Development Of Vaccination Strategies Research Articles

Prediction of influenza outbreaks in Fuzhou, China: comparative analysis of forecasting models

BackgroundInfluenza is a highly contagious respiratory disease that presents a significant challenge to public health globally. Therefore, effective influenza prediction and prevention are crucial for the timely allocation of resources, the development of vaccine strategies, and the implementation of targeted public health interventions.MethodIn this study, we utilized historical influenza case data from January 2013 to December 2021 in Fuzhou to develop four regression prediction models: SARIMA, Prophet, Holt-Winters, and XGBoost models. Their predicted performance was assessed by using influenza data from the period from January 2022 to December 2022 in Fuzhou. These models were used for fitting and prediction analysis. The evaluation metrics, including Mean Squared Error (MSE), Root Mean Squared Error (RMSE), and Mean Absolute Error (MAE), were employed to compare the performance of these models.ResultsThe results indicate that the epidemic of influenza in Fuzhou exhibits a distinct seasonal and cyclical pattern. The influenza cases data displayed a noticeable upward trend and significant fluctuations. In our study, we employed SARIMA, Prophet, Holt-Winters, and XGBoost models to predict influenza outbreaks in Fuzhou. Among these models, the XGBoost model demonstrated the best performance on both the training and test sets, yielding the lowest values for MSE, RMSE, and MAE among the four models.ConclusionThe utilization of the XGBoost model significantly enhances the prediction accuracy of influenza in Fuzhou. This study makes a valuable contribution to the field of influenza prediction and provides substantial support for future influenza response efforts.

Accelerate vaccine development using seamless phase 2/3 trial designs

ABSTRACT Background Traditional vaccine development, often a lengthy and costly process of three separated phases. However, the swift development of COVID-19 vaccines highlighted the critical importance of accelerating the approval of vaccines. This article showcases a seamless phase 2/3 trial design to expedite the development process, particularly for multi-valent vaccines. Research Design and Methods This study utilizes simulation to compare the performance of seamless phase 2/3 design with that of conventional trial design, specifically by re-envisioning a 9-valent HPV vaccine trial. Across three cases, several key performance metrics are evaluated: overall power, type I error rate, average sample size, trial duration, the percentage of early stop, and the accuracy of dose selection. Results On average, when the experimental vaccine was assumed to be effective, the seamless design that performed interim analyses based solely on efficacy saved 555.73 subjects, shortened trials by 10.29 months, and increased power by 3.70%. When the experimental vaccine was less effective than control, it saved an average of 887.73 subjects while maintaining the type I error rate below 0.025. Conclusion The seamless design proves to be a compelling strategy for vaccine development, given its versatility in early stopping, re-estimating sample sizes, and shortening trial durations.

Current Strategies for Vaccine Prophylaxis of Lyme Disease

Relevance. Lyme disease (LD) remains an important public health problem, especially in Russia, where the incidence is consistently high. To date, there is still no available vaccine against LD, and prevention involves non-specific measures. Aim: to review the literature and summarise data on progress, approaches and strategies for LD vaccine development. Conclusions. The first LD vaccines were developed in the 1990s. An OspA-based vaccine (LYMErix) was commercially available in the early 2000s but not widely distributed. An important milestone in the development of LD vaccines was the shift from the development of monovalent vaccines based on a single type of outer surface protein to the development of multivalent combinations that provide protection against different Borrelia genospecies. A multivalent OspA-based vaccine (VLA15) is in phase III clinical trials and is likely to be the next LD vaccine available on the market. New genetic strategies for vaccine development, identification of new immunogens, and development of vaccines targeting different parts of the LD transmission cycle are of broad interest for further development of LD vaccines.

Update on feline calicivirus: viral evolution, pathogenesis, epidemiology, prevention and control.

Feline calicivirus (FCV) is a prevalent and impactful viral pathogen affecting domestic cats. As an RNA virus, FCV exhibits high mutability and genetic plasticity, enabling its persistence within cat populations. Viral genetic diversity is associated with a broad spectrum of clinical manifestations, ranging from asymptomatic infections and mild oral and upper respiratory tract diseases to the potential development of virulent systemic, and even fatal conditions. This diversity poses distinctive challenges in diagnosis, treatment, and prevention of diseases caused by FCV. Over the past four decades, research has significantly deepened understanding of this pathogen, with an emphasis on molecular biology, evolutionary dynamics, vaccine development, and disease management strategies. This review discusses various facets of FCV, including its genomic structure, evolution, innate immunity, pathogenesis, epidemiology, and approaches to disease management. FCV remains a complex and evolving concern in feline health, requiring continuous research to enhance understanding of its genetic diversity, to improve vaccine efficacy, and to explore novel treatment options.

Proteome profile of Leishmania donovani Centrin1−/− parasite-infected human macrophage cell line and its implications in determining possible mechanisms of protective immunity

Our developed cell division-specific ‘centrin’ gene deleted Leishmania donovani (LdCen1−/−) the causative parasite of the fatal visceral-leishmaniasis (VL), exhibits a selective growth arrest at the intracellular stage and is anticipated as a live attenuated vaccine candidate against VL. LdCen1−/− immunization in animals has shown increased IFN-γ secreting CD4+ and CD8+ T cells along with protection conferred by a protective proinflammatory immune response. A label-free proteomics approach has been employed to understand the physiology of infection and predict disease interceptors during Leishmania-host interactions. Proteomic modulation after infection of human macrophage cell lines suggested elevated annexin A6, implying involvement in various biological processes such as membrane repair, transport, actin dynamics, cell proliferation, survival, differentiation, and inflammation, thereby potentiating its immunological protective capacity. Additionally, S100A8 and S100A9 proteins, known for maintaining homeostatic balance in regulating the inflammatory response, have been upregulated after infection. The inhibitory clade of serpins, known to inhibit cysteine proteases (CPs), was upregulated in host cells after 48 h of infection. This is reflected in the diminished expression of CPs in the parasites during infection. Such proteome analysis confirms LdCen1−/− efficacy as a vaccine candidate and predicts potential markers in future vaccine development strategies against infectious diseases.

Promoting Fair Vaccination Strategies through Influence Maximization: A Case Study on COVID-19 Spread

The aftermath of the Covid-19 pandemic saw more severe outcomes for racial minority groups and economically-deprived communities. Such disparities can be explained by several factors, including unequal access to healthcare, as well as the inability of low income groups to reduce their mobility due to work or social obligations. Moreover, senior citizens were found to be more susceptible to severe symptoms, largely due to age-related health reasons. Adapting vaccine distribution strategies to consider a range of demographics is therefore essential to address these disparities. In this study, we propose a novel approach that utilizes influence maximization (IM) on mobility networks to develop vaccination strategies which incorporate demographic fairness. By considering factors such as race, social status, age, and associated risk factors, we aim to optimize vaccine distribution to achieve various fairness definitions for one or more protected attributes at a time. Through extensive experiments conducted on Covid-19 spread in three major metropolitan areas across the United States, we demonstrate the effectiveness of our proposed approach in reducing disease transmission and promoting fairness in vaccination distribution.

The hapten rigidity improves antibody performances in immunoassay for rifamycins: Immunovalidation and molecular mechanism

The immunogenicity of haptens determines the performance of the resultant antibody for small molecules. Rigidity is one of the basic physicochemical properties of haptens. However, few studies have investigated the effect of hapten rigidity on the strength of an immune response and overall antibody performance. Herein, we introduce three molecular descriptors that quantify hapten rigidity. By using of these descriptors, four rifamycin haptens with varied rigidity were designed. The structural and physicochemical feasibility of the designed haptens was then assessed by computational chemistry. Immunization demonstrated that the strength of induced immune responses, i.e., the titer and affinity of antiserum, was significantly increased with increased rigidity of haptens. Furthermore, molecular dynamic simulations demonstrated conformation constraint of rigid haptens contributed to the initial binding and activation of naïve B cells. Finally, a highly sensitive indirect competitive enzyme-linked immunosorbent assay was developed for detection of rifaximin, with an IC50 of 1.1 μg/L in buffer and a limit of detection of 0.2–11.3 μg/L in raw milk, river water, and soil samples. This work provides new insights into the effect of hapten rigidity on immunogenicity and offers new hapten design strategies for antibody discovery and vaccine development of small molecules.

Self-assembled ferritin-based nanoparticles elicit a robust broad-spectrum protective immune response against SARS-CoV-2 variants

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its variants has resulted in global economic losses and posed a threat to human health. The pandemic highlights the urgent need for an efficient, easily producible, and broad-spectrum vaccine. Here, we present a potentially universal strategy for the rapid and general design of vaccines, focusing on the design and testing of omicron BA.5 RBD-conjugated self-assembling ferritin nanoparticles (NPs). The covalent bonding of RBD-Fc to protein A-ferritin was easily accomplished through incubation, resulting in fully multivalent RBD-conjugated NPs that exhibited high structural uniformity, stability, and efficient assembly. The ferritin nanoparticle vaccine synergistically stimulated the innate immune response, Tfh-GCB-plasma cell-mediated activation of humoral immunity and IFN-γ-driven cellular immunity. This nanoparticle vaccine induced a high level of cross-neutralizing responses and protected golden hamsters challenged with multiple mutant strains from infection-induced clinical disease, providing a promising strategy for broad-spectrum vaccine development for SARS-CoV-2 prophylaxis. In conclusion, the nanoparticle conjugation platform holds promise for its potential universality and competitive immunization efficacy and is expected to facilitate the rapid manufacturing and broad application of next-generation vaccines.

Ferritin-binding and ubiquitination-modified mRNA vaccines induce potent immune responses and protective efficacy against SARS-CoV-2

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) incessantly engenders mutating strains via immune escape mechanisms, substantially escalating the risk of severe acute respiratory syndrome. In this context, the urgent development of innovative and efficacious mRNA vaccines is imperative. In our study, we synthesized six unique mRNA vaccine formulations: the Receptor Binding Domain (RBD) monomer vaccine, RBD dimer (2RBD) vaccine, RBD-Ferritin (RBD-Fe) vaccine, ubiquitin-modified wild-type Nucleocapsid gene (WT-N) vaccine, rearranged Nucleocapsid gene (Re-N) vaccine, and an epitope-based (COVID-19 epitope) vaccine, all encapsulated within the lipid nanoparticle SM102. Immunization studies conducted on C57BL/6 mice with these vaccines revealed that the RBD monomer, RBD dimer (2RBD), and RBD-Fe vaccines elicited robust titers of specific antibodies, including neutralizing antibodies. In contrast, the wild-type N gene (WT-N), rearrange N gene (Re-N), and COVID-19 epitope vaccines predominantly induced potent cellular immune responses. Protective efficacy assays in golden hamsters demonstrated that vaccinated cohorts showed significant reduction in lung pathology, markedly lower viral loads in the lungs, nasal turbinates, and trachea, and substantially reduced transcriptional and expression levels of pro-inflammatory cytokines. Overall, our vaccine candidates pave the way for novel strategies in vaccine development against various infectious agents and establish a critical foundation for the formulation of advanced vaccines targeting emerging pathogens.

In silico Designing of a Multi-epitope-based Subunit Vaccine against SARS-CoV-2 (Delta Variant) by Exploiting Its Structural Proteins: A Reverse Vaccinomics and Immunoinformatics Approach

Background: The continuously emerging novel strains of SARS-CoV-2 remain a menace to the global population. The vicious delta variant (originated in India) is considered one of the most infectious/contagious variants of SARS-CoV-2. The transmission frequency of this variant is 225% higher than other variants, extending its prevalence and causing a massive surge in the COVID-19 pandemic. It is also the most ravenous variant among others. Objective: Though the delta variant has already disappeared, it could re-emerge/come out at any time with a more powerful strike than earlier. Therefore, to tackle such ferocity, this research is undertaken with a next-generation vaccine development strategy to design a multi-epitope-based subunit vaccine against the delta variant of SARS-CoV-2, which might boost the body's immunity. Materials and Methods: In the present investigation, reverse vaccinomics and immunoinformatics approaches were adopted to create an immune-stimulating prospective vaccine candidate having B cell, helper T cell (Th)/helper T lymphocyte (HTL), cytotoxic T cell (Tc)/cytotoxic T lymphocyte (CTL), and interferon-gamma (IFN-γ) inducing epitopes by exploiting the SARS-CoV-2 (delta variant) (GenBank: MZ724536.1) structural proteins: envelope glycoprotein (E), nucleocapsid phosphoprotein (N), surface glycoprotein (S), and membrane glycoprotein (M). The established vaccine construct was then completed by combining antigenic epitopes with adjuvants and linkers. Subsequently, the 3D model of the suggested vaccine was created and docked with an immune receptor (Toll-Like Receptor-4). A molecular dynamics (MD) simulation study was performed to confirm the binding stability between the vaccine conjugate and TLR4. Later, an immune simulation study was carried out to predict the in silico immune response of the vaccine candidate. To effectively express the developed vaccine in a bacterial system (E. coli), in silico codon optimization and cloning were done in an expression vector to manufacture it on a large scale. Results: According to the computational analysis, the vaccine candidate was found to be highly antigenic while maintaining favorable properties for the human body. Molecular docking and dynamics simulation study between the suggested vaccine construct and TLR4 immune receptor depicted it as extremely efficient and stable, ensuring a proper immunological response within the host cell. Eventually, an in silico immune simulation study of the vaccine candidate demonstrated a robust immune response to vaccine administration. Conclusion: We have hypothesized that the constructed vaccine model is benign, stable, and immunogenic, making it a promising/potent candidate for immune system stimulation against SARSCOV- 2 (DV). Hereof, wet lab-based investigations are needed to justify the competence of the novel vaccine candidate towards the delta variant along with other variants of SARS-CoV-2.

Genomic Landscape of Lynch Syndrome Colorectal Neoplasia Identifies Shared Mutated Neoantigens for Immunoprevention

Background & AimsLynch syndrome (LS) carriers develop mismatch repair deficient (MMRd) neoplasia with high neoantigen (neoAg) rates. No detailed information on targetable neoAgs from LS pre-cancers exists, which is crucial for vaccine development and immune-interception strategies. We report a focused somatic mutation and frameshift-neoAg landscape of microsatellite loci from colorectal polyps without malignant potential (PWOMPs), pre-cancers and early-stage cancers in LS carriers. MethodsWe generated paired whole-exome and transcriptomic sequencing data from 8 colorectal PWOMPs, 41 pre-cancers, 8 advanced pre-cancers, and 12 early-stage cancers of 43 LS carriers. A computational pipeline was developed to predict, rank, and prioritize the top 100 detected mutated neoAgs that were validated in vitro using ELISpot and tetramer assays. ResultsMutation calling revealed >10 mut/Mb in 83% of cancers, 63% of advanced pre-cancers, and 20% of pre-cancers. Cancers displayed an average of 616 MHC-I neoAgs/sample, 294 in advanced pre-cancers, and 107 in pre-cancers. No neoAgs were detected in PWOMPs. A total of 65% of our top 100 predicted neoAgs were immunogenic in vitro, and were present in 92% of cancers, 50% of advanced pre-cancers, and 29% of pre-cancers. We observed increased levels of naïve CD8+ and memory CD4+ T-cells in MMRd cancers and pre-cancers via transcriptomics analysis. ConclusionsShared frameshift-neoAgs are generated within unstable microsatellite loci at initial stages of LS carcinogenesis and can induce T-cell responses, generating opportunities for vaccine development, targeting LS pre-cancers and early-stage cancers.

Original Research: Predictors of COVID-19 Vaccine Hesitancy Among Asian Indians in the United States: A Cross-Sectional Descriptive Study.

Although COVID-19 is a highly infectious disease, vaccine hesitancy remains a primary barrier to attaining full population inoculation. Numerous factors related to vaccine hesitancy have been identified. The aim of this study was to explore associations between select demographic variables and COVID-19 vaccine hesitancy among Asian Indians in the United States. The study used a cross-sectional, descriptive, correlational design. The sample consisted of 363 Asian Indians living in the United States who were 18 years of age or older and were literate in English. Vaccine hesitancy was assessed using an online survey. Both descriptive and inferential statistical analyses were conducted. Inferential tests included t tests, regression analyses, and analysis of variance (ANOVA) tests. As participant age increased, there was a statistically significant proportionate increase in the total vaccine hesitancy score ( P = 0.01). There were also statistically significant differences in the vaccine hesitancy scores of participants with no more than a high school degree compared to those with associate or bachelor's degrees, although this finding was based on just six participants. Although most participants had already been vaccinated, many identified reasons for feeling some degree of vaccine hesitancy. The reasons for vaccine hesitancy vary by individual and are often complex. The results of this study will help guide public health agencies and health care personnel in developing vaccination strategies tailored to the specific requirements of Asian Indians in the United States, which could reduce vaccine hesitancy in this population.

Relative effectiveness and durability of booster doses of SARS-CoV-2 vaccines: A systematic review and meta-analysis

<p>Billions of people worldwide have received booster doses of SARS-CoV-2 vaccines. Continuous monitoring of the relative vaccine effectiveness (rVE) and durability of booster vaccination over previous vaccinations is important for developing vaccination strategies during the post-pandemic era. We conducted a systematic review and meta-analysis of trials and observational studies to determine the rVE of the 1<sup>st</sup> booster over no booster and that of the 2<sup>nd</sup> booster over the 1<sup>st</sup> booster. Three trials and 91 observational studies were included in this systematic review. For the 1<sup>st</sup> booster homologous vaccination, the rVE at a median of 9 weeks after booster vaccination was 66.9% (95% confidence interval: 59.8%, 72.7%), 75.9% (62.6%, 84.5%), 74.1% (66.9%, 79.8%), 86.1% (78.7%, 90.9%) and 84.2% (78.3%, 88.5%) against overall infection, symptomatic infection, hospital admission, severe infection and COVID-19-related death, respectively. The rVE against overall infection was affected by variants of concern and vaccine types and waned by average of 4.3% (3.3%, 5.4%; <i>P-trend</i><0.01) per week. Heterologous regimens for the 1<sup>st</sup> booster vaccination demonstrated effectiveness comparable to that of homologous regimens. The rVE of the 2<sup>nd</sup> booster homologous vaccination at a median of 7 weeks after booster vaccination was 41.9% (31.2%, 51.0%), 53.1% (24.5%, 70.9%), 60.6% (55.3%, 65.3%), 56.4% (45.3%, 65.2%) and 68.2% (51.2%, 79.2%) against the five outcomes above, respectively, with no significant decrease in the rVE of 2<sup>nd</sup> booster vaccination. In conclusion, both the 1<sup>st</sup> and 2<sup>nd</sup> booster homologous vaccinations provided additional protection against mild and severe infections. The rVE of the 1<sup>st</sup> booster rapidly waned over time. The rVE of the 2<sup>nd</sup> booster, including heterologous vaccination, its durability and the sources of heterogeneity, however, remains uncertain and more relevant studies are needed.</p>

Neutron Scattering Analysis of Cryptococcus neoformans Polysaccharide Reveals Solution Rigidity and Repeating Fractal-like Structural Patterns.

Cryptococcus neoformans is a fungal pathogen that can cause life-threatening brain infections in immunocompromised individuals. Unlike other fungal pathogens, it possesses a protective polysaccharide capsule that is crucial for its virulence. During infections, Cryptococcus cells release copious amounts of extracellular polysaccharides (exo-PS) that interfere with host immune responses. Both exo-PS and capsular-PS play pivotal roles in Cryptococcus infections and serve as essential targets for disease diagnosis and vaccine development strategies. However, understanding their structure is complicated by their polydispersity, complexity, sensitivity to sample isolation and processing, and scarcity of methods capable of isolating and analyzing them while preserving their native structure. In this study, we employ small-angle neutron scattering (SANS) and ultra-small-angle neutron scattering (USANS) for the first time to investigate both fungal cell suspensions and extracellular polysaccharides in solution. Our data suggests that exo-PS in solution exhibits collapsed chain-like behavior and demonstrates mass fractal properties that indicate a relatively condensed pore structure in aqueous environments. This observation is also supported by scanning electron microscopy (SEM). The local structure of the polysaccharide is characterized as a rigid rod, with a length scale corresponding to 3-4 repeating units. This research not only unveils insights into exo-PS and capsular-PS structures but also demonstrates the potential of USANS for studying changes in cell dimensions and the promise of contrast variation in future neutron scattering studies.

Efficient formation and maintenance of humoral and CD4 T-cell immunity targeting the viral capsid in acute-resolving hepatitis E infection

CD4 T cells shape the neutralizing antibody (nAb) response and facilitate viral clearance in various infections. Knowledge of their phenotype, specificity and dynamics in hepatitis E virus (HEV) infection is limited. HEV is enterically transmitted as a naked virus (nHEV) but acquires a host-derived quasi-envelope (eHEV) when budding from cells. While nHEV is composed of the open reading frame (ORF)-2-derived capsid, eHEV particles also contain ORF3-derived proteins. We aimed to longitudinally characterize the HEV-specific CD4 T cells targeting ORF1, 2 and 3 and antibodies against nHEV or eHEV in immunocompetent individuals with acute and resolved HEV infection. HEV-specific CD4 T cells were analyzed by intracellular cytokine staining after stimulation with in silico-predicted ORF1- and ORF2-derived epitopes and overlapping peptides spanning the ORF3 region. Exvivo multiparametric characterization of capsid-specific CD4 T cells was performed using customized MHC class II tetramers. Total and neutralizing antibodies targeting nHEV or eHEV particles were determined. HEV-specific CD4 T-cell frequencies and antibody titers are highest in individuals with acute infection and decline in a time-dependent process with an antigen hierarchy. HEV-specific CD4 T cells strongly target the ORF2-derived capsid and ORF3-specific CD4 T cells are hardly detectable. NAbs targeting nHEV are found in high titers while eHEV particles are less efficiently neutralized. Capsid-specific CD4 T cells undergo memory formation and stepwise contraction, accompanied by dynamic phenotypical and transcriptional changes over time. The viral capsid is the main target of HEV-specific CD4 T cells and antibodies in acute-resolving infection, correlating with efficient neutralization of nHEV. Capsid-specific immunity rapidly emerges followed by a stepwise contraction several years after infection. The interplay of CD4 T cells and neutralizing antibody responses is critical in the host defense against viral infections, yet little is known about their characteristics in hepatitis E virus (HEV) infection. We conducted a longitudinal study of immunocompetent individuals with acute and resolved HEV infection to understand the characteristics of HEV-specific CD4 T cells and neutralizing antibodies targeting different viral proteins and particles. We found that HEV-specific CD4 T cells mainly target capsid-derived epitopes. This correlates with efficient neutralization of naked virions while quasi-enveloped particles are less susceptible to neutralization. As individuals with pre-existing liver disease and immunocompromised individuals are at risk for fulminant or chronic courses of HEV infection, these individuals might benefit from the development of vaccination strategies which require a detailed knowledge of the composition and longevity of HEV-specific CD4 T-cell and antibody immunity.

Mucosal and systemic antigen-specific antibody responses correlate with protection against active tuberculosis in nonhuman primates

Increasing evidence supports that antibodies can protect against active tuberculosis (TB) but knowledge of potentially protective antigens, especially in the airways, is limited. The main objective of this study was to identify antigen-specific airway and systemic immunoglobulin isotype responses associated with the outcome of controlled latent Mycobacterium tuberculosis (Mtb) infection (LTBI) versus uncontrolled infection (TB) in nonhuman primates. In a case-control design, using non-parametric group comparisons with false discovery rate adjustments, we assessed antibodies in 57 cynomolgus macaques which, following low-dose airway Mtb infection, developed either LTBI or TB. We investigated airway and systemic IgG, IgA, and IgM responses in paired bronchoalveolar lavage and plasma samples prior to, two-, and 5-6-months post Mtb infection using an antigen-unbiased approach with Mtb glycan and proteome-wide microarrays. Macaques that developed LTBI (n=36) had significantly increased airway and plasma IgA reactivities to specific arabinomannan (AM) motifs prior to Mtb infection compared to those that developed TB (n=21; p<0.01, q<0.05). Furthermore, LTBI macaques had higher plasma IgG reactivity to protein MTB32A (Rv0125) early post Mtb infection (p<0.05) and increasing airway IgG responses to some proteins over time. Our results support a protective role of pre-existing mucosal (lung) and systemic IgA to specific Mtb glycan motifs, suggesting that prior exposure to nontuberculous mycobacteria could be protective against TB. They further suggest that IgG to Mtb proteins early post infection could provide an additional protective mechanism. These findings could inform TB vaccine development strategies. NIH/NIAID AI117927, AI146329, and AI127173 to JMA.

Serological response and immune-related adverse events following COVID-19 vaccination in cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

With the popularity of Coronavirus disease 2019 (COVID-19) vaccine and the development of vaccination strategies, the impact of COVID-19 vaccine on cancer patients receiving immune checkpoint inhibitors (ICIs) is still unclear. In the systematic review and meta-analysis of patients with ICIs, we assessed the serological response of cancer patients receiving COVID-19 vaccine, and explored the risk of immune related adverse events (irAEs). We searched PubMed, EMBASE and Cochrane Library as of 10 June 2023, and included cancer patients who received ICIs and COVID-19 vaccine. The systematic review and meta-analysis include cohort study, cross-sectional study and case report. The outcome included the serological response, Spike-specific T-cell response, irAEs and rare adverse events. When possible, the data were analysed by random effect analysis, and the statistical heterogeneity was assessed by Q-test and I2 statistics. We explored the sources of heterogeneity through L'Abbe plots, Galbraith radial plots, and sensitivity analysis. The publication bias was evaluated by Egger's, Begg's linear regression test and funnel plot, and the impact of publication bias was further analysed by trim and fill method. 27 studies were eligible (19 cohort studies, 1 cross-sectional study and 7 case reports), involving 8331 patients (with 4724 receiving ICIs). Most studies used mRNA vaccine (BNT162b2 or mRNA-1273). Compared with cancer patients receiving chemotherapy, cancer patients receiving ICIs were significantly more likely to have seroconversion (RR=1.05, 95%CI 1.01-1.10, P=0.02). There were no statistically significant differences in seroconversion rates when comparing cancer patients receiving ICIs with controls without cancer (RR=0.95, 95% CI 0.89-1.01, P=0.09) or with cancer patients receiving targeted therapy (RR=1.05, 95% CI 0.79-1.39, P=0.75). The incidence of irAEs in patients receiving ICIs before and after COVID-19 vaccination was (21.96%, 95%CI 16.66%-28.94%) and (14.88%, 95%CI 8.65%-25.57%), respectively. The most common irAEs were endocrine abnormalities, skin disorders, etc. The certainty of evidence was low in cancer patients with ICIs, compared with those receiving chemotherapy, and very low versus controls without cancer. Cancer patients treated with ICIs seem to be able to receive COVID-19 vaccine safely without increasing the incidence of irAEs.

Self-Assembled Multiepitope Nanovaccine Provides Long-Lasting Cross-Protection against Influenza Virus.

Seasonal influenza vaccines typically provide strain-specific protection and are reformulated annually, which is a complex and time-consuming process. Multiepitope vaccines, combining multiple conserved antigenic epitopes from a pathogen, can trigger more robust, diverse, and effective immune responses, providing a potential solution. However, their practical application is hindered by low immunogenicity and short-term effectiveness. In this study, multiple linear epitopes from the conserved stem domain of hemagglutinin and the ectodomain of matrix protein 2 are combined with the Helicobacter pylori ferritin, a stable self-assembled nanoplatform, to develop an influenza multiepitope nanovaccine, named MHF. MHF is prokaryotically expressed in a soluble form and self-assembles into uniform nanoparticles. The subcutaneous immunization of mice with adjuvanted MHF induces cross-reactive neutralizing antibodies, antibody-dependent cell-mediated cytotoxicity, and cellular immunity, offering complete protection against H3N2 as well as partial protection against H1N1. Importantly, the vaccine cargo delivered by ferritin triggers epitope-specific memory B-cell responses, with antibody level persisting for over 6 months post-immunization. These findings indicate that self-assembled multiepitope nanovaccines elicit potent and long-lasting immune responses while significantly reducing the risk of vaccine escape mutants, and offer greater practicality in terms of scalable manufacturing and genetic manipulability, presenting a promising and effective strategy for future vaccine development.

SARS-CoV-2 genomics and impact on clinical care for COVID-19.

The emergence and worldwide spread of SARS-CoV-2 during the COVID-19 pandemic necessitated the adaptation and rapid deployment of viral WGS and analysis techniques that had been previously applied on a more limited basis to other viral pathogens, such as HIV and influenza viruses. The need for WGS was driven in part by the low mutation rate of SARS-CoV-2, which necessitated measuring variation along the entire genome sequence to effectively differentiate lineages and characterize viral evolution. Several WGS approaches designed to maximize throughput and accuracy were quickly adopted by surveillance labs around the world. These broad-based SARS-CoV-2 genomic sequencing efforts revealed ongoing evolution of the virus, highlighted by the successive emergence of new viral variants throughout the course of the pandemic. These genomic insights were instrumental in characterizing the effects of viral mutations on transmissibility, immune escape and viral tropism, which in turn helped guide public health policy, the use of monoclonal antibody therapeutics and vaccine development strategies. As the use of direct-acting antivirals for the treatment of COVID-19 became more widespread, the potential for emergence of antiviral resistance has driven ongoing efforts to delineate resistance mutations and to monitor global sequence databases for their emergence. Given the critical role of viral genomics in the international effort to combat the COVID-19 pandemic, coordinated efforts should be made to expand global genomic surveillance capacity and infrastructure towards the anticipation and prevention of future pandemics.

Targeting the conserved coronavirus octamer motif GGAAGAGC is a strategy for the development of coronavirus vaccine

BackgroundCoronaviruses are pathogens of humans and animals that cause widespread and costly diseases. The development of effective strategies to combat the threat of coronaviruses is therefore a top priority. The conserved coronavirus octamer motif 5’GGAAGAGC3’ exists in the 3’ untranslated region of all identified coronaviruses. In the current study, we aimed to examine whether targeting the coronavirus octamer motif GGAAGAGC is a promising approach to develop coronavirus vaccine.MethodsPlaque assays were used to determine the titers of mouse hepatitis virus (MHV)-A59 octamer mutant (MHVoctm) and wild-type (wt) MHV-A59 (MHVwt). Western blotting was used for the determination of translation efficiency of MHVoctm and MHVwt. Plaque assays and RT-qPCR were employed to examine whether MHVoctm was more sensitive to interferon treatment than MHVwt. Weight loss, clinical signs, survival rate, viral RNA detection and histopathological examination were used to evaluate whether MHVoctm was a vaccine candidate against MHVwt infection in BALB/c mice.ResultsIn this study, we showed that (i) the MHVoctm with mutation of coronavirus octamer was able to grow to high titers but attenuated in mice, (ii) with the reduced multiplicity of infection (MOI), the difference in gene expression between MHVoctm and MHVwt became more evident in cultured cells, (iii) MHVoctm was more sensitive to interferon treatment than MHVwt and (iv) mice inoculated with MHVoctm were protected from MHVwt infection.ConclusionsBased on the results obtained from cultured cells, it was suggested that the synergistic effects of octamer mutation, multiplicity of infection and immune response may be a mechanism explaining the distinct phenotypes of octamer-mutated coronavirus in cell culture and mice. In addition, targeting the conserved coronavirus octamer motif is a strategy for development of coronavirus vaccine. Since the conserved octamer exists in all coronaviruses, this strategy of targeting the conserved octamer motif can also be applied to other human and animal coronaviruses for the development of coronavirus vaccines, especially the emergence of novel coronaviruses such as SARS-CoV-2, saving time and cost for vaccine development and disease control.