induced immunity. We also observed significantly enhanced levels of pro-inflammatory cytokines in the spleen of CD300a blocked infected animals with concomitant reduced spleen parasite load. Additionally, the abrogation of CD300a signals in the infected animals helped in establishing Th1 type protective humoral immunity with significantly elevated levels of IgG2a antibodies. Since CD8+ T cells are an important determinant of vaccine induced immunity against leishmaniasis, the findings corroborate the potential of CD300a in vaccine induced immunity and thus require further attention.

Annual two-dose tetanus toxoid vaccination induces protective humoral immunity to all age groups of rhesus macaques.

A tetanus outbreak occurred during 2014-2015 in the rhesus macaques reared in an open enclosure in our facility. As the soil of the facility was suspected to be contaminated with Clostridium tetani spores, there was a risk of further tetanus occurring among the macaques. To protect them from tetanus, a tetanus toxoid vaccination was recommended; however, the vaccinated elderly animals might not be effectively protected due to insufficient humoral immune responses. Hence, we evaluated the dynamics of antibody responses among rhesus macaques of all age groups vaccinated with two-dose tetanus toxoid at a 1-year interval during a 3-year follow-up study. The vaccination developed anti-tetanus toxin-specific antibodies in animals of all age groups, the antibody levels peaked 1 year after the second vaccination, and the peak levels decreased with age. However, the levels among elderly individuals (aged ≥13 years) were still higher than the threshold level, which was supposed to protect them from tetanus development. Although the rhesus macaques in our facility had a risk of occasional exposure to the spores due to the outbreak, no incidence of tetanus has ever occurred to date. These results indicate that the vaccination protocol is effective in protecting not only younger but also older animals from tetanus.

PD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection

T cell-B cell interaction is the key immune response to protect the host from severe viral infection. However, how Tcells support B cells to exert protective humoral immunity in humans is not well understood. Here, we use COVID-19 as a model of acute viral infections and analyze CD4+ Tcell subsets associated with plasmablast expansion and clinical outcome. Peripheral helper Tcells (Tph cells; denoted as PD-1highCXCR5-CD4+ Tcells) are significantly increased, as are plasmablasts. Tph cells exhibit "B cell help" signatures and induce plasmablast differentiation invitro. Interestingly, expanded plasmablasts show increased CXCR3 expression, which is positively correlated with higher frequency of activated Tph cells and better clinical outcome. Mechanistically, Tph cells help B cell differentiation and produce more interferon γ (IFNγ), which induces CXCR3 expression on plasmablasts. These results elucidate a role for Tph cells in regulating protective Bcell response during acute viral infection.

Comparison between the homologous BNT162b2 and the heterologous Gam-COVID-Vac/BNT162b2 vaccine regimen in republic of North Macedonia

The medical and socio-economic consequences that stemmed from the COVID-19 pandemic, forced the healthcare policymakers in Republic of North Macedonia to rely on five different vaccines against the SARS-CoV-2 virus, in order to reach a satisfactory level of herd immunity. It is here where we got the idea to compare the heterologous Gam-COVID-Vac/BNT162b2 regimen to the homologous BNT162b2 regimen, with our main focus being the immunogenicity differences between the two of them. Additionally, we researched the variation in humoral immune response relative to age strata; the reactogenicity differences; and discrepancies in SARS-CoV-2 infection incidence between the two regimens. To achieve this, antibody titers in sera samples from fifty-three (53) healthcare workers, divided in heterologous and homologous group, were analysed at six different time checkpoints. Our results showed robust immunogenic response after the administration of the booster dose (4. 2-fold increase in antibody titers), followed by a slower-waning humoral immune protection in the heterologous regimen, compared to the homologous BNT162b2 schedule, furthermore confirmed by non-inferiority testing (Geometric Mean Ratio=0,98) at the final checkpoint. That, coupled with the similar reactogenicity (p=0,767) of both regimens, imply that the Gam-COVID-Vac/BNT162b2 combination might be a feasible approach in the effort to contain the COVID-19 pandemic.

491. Characterizing the Association of Pre-Existing Cytomegalovirus (CMV)-specific Humoral Immunity with CMV Reactivation Risk after Hematopoietic Cell Transplantation (HCT)

Abstract Background There is renewed interest in CMV-specific humoral immune protection due to recent murine data suggesting that strain-specific antibodies may inhibit CMV cell-to-cell spread (Science. 2019; 363:288). To characterize the nature of antibody protection against CMV after HCT, we tested pre-HCT sera in a cohort of CMV D-R+ allogeneic HCT recipients from the pre-letermovir era using VirScan, a technology that measures pathogen-specific humoral immunity (IgG) at the epitope level. Methods Patients (age 0-70 years) who received 1st, myeloablative, HCT for acute leukemia or myelodysplastic syndrome and who underwent PCR surveillance and preemptive therapy were included. VirScan was used on sera collected pre-HCT. Cumulative incidence curves and multivariable Cox regression analyses were used to determine the association of pre-HCT CMV antibody epitopes scores with CMV reactivation (any, >150 IU/mL, >500 IU/mL) in the first 8 weeks post-HCT. Results 170 CMV D-R+ HCT recipients were tested a median of 26 days (range 7-37 days) prior to HCT and had a median of 37 CMV antibody epitopes (IQR 29-50 epitopes, range 14-77 epitopes). The cumulative incidence of CMV reactivation was higher in patients with greater pre-HCT CMV antibody epitopes at each evaluated PCR threshold (Figure 1) and the effect appeared more pronounced in adults (Figure 2). High (≥ 4th quartile vs. 1st quartile), pre-HCT CMV antibody epitopes were associated with an increased risk of any CMV reactivation (adjusted Hazard Ratio [aHR]=4.1, 95% confidence interval [CI] 2.1-7.7, p< 0.001) and at >150 IU/mL (aHR=3.0, 95% CI 1.4-6.5 p=0.006) after adjusting for age, HLA-matching, and pre-HCT T-cell depletion ( >150 IU/mL only). Figure 1Figure 2 Conclusion We observed a paradoxically increased risk of CMV reactivation in patients with high pre-HCT CMV VirScan scores. It is possible that pre-HCT CMV-specific humoral immunity as measured by VirScan is reflective of the burden of latent CMV or that CMV-specific antibodies may mediate antibody-dependent enhancement after HCT and thus facilitate reactivation. Future studies are needed to validate our findings in diverse cohorts and to elucidate the underlying mechanism of increased VirScan scores and associated risks of CMV reactivation. Disclosures Rachel A. Bender Ignacio, MD, MPH, Abbvie: Advisor/Consultant|SeaGen: Advisor/Consultant Joshua A. Hill, MD, Allovir: Advisor/Consultant|Allovir: Grant/Research Support|Covance/CSL: Advisor/Consultant|CRISPR: Advisor/Consultant|Deverra: Grant/Research Support|Gilead: Grant/Research Support|Karius: Advisor/Consultant|Karius: Grant/Research Support|Merck: Grant/Research Support|Octapharma: Advisor/Consultant|OptumHealth: Advisor/Consultant|Oxford Immunotec: Grant/Research Support|Pfizer: Advisor/Consultant|Symbio: Advisor/Consultant|Takeda: Advisor/Consultant Geoffrey Hill, M.D., FRACP, FRCPA, Applied Molecular Transport: Grant/Research Support|Compass Therapeutics: Grant/Research Support|Generon Corporation: Advisor/Consultant|Heat Biologics: Grant/Research Support|iTeos Therapeutics: Advisor/Consultant|iTeos Therapeutics: Grant/Research Support|Laevoroc Oncology: Grant/Research Support|NapaJen Pharma: Advisor/Consultant|Neoleukin Therapeutics: Advisor/Consultant|Serplus Technology: Grant/Research Support|Syndax Pharmaceuticals: Grant/Research Support Michael J. Boeckh, MD PhD, Allovir: Advisor/Consultant|Amazon: Grant/Research Support|Ansun Biopharma: Grant/Research Support|EvrysBio: Advisor/Consultant|Gates Ventures: Grant/Research Support|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|Helocyte: Advisor/Consultant|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kyorin Pharmaceuticals: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Regeneron: Grant/Research Support|ReViral: Advisor/Consultant|Symbio: Advisor/Consultant|Takeda: Grant/Research Support|Vir Biotechnology: Advisor/Consultant|Vir Biotechnology: Grant/Research Support.

Primary exposure to SARS-CoV-2 variants elicits convergent epitope specificities, immunoglobulin V gene usage and public B cell clones

An important consequence of infection with a SARS-CoV-2 variant is protective humoral immunity against other variants. However, the basis for such cross-protection at the molecular level is incompletely understood. Here, we characterized the repertoire and epitope specificity of antibodies elicited by infection with the Beta, Gamma and WA1 ancestral variants and assessed their cross-reactivity to these and the more recent Delta and Omicron variants. We developed a method to obtain immunoglobulin sequences with concurrent rapid production and functional assessment of monoclonal antibodies from hundreds of single B cells sorted by flow cytometry. Infection with any variant elicited similar cross-binding antibody responses exhibiting a conserved hierarchy of epitope immunodominance. Furthermore, convergent V gene usage and similar public B cell clones were elicited regardless of infecting variant. These convergent responses despite antigenic variation may account for the continued efficacy of vaccines based on a single ancestral variant.

Splenic-targeting biomimetic nanovaccine for elevating protective immunity against virus infection

BackgroundThe prevalence of viral infectious diseases has become a serious threat to public safety, economic and social development. Vaccines have been served as the most effective platform to prevent virus transmission via the activation of host immune responses, while the low immunogenicity or safety, the high cost of production, storage, transport limit their effective clinical application. Therefore, there is a need to develop a promising strategy to improve the immunogenicity and safety of vaccines.MethodsWe developed a splenic-targeting biomimetic nanovaccine (NV) that can boost protective humoral and cellular immunity against african swine fever virus (ASFV) infection. The universal PLGA nanoparticles (CMR-PLGA/p54 NPs) coated with mannose and CpG (TLR9 agonist) co-modified red blood cell (RBC) membrane were prepared, which comprised a viral antigen (p54) and can be served as a versatile nanovaccine for elevating protective immunity.ResultsCMR-PLGA/p54 NVs could be effectively uptaken by BMDC and promoted BMDC maturation in vitro. After subcutaneous immunization, antigen could be effectively delivered to the splenic dendritic cells (DCs) due to the splenic homing ability of RBC and DC targeting capacity of mannose, which promoted antigen presentation and DCs maturation, and further elicited higher levels of cytokines secretion and specific IgG titers, CD4+ and CD8+ T cells activation and B maturation. Moreover, NVs demonstrated notable safety during the immunization period.ConclusionsThis study demonstrates the high potential of CMR-PLGA NPs as vaccine delivery carriers to promote humoral and cellular immune responses, and it provides a promising strategy to develop safe and effective vaccines against viral infectious diseases.

Long-Term Effectiveness of Hepatitis B Vaccination in the Protection of Healthcare Students in Highly Developed Countries: A Systematic Review and Meta-Analysis.

Hepatitis B virus represents an important global health problem. In highly developed countries, mass vaccination campaigns of newborns in recent decades have drastically reduced the proportion of carriers. However, workers exposed to blood and body fluids, including healthcare students, can be at risk of exposure. In order to assess the proportion of susceptible individuals in the specific population of healthcare students in highly developed countries, a systematic review and meta-analysis was performed to summarize the evidence on the persistence of humoral immune protection induced by the primary cycle of hepatitis B vaccination, as well as the proportion of true non-responders. Forty-six studies were included in the final analysis (52,749 participants). Overall, the seroprotection prevalence at the pre-exposure assessment was equal to 73.8% (95% CI 69.1-78.0); the prevalence of anamnestic response following the administration of a challenge dose was 90.9% (95% CI 87.7-93.3), demonstrating a high proportion of persistence of vaccination-induced immunity. Among those without evidence of anamnestic response, 5.0% (95% CI 2.1-11.5) were non-responders following the completion of a secondary immunization cycle. These findings demonstrate that the majority of healthcare students vaccinated with the complete HBV primary cycle maintain an effective humoral immunity against this pathogen for over two decades.

Dynamics of B-Cell Responses after SARS-CoV-2 Vaccination in Spain.

The high mortality rate due to COVID-19 has necessitated the mass vaccination against SARS-CoV-2 to induce protective humoral and cellular immunity. (1) Objective: To study the dynamics of SARS-CoV-2-specific B cells after two doses of the Pfizer-BioNTech SARS-CoV-2 vaccine. (2) Methods: Immunophenotyping and cellular cultures were used to determine the kinetics of B-cell subpopulations and vaccine responses in volunteers before and seven days, three months and seven months after the second dose in Spain (n = 19). (3) Results: Seven days after immunisation, memory B cells and plasmablasts expressing receptors for factors implicated in the maturation of plasma cells were augmented in blood. Three months after vaccination, SARS-CoV-2 spike-specific plasmablasts disappeared from circulation while spike-specific memory-B cells circulated, with heterogeneous dynamics among individuals. (4) Conclusion: After vaccination, specific plasmablasts equipped with receptors for maturation factors were quickly generated and disappeared rapidly from the blood, while specific memory B cells circulated for at least seven months.

A potential association between obesity and reduced effectiveness of COVID-19 vaccine-induced neutralizing humoral immunity.

Due to the adverse effects of obesity on host immunity, this study investigated the effectiveness of COVID‐19 vaccines (BNT162b2, ChAdOx‐nCov‐2019, and mRNA‐1273) in inducing anti‐SARS‐CoV‐2 Spike (S) neutralizing antibodies among individuals with various obesity classes (class I, II, III, and super obesity). Sera from vaccinated obese individuals (n = 73) and normal BMI controls (n = 46) were subjected to S‐based enzyme‐linked immunosorbent assay (ELISA) and serum‐neutralization test (SNT) to determine the prevalence and titer of anti‐SARS‐CoV‐2 neutralizing antibodies. Nucleocapsid‐ELISA was also utilized to distinguish between immunity acquired via vaccination only versus vaccination plus recovery from infection. Data were linked to participant demographics including age, gender, past COVID‐19 diagnosis, and COVID‐19 vaccination profile. S‐based ELISA demonstrated high seroprevalence rates (>97%) in the study and control groups whether samples with evidence of past infection were included or excluded. Interestingly, however, SNT demonstrated a slightly significant reduction in both the rate and titer of anti‐SARS‐CoV‐2 neutralizing antibodies among vaccinated obese individuals (60/73; 82.19%) compared to controls (45/46; 97.83%). The observed reduction in COVID‐19 vaccine‐induced neutralizing humoral immunity among obese individuals occurs independently of gender, recovery from past infection, and period from last vaccination. Our data suggest that COVID‐19 vaccines are highly effective in inducing protective humoral immunity. This effectiveness, however, is potentially reduced among obese individuals which highlight the importance of booster doses to improve their neutralizing immunity. Further investigations on larger sample size remain necessary to comprehensively conclude about the effect of obesity on COVID‐19 vaccine effectiveness on humoral immunity induction.