Humoral and cellular immune memory to four COVID-19 vaccines.

Multiple COVID-19 vaccines, representing diverse vaccine platforms, successfully protect against symptomatic COVID-19 cases and deaths. Head-to-head comparisons of T cell, B cell, and antibody responses to diverse vaccines in humans are likely to be informative for understanding protective immunity against COVID-19, with particular interest in immune memory. Here, SARS-CoV-2-spike-specific immune responses to Moderna mRNA-1273, Pfizer/BioNTech BNT162b2, Janssen Ad26.COV2.S, and Novavax NVX-CoV2373 were examined longitudinally for 6 months 100% of individuals made memory CD4+ T cells, with cTfh and CD4-CTL highly represented after mRNA or NVX-CoV2373 vaccination. mRNA vaccines and Ad26.COV2.S induced comparable CD8+ T cell frequencies, though only detectable in 60-67% of subjects at 6 months. A differentiating feature of Ad26.COV2.S immunization was a high frequency of CXCR3+ memory B cells. mRNA vaccinees had substantial declines in antibodies, while memory T and B cells were comparatively stable. These results may also be relevant for insights against other pathogens.

Rational design of polymer-based particulate vaccine adjuvants.

Vaccination is considered one of the major milestones in modern medicine, facilitating the control and eradication of life-threatening infectious diseases. Vaccine adjuvants are a key component of many vaccines, serving to steer antigen-specific immune responses and increase their magnitude. Despite major advances in the field of adjuvant research over recent decades, our understanding of their mechanism of action remains incomplete. This hinders our capacity to further improve these adjuvant technologies, so addressing how adjuvants induce and control the induction of innate and adaptive immunity is a priority. Investigating how adjuvant physicochemical properties, such as size and charge, exert immunomodulatory effects can provide valuable insights and serve as the foundation for the rational design of vaccine adjuvants. Most clinically applied adjuvants are particulate in nature and polymeric particulate adjuvants present advantages due to stability, biocompatibility profiles, and flexibility in terms of formulation. These properties can impact on antigen release kinetics and biodistribution, cellular uptake and targeting, and drainage to the lymphatics, consequently dictating the induction of innate, cellular, and humoral adaptive immunity. A current focus is to apply rational design principles to the development of adjuvants capable of eliciting robust cellular immune responses including CD8+ cytotoxic T-cell and Th1-biased CD4+ T-cell responses, which are required for vaccines against intracellular pathogens and cancer. This review highlights recent advances in our understanding of how particulate adjuvants, especially polymer-based particulates, modulate immune responses and how this can be used as a guide for improved adjuvant design.

Proteomics Investigation of Diverse Serological Patterns in COVID-19.

Serum antibodies IgM and IgG are elevated during Coronavirus Disease 2019 (COVID-19) to defend against viral attacks. Atypical results such as negative and abnormally high antibody expression were frequently observed whereas the underlying molecular mechanisms are elusive. In our cohort of 144 COVID-19 patients, 3.5% were both IgM and IgG negative, whereas 29.2% remained only IgM negative. The remaining patients exhibited positive IgM and IgG expression, with 9.3% of them exhibiting over 20-fold higher titers of IgM than the others at their plateau. IgG titers in all of them were significantly boosted after vaccination in the second year. To investigate the underlying molecular mechanisms, we classed the patients into four groups with diverse serological patterns and analyzed their 2-year clinical indicators. Additionally, we collected 111 serum samples for TMTpro-based longitudinal proteomic profiling and characterized 1494 proteins in total. We found that the continuously negative IgM and IgG expression during COVID-19 were associated with mild inflammatory reactions and high T cell responses. Low levels of serum IgD, inferior complement 1 activation of complement cascades, and insufficient cellular immune responses might collectively lead to compensatory serological responses, causing overexpression of IgM. Serum CD163 was positively correlated with antibody titers during seroconversion. This study suggests that patients with negative serology still developed cellular immunity for viral defense and that high titers of IgM might not be favorable to COVID-19 recovery.

In-depth transcriptomic analysis of Anopheles gambiae hemocytes uncovers novel genes and the oenocytoid developmental lineage.

BACKGROUND: Hemocytes are immune cells that patrol the mosquito hemocoel and mediate critical cellular defense responses against pathogens. However, despite their importance, a comprehensive transcriptome of these cells was lacking because they constitute a very small fraction of the total cells in the insect, limiting the study of hemocyte differentiation and immune function. RESULTS: In this study, an in-depth hemocyte transcriptome was built by extensive bulk RNA sequencing and assembly of hemocyte RNAs from adult A. gambiae female mosquitoes, based on approximately 2.4 billion short Illumina and about 9.4 million long PacBio high-quality reads that mapped to the A. gambiae PEST genome (P4.14 version). A total of 34,939 transcripts were annotated including 4,020 transcripts from novel genes and 20,008 novel isoforms that result from extensive differential splicing of transcripts from previously annotated genes. Most hemocyte transcripts identified (89.8%) are protein-coding while 10.2% are non-coding RNAs. The number of transcripts identified in the novel hemocyte transcriptome is twice the number in the current annotation of the A. gambiae genome (P4.14 version). Furthermore, we were able to refine the analysis of a previously published single-cell transcriptome (scRNAseq) data set by using the novel hemocyte transcriptome as a reference to re-define the hemocyte clusters and determine the path of hemocyte differentiation. Unsupervised pseudo-temporal ordering using the Tools for Single Cell Analysis software uncovered a novel putative prohemocyte precursor cell type that gives rise to prohemocytes. Pseudo-temporal ordering with the Monocle 3 software, which analyses changes in gene expression during dynamic biological processes, determined that oenocytoids derive from prohemocytes, a cell population that also gives rise to the granulocyte lineage. CONCLUSION: A high number of mRNA splice variants are expressed in hemocytes, and they may account for the plasticity required to mount efficient responses to many different pathogens. This study highlights the importance of a comprehensive set of reference transcripts to perform robust single-cell transcriptomic data analysis of cells present in low abundance. The detailed annotation of the hemocyte transcriptome will uncover new facets of hemocyte development and function in adult dipterans and is a valuable community resource for future studies on mosquito cellular immunity.

Impaired acute-phase humoral immunity is the major factor predicting unfavorable outcomes in multiple myeloma patients with SARS-CoV-2 Omicron variants outbreak infection.

At the end of 2022, a huge tide of SARS-CoV-2 infection mainly Omicron BA.4/5 developed in China. Multiple myeloma (MM) patients suffered cancer deterioration and mortality from COVID-19, yet profound analyses of Omicron variants-induced immunity function are scarce. We presented a longitudinal study in 218 MM patients and 73 healthy controls (HCs), reporting the prognostic factors and dynamic humoral and cellular immune responses. Neutralizing antibody and interferon γ ELISpot assay of SARS-CoV-2 was tested at three time points: 2-4, 8-10, and 14-16 weeks after infections. Our data showed older age, active MM, relapsed/refractory MM (R/RMM), immunotherapy, comorbidity, and non-vaccination were risk factors associated with hospitalization. Severe humoral immunity impairment within 2-4 weeks was especially seen in patients with unvaccinated, older age, immunotherapy, R/RMM and comorbidities, while T-cell response was relatively intact. Although antibodies of Omicron variants reached positive levels in MM patients at 8-10 weeks, half lost effective antibody protection at 14-16 weeks. However, most seronegative patients (76.2% at 2-4 weeks, 83.3% at 8-10 weeks) could develop effective T-cell response. Notably, the inactivated wild-type vaccinated patients exhibited weaker humoral and cellular immunity only at 2-4 weeks, escalating to similar levels as those in HCs later. Our findings indicate impairment of humoral immunity at acute-phase after infection is the major factor correlated with hospitalization. One-month suspension of immune therapy is suggested to prevent serious infection. These results confirm the value of inactivated vaccine, but indicate the need for additional booster at 14-16 weeks after infection for high-risk MM population.

Enhancement of cellular immunity following needle-free vaccination of mice with SARS-CoV-2 spike protein.

The COVID-19 pandemic has highlighted the need for vaccines capable of providing rapid and robust protection. One way to improve vaccine efficacy is delivery via microarray patches, such as the Vaxxas high-density microarray patch (HD-MAP). We have previously demonstrated that delivery of a SARS-CoV-2 protein vaccine candidate, HexaPro, via the HD-MAP induces potent humoral immune responses. Here, we investigate the cellular responses induced by HexaPro HD-MAP vaccination. We found that delivery via the HD-MAP induces a type one biassed cellular response of much greater magnitude as compared to standard intramuscular immunization.

Rapid and high throughput assessment of cellular immunity against SARS-CoV-2 based on the ex vivo activation of genes in leukocyte assay with whole blood.

During the novel coronavirus outbreak and vaccine development, antibody production garnered major focus as the primary immunogenic response. However, cellular immunity's recent demonstration of comparable or greater significance in controlling infection demands the re-evaluation of the importance of T-cell immunity in SARS-CoV-2 infection. Here, we developed a novel assay, the ex vivo activation of genes in leukocytes (EAGL), which employs short-term whole blood stimulation with the LeukoComplete™ system, to measure ex vivo SARS-CoV-2-specific T cell responses (cellular immunity). This assay measures upregulated mRNA expression related to leukocyte activation 4 h after antigen stimulation. LeukoComplete™ system uses whole blood samples, eliminating the need for pretreatment before analysis. Furthermore, this system's high reproducibility is ensured through a series of operations from mRNA extraction to cDNA synthesis on a 96-well plate. In the performance evaluation using fresh blood from previously SARS-CoV-2-infected and COVID-19-vaccinated individuals, the EAGL assay had a comparable sensitivity and specificity to the ELISpot assay (EAGL: 1.000/1.000; ELISpot: 0.900/0.973). As a simple, high-throughput assay, the EAGL assay is also a quantitative test that is useful in studies with large sample numbers, such as monitoring new vaccine efficacies against novel coronaviruses or epidemiologic studies that require cellular immune testing during viral infection.

Effects of Skeleton Structure of Mesoporous Silica Nanoadjuvants on Cancer Immunotherapy.

Mesoporous silica nanoparticles (MSNs) have been widely praised as nanoadjuvants in vaccine/tumor immunotherapy thanks to their excellent biocompatibility, easy-to-modify surface, adjustable particle size, and remarkable immuno-enhancing activity. However, the application of MSNs is still greatly limited by some severe challenges including the unclear and complicated relationships of structure and immune effect. Herein, three commonly used MSNs with different skeletons including MSN with tetrasulfide bonds (TMSN), MSN containing ethoxy framework (EMSN), and pure -Si-O-Si- framework of MSN (MSN) are comprehensively compared to study the impact of chemical construction on immune effect. The results fully demonstrate that the three MSNs have great promise in improving cellular immunity for tumor immunotherapy. Moreover, the TMSN performs better than the other two MSNs in antigen loading, cellular uptake, reactive oxygen species (ROS) generation, lymph node targeting, immune activation, and therapeutic efficiency. The findings provide a new paradigm for revealing the structure-function relationship of mesoporous silica nanoadjuvants, paving the way for their future clinical application.

Effector CD4+ T-cell subsets in Takayasu arteritis-differences between the peripheral blood and the aorta.

Takayasu arteritis (TAK) is a granulomatous vasculitis that affects large arteries. T cells are important in TAK pathophysiology as these cells orchestrate granulomatous infiltration in arteries. This study aims to evaluate effector CD4+ T cells in the peripheral blood and the aortic wall of TAK patients and to analyze associations with disease activity and therapy. We performed a longitudinal study including 30 TAK patients and 30 controls. CD3+ T cells, CD3+CD4- T cells, CD4+ T cells, and Th1, Th2, and Th17 cells were evaluated in peripheral blood by flow cytometry, and the expression of CD4, CD8, Tbet, GATA-3, and RORγT was analyzed in the aorta of six patients by immunohistochemistry. TAK patients presented lower CD3+ T cells and CD4+ T cells (P = 0.031 and P = 0.039, respectively) than controls. Patients with active disease and those in remission had higher proportions of Th17 cells than controls (P = 0.016 and P = 0.004, respectively). Therapy for TAK did not result in significant differences concerning CD4+ effector T-cell subpopulations. Disease duration correlated with the number and percentage of Th2 cells (rho = -0.610 and rho = -0.463, respectively) and with Th17 cells (rho = -0.365 and rho = -0.568). In the aorta, the expression of CD8 was higher than CD4, whereas GATA-3, Tbet, and RORγT were expressed in this order of frequency. In conclusion, TAK patients present an increased Th17 response in the peripheral blood regardless of disease activity, whereas in the aortic tissue CD8 cells and the Th2 response were predominant.

Cellular immune response to the anti-SARS-CoV-2 BNT162b2 mRNA vaccine in pediatric autoimmune inflammatory rheumatic disease patients and controls.

This paper aims to compare the cellular immune response to the SARS-CoV-2 BNT162b2 vaccine of pediatric patients with autoimmune inflammatory rheumatic disease (pAIIRD) and healthy controls. A prospective longitudinal study was conducted between April 2021 and December 2022 at the Tel Aviv Medical Center. Children <18 years, with pediatric-onset AIIRD and healthy controls, who have received at least two doses of the BNT162b2 vaccine, were included. Humoral response was evaluated by serum levels of anti-SARS-CoV-2 receptor-binding domain antibodies. Cellular response was evaluated by flow cytometry, measuring IFNγ and TNFα production by CD4+ T cells following stimulation with SARS-CoV-2 Spike peptide mix. The study included 20 pAIIRD patients and 11 controls. The mean age of participants was 12.6 ±â€…2.94 years, with 58.1% females. The cellular response to the BNT162b2 vaccine was statistically similar in both groups. However, the humoral response was statistically lower in pAIIRD compared with the healthy control group. There was no statistically significant correlation between the humoral response and cellular response. During the study period, 43.75% of AIIRD children and 72.7% of controls had a breakthrough COVID-19 infection (P = 0.48). Bivariate models examining the effect of the cellular response and presence of an AIIRD on breakthrough infections found no effect. Compared with healthy controls, pAIIRD demonstrated similar cellular responses. Patients showed reduced humoral response compared with healthy adolescents, but similar breakthrough infection rates. These findings may support the importance of the cellular response in protecting against COVID-19 infections.

Mature beyond their years: young children who escape detection of parasitemia despite living in settings of intense malaria transmission.

Despite having the highest risk of progressing to severe disease due to lack of acquired immunity, the youngest children living in areas of highly intense malaria transmission have long been observed to be infected at lower rates than older children. Whether this observation is due to reduced exposure to infectious mosquito bites from behavioral and biological factors, maternally transferred immunity, genetic factors, or enhanced innate immunity in the young child has intrigued malaria researchers for over half a century. Recent evidence suggests that maternally transferred immunity may be limited to early infancy and that the young child's own immune system may contribute to control of malarial symptoms early in life and prior to the development of more effective adaptive immunity. Prospective studies of active and passive detection of Plasmodium falciparum blood-stage infections have identified young children (<5 years old) who remain uninfected through a defined surveillance period despite living in settings of highly intense malaria transmission. Yet, little is known about the potential immunological basis for this 'aparasitemic' phenotype. In this review, we summarize the observational evidence for this phenotype in field studies and examine potential reasons why these children escape detection of parasitemia, covering factors that are either extrinsic or intrinsic to their developing immune system. We discuss the challenges of distinguishing malaria protection from lack of malaria exposure in field studies. We also identify gaps in our knowledge regarding cellular immunity in the youngest age group and propose directions that researchers may take to address these gaps.

Evaluation of vaccine candidates against Rhodococcus equi in BALB/c mice infection model: cellular and humoral immune responses.

Rhodococcus equi (R. equi) is a zoonotic opportunistic pathogen that mainly causes fatal lung and extrapulmonary abscesses in foals and immunocompromised individuals. To date, no commercial vaccine against R. equi exists. We previously screened all potential vaccine candidates from the complete genome of R. equi using a reverse vaccinology approach. Five of these candidates, namely ABC transporter substrate-binding protein (ABC transporter), penicillin-binding protein 2 (PBD2), NlpC/P60 family protein (NlpC/P60), esterase family protein (Esterase), and M23 family metallopeptidase (M23) were selected for the evaluation of immunogenicity and immunoprotective effects in BALB/c mice model challenged with R. equi. The results showed that all five vaccine candidate-immunized mice experienced a significant increase in spleen antigen-specific IFN-γ- and TNF-α-positive CD4 + and CD8 + T lymphocytes and generated robust Th1- and Th2-type immune responses and antibody responses. Two weeks after the R. equi challenge, immunization with the five vaccine candidates reduced the bacterial load in the lungs and improved the pathological damage to the lungs and livers compared with those in the control group. NlpC/P60, Esterase, and M23 were more effective than the ABC transporter and PBD2 in inducing protective immunity against R. equi challenge in mice. In addition, these vaccine candidates have the potential to induce T lymphocyte memory immune responses in mice. In summary, these antigens are effective candidates for the development of protective vaccines against R. equi. The R. equi antigen library has been expanded and provides new ideas for the development of multivalent vaccines.

The role of PB1-F2 in adaptation of high pathogenicity avian influenza virus H7N7 in chickens.

Avian influenza viruses (AIV) of the H7N7 subtype are enzootic in the wild bird reservoir in Europe, cause infections in poultry, and have sporadically infected humans. The non-structural protein PB1-F2 is encoded in a second open frame in the polymerase segment PB1 and its sequence varies with the host of origin. While mammalian isolates predominantly carry truncated forms, avian isolates typically express full-length PB1-F2. PB1-F2 is a virulence factor of influenza viruses in mammals. It modulates the host immune response, causing immunopathology and increases pro-inflammatory responses. The role of full-length PB1-F2 in IAV pathogenesis as well as its impact on virus adaptation and virulence in poultry remains enigmatic. Here, we characterised recombinant high pathogenicity AIV (HPAIV) H7N7 expressing or lacking PB1-F2 in vitro and in vivo in chickens. In vitro, full-length PB1-F2 modulated viability of infected chicken fibroblasts by limiting apoptosis. In chickens, PB1-F2 promoted gastrointestinal tropism, as demonstrated by enhanced viral replication in the gut and increased cloacal shedding. PB1-F2's effects on cellular immunity however were marginal. Overall, chickens infected with full-length PB1-F2 virus survived for shorter periods, indicating that PB1-F2 is also a virulence factor in bird-adapted viruses.

A bacterial ghost vaccine against Aeromonas salmonicida infection in turbot (Scophthalmus maximus).

Aeromonas salmonicida is one of the most prevalent pathogens that causes huge economic losses to aquaculture. Effective vaccination is the first choice for preventing infection. Bacterial ghost (BG), an empty bacterial shell devoid of cytoplasm, is a promising vaccine antigen with distinct advantages. Herein, we established strategies for producing a substantial yield of A. salmonicida ghost (ASG) and investigated the immune-protective properties of it. As a result, 2.84 mg/ml NaOH was discovered to be capable of inducing considerable amounts of ASG. Furthermore, the ASG vaccine elicited adaptive immunity in turbots after rapid activation of innate immunity. Even though formalin-killed cells (FKC) produced a few more antibodies than ASG, ASG ultimately provided a much stronger immune protection effect because it strengthened cellular immunity, with a relative percentage survival (RPS) of 50.1 % compared to FKC. These findings demonstrated that ASG effectively activated cell-mediated immunity, which helped get rid of microorganisms inside cells. Therefore, this study presented novel perspectives for future research on furunculosis vaccine products based on ASG as an antigen.

The role of acquired host immunity in periodontal diseases.

The aim of this narrative review is to relate the contribution of European researchers to the complex topic of the host immune system in periodontal disease, focusing on acquired immunity. Other chapters in this volume will address the genetics and autoantibody responses and other forms of immunity to periodontal disease. While the contribution of European authors is the focus, global literature is included in this descriptive narrative for contextual clarity, albeit many with European co-authors. The topic is relatively intense and is thus broken down into sections outlined below, tackled as descriptive narratives to enhance understanding. Any attempt at a systematic or scoping review was quickly abandoned given the descriptive nature and marked variation of approach in almost all publications. Even the most uniform area of this acquired periodontal immunology literature, antibody responses to putative pathogens in periodontal diseases, falls short of common structures and common primary outcome variables one would need and expect in clinical studies, where randomized controlled clinical trials (RCTs) abound. Addressing 'the host's role' in immunity immediately requires a discussion of host susceptibility, which necessitates consideration of genetic studies (covered elsewhere in the volume and superficially covered here).

Measles Infection Dose Responses: Insights from Mathematical Modeling.

How viral infections develop can change based on the number of viruses initially entering the body. The understanding of the impacts of infection doses remains incomplete, in part due to challenging constraints, and a lack of research. Gaining more insights is crucial regarding the measles virus (MV). The higher the MV infection dose, the earlier the peak of acute viremia, but the magnitude of the peak viremia remains almost constant. Measles is highly contagious, causes immunosuppression such as lymphopenia, and contributes substantially to childhood morbidity and mortality. This work investigated mechanisms underlying the observed wild-type measles infection dose responses in cynomolgus monkeys. We fitted longitudinal data on viremia using maximum likelihood estimation, and used the Akaike Information Criterion (AIC) to evaluate relevant biological hypotheses and their respective model parameterizations. The lowest AIC indicates a linear relationship between the infection dose, the initial viral load, and the initial number of activated MV-specific T cells. Early peak viremia is associated with high initial number of activated MV-specific T cells. Thus, when MV infection dose increases, the initial viremia and associated immune cell stimulation increase, and reduce the time it takes for T cell killing to be sufficient, thereby allowing dose-independent peaks for viremia, MV-specific T cells, and lymphocyte depletion. Together, these results suggest that the development of measles depends on virus-host interactions at the start and the efficiency of viral control by cellular immunity. These relationships are additional motivations for prevention, vaccination, and early treatment for measles.

Caveats of chimpanzee ChAdOx1 adenovirus-vectored vaccines to boost anti-SARS-CoV-2 protective immunity in mice.

Several COVID-19 vaccines use adenovirus vectors to deliver the SARS-CoV-2 spike (S) protein. Immunization with these vaccines promotes immunity against the S protein, but against also the adenovirus itself. This could interfere with the entry of the vaccine into the cell, reducing its efficacy. Herein, we evaluate the efficiency of an adenovirus-vectored vaccine (chimpanzee ChAdOx1 adenovirus, AZD1222) in boosting the specific immunity compared to that induced by a recombinant receptor-binding domain (RBD)-based vaccine without viral vector. Mice immunized with the AZD1222 human vaccine were given a booster 6 months later, with either the homologous vaccine or a recombinant vaccine based on RBD of the delta variant, which was prevalent at the start of this study. A significant increase in anti-RBD antibody levels was observed in rRBD-boosted mice (31-61%) compared to those receiving two doses of AZD1222 (0%). Significantly higher rates of PepMix™- or RBD-elicited proliferation were also observed in IFNγ-producing CD4 and CD8 cells from mice boosted with one or two doses of RBD, respectively. The lower efficiency of the ChAdOx1-S vaccine in boosting specific immunity could be the result of a pre-existing anti-vector immunity, induced by increased levels of anti-adenovirus antibodies found both in mice and humans. Taken together, these results point to the importance of avoiding the recurrent use of the same adenovirus vector in individuals with immunity and memory against them. It also illustrates the disadvantages of ChAdOx1 adenovirus-vectored vaccine with respect to recombinant protein vaccines, which can be used without restriction in vaccine-booster programs. KEY POINTS: • ChAdOx1 adenovirus vaccine (AZD1222) may not be effective in boosting anti-SARS-CoV-2 immunity • A recombinant RBD protein vaccine is effective in boosting anti-SARS-CoV-2 immunity in mice • Antibodies elicited by the rRBD-delta vaccine persisted for up to 3 months in mice.

Construction of lymph nodes-targeting tumor vaccines by using the principle of DNA base complementary pairing to enhance anti-tumor cellular immune response.

Tumor vaccines, a crucial immunotherapy, have gained growing interest because of their unique capability to initiate precise anti-tumor immune responses and establish enduring immune memory. Injected tumor vaccines passively diffuse to the adjacent draining lymph nodes, where the residing antigen-presenting cells capture and present tumor antigens to T cells. This process represents the initial phase of the immune response to the tumor vaccines and constitutes a pivotal determinant of their effectiveness. Nevertheless, the granularity paradox, arising from the different requirements between the passive targeting delivery of tumor vaccines to lymph nodes and the uptake by antigen-presenting cells, diminishes the efficacy of lymph node-targeting tumor vaccines. This study addressed this challenge by employing a vaccine formulation with a tunable, controlled particle size. Manganese dioxide (MnO2) nanoparticles were synthesized, loaded with ovalbumin (OVA), and modified with A50 or T20 DNA single strands to obtain MnO2/OVA/A50 and MnO2/OVA/T20, respectively. Administering the vaccines sequentially, upon reaching the lymph nodes, the two vaccines converge and simultaneously aggregate into MnO2/OVA/A50-T20 particles through base pairing. This process enhances both vaccine uptake and antigen delivery. In vitro and in vivo studies demonstrated that, the combined vaccine, comprising MnO2/OVA/A50 and MnO2/OVA/T20, exhibited robust immunization effects and remarkable anti-tumor efficacy in the melanoma animal models. The strategy of controlling tumor vaccine size and consequently improving tumor antigen presentation efficiency and vaccine efficacy via the DNA base-pairing principle, provides novel concepts for the development of efficient tumor vaccines.

Humoral and Cellular Immune Response to SARS-CoV-2 S and N Proteins.

The pandemic of a new coronavirus infection that has lasted for more than 3 years, is still accompanied by frequent mutations in the S protein of SARS-CoV-2 and emergence of new virus variants causing new disease outbreak. Of all coronaviral proteins, the S and N proteins are the most immunogenic. The aim of this study was to compare the features of the humoral and T-cell immune responses to the SARS-CoV-2 S and N proteins in people with different histories of interaction with this virus. The study included 27 individuals who had COVID-19 once, 23 people who were vaccinated twice with the Sputnik V vaccine and did not have COVID-19, 22 people who had COVID-19 and were vaccinated twice with Sputnik V 6-12 months after the disease, and 25 people who had COVID-19 twice. The level of antibodies was determined by the enzyme immunoassay, and the cellular immunity was assessed by the expression of CD107a on CD8high lymphocytes after recognition of SARS-CoV-2 antigens. It was shown that the humoral immune response to the N protein was formed mainly by short-lived plasma cells synthesizing IgG antibodies of all four subclasses with a gradual switch from IgG3 to IgG1. The response to the S protein was formed by short-lived plasma cells at the beginning of the response (IgG1 and IgG3 subclasses) and then by long-lived plasma cells (IgG1 subclass). The dynamics of antibody level synthesized by the short-lived plasma cells was described by the Fisher equation, while changes in the level of antibodies synthesized by the long-lived plasma cells were described by the Erlang equation. The level of antibodies in the groups with the hybrid immunity exceeded that in the group with the post-vaccination immunity; the highest antibody content was observed in the group with the breakthrough immunity. The cellular immunity to the S and N proteins differed depending on the mode of immune response induction (vaccination or disease). Importantly, the response of heterologous CD8+ T cell to the N proteins of other coronaviruses may be involved in the immune defense against SARS-CoV-2.

Effects of the induction of humoral and cellular immunity by third vaccination for SARS-CoV-2.

INTRODUCTION: To control the spread of severe disease caused by mutant strains of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), it is necessary to determine whether continued vaccination enhances humoral and cellular immunity. AIM: In this study, we examined the changes in humoral and cellular immunity to SARS-CoV-2 after administration of the third vaccination in Japanese adults who had received the second dose of messenger ribonucleic acid (mRNA)-1273 vaccine and the third vaccination (BNT162b2 or mRNA-1273). METHODS: We measured anti-spike antibodies in immunoglobulin G (IgG) and anti-nucleocapsid IgG titers in the serum of the vaccinated subjects. To evaluate cellular immunity, the peripheral blood mononuclear cells of inoculated individuals were cultured with spiked proteins, including those of the SARS-CoV-2 conventional strain and Omicron strain, and then subjected to enzyme-linked immunospot (ELISPOT). RESULTS: The results revealed that the anti-SARS-CoV-2 spike protein antibody titer increased after the third vaccination and was maintained; however, a decrease was observed at 6 months after vaccination. SARS-CoV-2 antigen-specific T helper (Th)1 and Th2 cell responses were also induced after the third vaccination and were maintained for 6 months after vaccination. Furthermore, induction of cellular immunity against Omicron strains by the omicron non-compliant vaccines, BNT162b2 or mRNA-1273, was observed. CONCLUSION: These findings demonstrate the effectiveness of vaccination against unknown mutant strains that may occur in the future and provide important insights into vaccination strategies.