ANTITUMOR IMMUNITY AND VACCINE EFFECT INDUCED BY IL-12 SYNERGIZES B7-1 GENE TRANSFECTED CELLS

Objective: To study the synergic effects of IL-12 and B7-1 transfectant on antitumor immunity in vivo. Methods: The retrovirus vector encoding mIL-12 and mB7-1 gene was tranfected into EL-4 thymic lymphoma cells respectively.The cells were used as tumor vaccine and the therapeutic effect was observed. Results: In contrast to the miceimmunized with EL-4/Wt or EL-4/Neo groups, thetumorigenicity of EL-4/IL-12 transfectant was decreased(P<0.001). The EL-4/IL-12 and EL-4/B7-1 cells irradiatedwith 60Co showed significant systematic protective effectsagainst the rechallenge of EL-4/Wt. 60Co irradiatedEL-4/IL-12 cells delayed the occurrence of tumor andprolonged the survival period of tumor bearing mice.Combination of the vaccines of EL-4/IL-12 and EL-4/B7-1 resulted in the enhanced therapeutic effect compared witheach single transfectant group (P<0.001). Conclusion: The results showed that IL-12 transduced cells could enhancethe antitumor immunity of host as cancer vaccine.Combination of the EL-4/IL-12 and EL-4/B7-1 transfectant could improve immunity of host and is a prospect cancervaccine.

HPV16E7-HSP70 Hybrid DNA Vaccine Induces E7-Specific Cytotoxic T Cells and Antitumor Immunity

Using human papillomavirus type 16 （HPV16） E7 as an antigen and Heat Shock Protein 70 as adjuvant, we constructed a DNA vaccine by linking HSP70 gene to E7^C91G; gene. Mice, after being immunized with E7^C91G;-HSP70, E7^C91G/HSP70, E7^C91G, and wild E7 DNA vaccines respectively, produced E7 specific CD8^＋ T-cell precursor frequencies of 280.33±2.52, 144.34±4.04, 164.34±5.13 and 82.33±3.51 respectively within every 1 × 10^5 mouse splenocytes. This proves that E7^C91G-HSP70 fusion vaccine can significantly enhance the E7 specific cellular immunity within the mice body（p〈0. 01）. After being immunized with E7^C91G-HSP70 fusion vaccine, tumor-bearing mice of the group being treated have significantly longer latency and survival periods, comparing with other three categories of E7 vaccines. Experiment shows that this vaccine has a significant effect on enhancing E7 positive tumor-treatment within mice body. After being immunized with E7^C91G-HSP70 vaccine, there were no pathological changes found in livers, kidneys and spleens of the mice, which proves that the vaccine is quite safe. After all, E7^C91G-HSP70 fusion vaccine has a much stronger tumor- treatment effect than thai of wild type E7 DNA vaccine.

Sex differences in SARS-CoV-2 infections,anti-viral immunity and vaccine responses

The COVID-19 pandemic has revealed sex-based differences in anti-viral responses,with a higher rate of SARS-CoV-2 infections as well as a higher rate of morbidity and mortality in men than in women.Males and females also show disparate immune responses to COVID-19 infection,which may be important contributors to lower rates of infection,disease severity and deaths in women than in men.Here,the authors review sex differences in SARS-CoV-2 infections,anti-viral immunity and vaccine responses,putting forth the importance of sex,the underappreciated variables in vaccine response and disease infectivity.

Radiation-based immunogenic vaccine combined with a macrophage“checkpoint inhibitor”for boosting innate and adaptive immunity against metastatic colon cancers

Immunogenic dying tumor cells hold promising prospects as cancer vaccines to activate systemic immunity against both primary and metastatic tumors.Especially,X-ray-induced dying tumor cells are rich in highly immunogenic tumor-associated antigens and self-generated dsDNA as potent adjuvants.However,we found that the X-ray induction process can result in the excessive exposure of phosphatidylserine in cancer vaccines,which can specifically bind with the MerTK receptor on macrophages,acting as a“checkpoint”to facilitate immune silence in the tumor microenvironment.Therefore,we developed a novel strategy combining X-ray-induced cancer vaccines with UNC2250,a macrophage MerTK“checkpoint inhibitor,”for treating peritoneal carcinomatosis in colon cancer.By incorporating UNC2250 into the treatment regimen,immunosuppressive efferocytosis of macrophages,which relies on MerTK-directed recognition of phosphatidylserine on vaccines,was effectively blocked.Consequently,the immune analysis revealed that this combination strategy promoted the maturation of dendritic cells and M1-like repolarization of macrophages,thereby simultaneously eliciting robust adaptive and innate immunity.This innovative approach utilizing X-ray-induced vaccines combined with a checkpoint inhibitor may provide valuable insights for developing effective cancer vaccines and immunotherapies targeting colon cancer.

Anti-tumor Immunity of Gene Vaccine with Nucleofection Technology

OBJECTIVE To observe enhancement of anti-tumor immunity by gene vaccine using nucleofection technology METHODS The technique of nucleofection was used to transfer effectively plasmid DNA into immature dendritic cells （iDCs）; we studied immune responses regulated by DNA vaccine using real-time quantitative polymerase chain reaction （PCR） and western-blotting to optimize the follow-up lymphocyte activation. The anti-tumor capacity of lymphocytes primed by DCs was analyzed using lactate dehydrogenase with a non-radioactive cytotoxicity assay.

The Tat Protein Enhances CTL Responses and Therapeutic Immunity of Gag-Specific Exosome-Targeted T Cell-Based Gag/Tat-Texo Vaccine in Transgenic HLA-A2 Mice

Human immunodeficiency virus type-1 (HIV-1) chronic infection causes millions of deaths each year. We previously developed a novel HIV-1 Gag-spe cific exosome (EXO)-targeted T cell-based vaccine (Gag-Texo) using ConAstimulated polyclonal CD8+T (ConA-T) cells armed with Gag-specific dendritic cell (DC)-released EXOs, and showed that Gag-Texo stimulated more efficient cytotoxic T lymphocyte (CTL) responses than DCs. Tat HIV-1 early regulatory protein possesses immunomodulatory and adjuvant properties. To enhance Gag-Texo immunogenicity, we generated Tat-engineered OVA/Tat Texo and Gag/Tat-Texo vaccines using ConA-T cells armed with EXOs release by DCs infected with recombinant OVA/Tat- and Gag/Tat-expressing adenoviruses (AdVOVA/Tat and AdVGag/Tat). We then assessed vaccination-stimulated CTL responses in naive mice, and therapeutic immunity in transgenic HLA-A2 mice bearing Gag/HLA-A2-expressing BL6-10OVA/A2 melanoma lung metastases. We demonstrate that the OVA/Tat-Texo vaccine enhances functional OVA-specific CTL responses, compared to the OVA-Texo vaccine, and broadens CTL responses recognizing the cryptic OVA epitope in C57BL/6 mice. Furthermore, we determine that the Gag/Tat-Texo not only stimulates more efficient CTL responses than Gag-Texo, but also induces enhanced therapeutic immunity. We show that, 30% of Gag/Tat-Texo-immunized mice are free of tumor lung-metastases, compared to all Gag-Texo-immunized mice displaying lung-metastasis. In addition, the average number of tumor lung metastases colonies (32/lung) in the Gag/Tat-Texo-immunized mice was also significantly lower than that (78/lung) observed in Gag-Texo-immunized mice. Taken together, this indicates that HIV-1 Gag/Tat-Texo capable of stimulating enhanced Gag-specific CTL responses and therapeutic immunity may become a new immunotherapeutic vaccine candidate for controlling virus in HIV-1 patients.

Waning Immunity after the BNT162b2 Vaccine in Israel

Background:In December 2020,Israel began a mass vaccination campaign against coronavirus disease 2019(Covid-19)by administering the BNT162b2 vaccine,which led to a sharp curtailing of the outbreak.After a period with almost no cases of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,a resurgent Covid-19 outbreak began in mid-June 2021.Possible reasons for the resurgence were reduced vaccine effectiveness against the delta(B.1.617.2)variant and waning immunity.The extent of waning immunity of the vaccine against the delta variant in Israel is unclear.

Covid-19 vaccines and Community Immunity

This short review analyzed the present status of different Covid-19 vaccine,their utility in Covid-19 control and as a tool of herd or community immunity.Most of the vaccines approved to date have insufficient data to predict their protective potential against COVID-19 virus infection and carriage(potential as silent spreader).We also not know the period of protective immunity and their ability to protect against variants of viruses emerging fast.The vaccine at the most can be used as personal protective shots against COVID-19.

mRNA vaccines:a new era in vaccine development

The advent of RNA therapy,particularly through the development of mRNA cancer vaccines,has ushered in a new era in the field of oncology.This article provides a concise overview of the key principles,recent advancements,and potential implications of mRNA cancer vaccines as a groundbreaking modality in cancer treatment.mRNA cancer vaccines represent a revolutionary approach to combatting cancer by leveraging the body’s innate immune system.These vaccines are designed to deliver specific mRNA sequences encoding cancer-associated antigens,prompting the immune system to recognize and mount a targeted response against malignant cells.This personalized and adaptive nature of mRNA vaccines holds immense potential for addressing the heterogeneity of cancer and tailoring treatments to individual patients.Recent breakthroughs in the development of mRNA vaccines,exemplified by the success of COVID-19 vaccines,have accelerated their application in oncology.The mRNA platform’s versatility allows for the rapid adaptation of vaccine candidates to various cancer types,presenting an agile and promising avenue for therapeutic intervention.Clinical trials of mRNA cancer vaccines have demonstrated encouraging results in terms of safety,immunogenicity,and efficacy.Pioneering candidates,such as BioNTech’s BNT111 and Moderna’s mRNA-4157,have exhibited promising outcomes in targeting melanoma and solid tumors,respectively.These successes underscore the potential of mRNA vaccines to elicit robust and durable anti-cancer immune responses.While the field holds great promise,challenges such as manufacturing complexities and cost considerations need to be addressed for widespread adoption.The development of scalable and cost-effective manufacturing processes,along with ongoing clinical research,will be pivotal in realizing the full potential of mRNA cancer vaccines.Overall,mRNA cancer vaccines represent a cutting-edge therapeutic approach that holds the promise of transforming cancer treatment.As research progresses,addressing challenges and refining manufacturing processes will be crucial in advancing these vaccines from clinical trials to mainstream oncology practice,offering new hope for patients in the fight against cancer.

Antibodies elicited by Newcastle disease virus-vectored H7N9 avian influenza vaccine are functional in activating the complement system

H7N9 subtype avian influenza virus poses a great challenge for poultry industry.Newcastle disease virus(NDV)-vectored H7N9 avian influenza vaccines(NDV_(vec)H7N9)are effective in disease control because they are protective and allow mass administration.Of note,these vaccines elicit undetectable H7N9-specific hemagglutination-inhibition(HI)but high IgG antibodies in chickens.However,the molecular basis and protective mechanism underlying this particular antibody immunity remain unclear.Herein,immunization with an NDV_(vec)H7N9 induced low anti-H7N9 HI and virus neutralization titers but high levels of hemagglutinin(HA)-binding IgG antibodies in chickens.Three residues(S150,G151 and S152)in HA of H7N9 virus were identified as the dominant epitopes recognized by the NDV_(vec)H7N9 immune serum.Passively transferred NDV_(vec)H7N9 immune serum conferred complete protection against H7N9 virus infection in chickens.The NDV_(vec)H7N9 immune serum can mediate a potent lysis of HA-expressing and H7N9 virus-infected cells and significantly suppress H7N9 virus infectivity.These activities of the serum were significantly impaired after heat-inactivation or treatment with complement inhibitor,suggesting the engagement of the complement system.Moreover,mutations in the 150-SGS-152 sites in HA resulted in significant reductions in cell lysis and virus neutralization mediated by the NDV_(vec)H7N9 immune serum,indicating the requirement of antibody-antigen binding for complement activity.Therefore,antibodies induced by the NDV_(vec)H7N9 can activate antibody-dependent complement-mediated lysis of H7N9 virus-infected cells and complement-mediated neutralization of H7N9 virus.Our findings unveiled a novel role of the complement in protection conferred by the NDV_(vec)H7N9,highlighting a potential benefit of engaging the complement system in H7N9 vaccine design.

Toward innovative veterinary nanoparticle vaccines

Nanoparticles are significant for veterinary vaccine development because they are safer and more effective than conventional formulations.One promising area of research involves self-assembled protein nanoparticles(SAPNs),which have shown potential for enhancing antigen-presenting cell uptake,B-cell activation,and lymph node trafficking.Numerous nanovaccines have been utilized in veterinary medicine,including natural self-assembled protein nanoparticles,rationally designed self-assembled protein nanoparticles,animal virus-derived nanoparticles,bacteriophagederived nanoparticles,and plant-derived nanoparticles,which will be discussed in this review.SAPN vaccines can produce robust cellular and humoral immune responses and have been shown to protect against various animal infectious diseases.This article attempts to summarize these diverse nanovaccine types and their recent research progress in the field of veterinary medicine.Furthermore,this paper highlights their disadvantages and methods for improving their immunogenicity.

Does Herd Immunity Reduce the Risk of Contracting COVID-19?

Herd immunity is often considered a measure to protect a whole community or population from disease if the vaccination threshold is met. Using the demographic and COVID-19 infection data from the state of Pennsylvania, United States, the study aimed to determine if herd immunity by vaccination is an effective way to reduce the spread of the COVID-19 virus. The Pennsylvania counties were split into two groups based on qualification of herd immunity: counties that met the COVID-19 herd immunization rate of 70% and counties that did not. The ANOVA test was used to analyze the difference between the groups with and without herd immunity by the COVID-19 vaccine. The results demonstrated that there was no significant statistical difference between counties that did achieve and those that did not achieve the herd immunity threshold for the COVID-19 vaccine. On the other hand, it was observed that there had been a significant decrease in positive cases between 2020 and 2023. This decline can be attributed to the overall protection by the vaccination and adaptability to the disease, not specifically due to herd immunity alone. Ultimately, these outcomes suggest that herd immunity cannot reduce the risk of contracting COVID-19. Increased efforts to get vaccinated should be implemented to protect the general community and a wider scope of age.

Analysis of Epidemiological Characteristics of Varicella Before and After the Implementation of the Two-dose Varicella Vaccine Immunization Program in Banan District of Chongqing City

Objective:To explore the changes in the epidemiological characteristics of varicella before and after implementing the two-dose varicella vaccine(VarV)immunization program in the Banan District of Chongqing and to provide a reference for future epidemic prevention and control.Methods:The data of reported varicella cases in Banan District from 2014 to 2023 were collected and analyzed using the China Disease Prevention and Control Information System.Descriptive epidemiological methods were employed to assess the changes in the reported incidence of varicella before(2014-2018)and after(2019-2023)the implementation of the two-dose VarV immunization program.Results:The average annual reported incidence rate of varicella in Banan District from 2014 to 2023 was 81.53 per 100,000.From 2014 to 2018,the reported incidence rate showed an upward trend year by year(trend x2=223.96,P<0.05).However,the reported incidence rate decreased from 2019 to 2023(trend x?=189.51,P<0.05).Before and after the adjustment of the immunization program,the reported incidence rate for the 5-9 years old group was 774.62 per 100,000 and 476.98 per 100,000,respectively,with a statistically significant difference(x2=161.26,P<0.05).The onset of varicella showed a bimodal distribution,with peak incidence periods in May-June and October-December.From 2014 to 2023,a total of 155,181 doses of VarV were administered in Banan District.The estimated annual vaccination rate for the first varicella vaccine(VarV1)from 2019 to 2023 was 86.28%,and for the second dose(VarV2)was 59.18%.The primary vaccination targets were the 5-9-year-old group,accounting for 64.21%.Conclusion:After implementing the two-dose VarV immunization program in Banan District,the vaccination rate increased yearly,and the reported incidence of varicella showed a downward trend.The incidence rate of varicella in children aged 5-9 years reduced significantly,but the overall downward trend for the entire population was not as pronounced.Therefore,it is necessary to increase the vaccination rate of VarV2.

A Case of Investigation and Diagnosis of Immune Thrombocytopenic Purpura After Vaccination of COVID-19 Inactivated Vaccine

Objective:Analyze the relationship between inoculating one case of the COVID-19 inactivated vaccine(Vero cell)and immune thrombocytopenic purpura to provide a reference for the standardized handling of adverse events following immunization.Methods:According to the"National Monitoring Program for Suspected Adverse Reactions to Vaccinations,"an on-site investigation,data collection and analysis,expert group diagnosis,and medical association assessment were conducted on a case of immune thrombocytopenic purpura in District A of Chongqing after vaccination with the inactivated COVID-19 vaccine.The assessment report was delivered to the three relevant parties,the case was reviewed,and the experience was summarized.Results:The investigation and diagnosis by the district-level vaccination abnormal reaction expert group concluded that the disease that occurred after vaccination with the COVID-19 inactivated vaccine was secondary immune thrombocytopenic purpura,an abnormal reaction to the vaccination.The medical damage was classified as Level II Grade B.The vaccine production enterprise raised objections to this conclusion.After re-assessment by the municipal-level medical association,the conclusion was consistent with that of the district-level medical association.The vaccine production enterprise did not raise any further objections.Conclusion:Through active collaboration among district and municipal-level medical associations,disease control institutions,and vaccination units,the recipients have been promptly and effectively treated,providing financial support for their subsequent treatment and safeguarding their rights.The investigation and disposal procedures for adverse events following immunization in Chongqing are clear,and the mechanism is sound.It is necessary to continue strengthening the monitoring of adverse events following immunization according to the existing plan and to ensure timely and standardized handling.Simultaneously,it is crucial to strengthen vaccine management and vaccination management.

Key Factors to Consider When Introducing a New Vaccine in Low-Income Settings: Lessons from Malawi Expanded Program on Immunization

Introduction: As new vaccines become available, countries must assess the relevance to introduce them into their vaccination schedules. Malawi has recently introduced several new vaccines and plans to introduce more. This study was conducted to identify key factors that need to be considered when deciding to introduce a new vaccine and current challenges faced by low and middle income countries using Malawi as an example. Methodology: The study employed a desk review approach, examining published literature from various sources such as PubMed, Medline, and Google Scholar. Policy documents from organizations like the World Health Organization, GAVI the Alliance, and the Ministry of Health for Malawi were also included. A total of 99 articles and documents on new vaccine introduction, challenges of immunization, policy documents in immunization and health systems strengthening were included. The review focused on addressing five key areas critical to new vaccine introduction namely: the need for a vaccine, availability of the vaccine, safety and effectiveness of the vaccine, demand for the vaccine, and the prudent use of public or private funds. Results: Malawi considered the burden of cervical cancer and the significance of malaria in the country when introducing the HPV and malaria vaccines. The country opted for vaccines that can be handled by the cold chain capacity and available human resources. Despite that malaria vaccine and Typhoid Conjugate Vaccine trials were done in country, there are limited vaccine safety and efficacy trials conducted in Malawi, leading to a reliance on WHO-prequalified vaccines. Demand for newly introduced vaccines varied, with high demand for Oral Cholera Vaccine during a cholera outbreak, while demand for COVID-19 vaccines decreased over time. Although cost-effectiveness studies were limited in the country, 2 studies indicated that Typhoid Conjugate Vaccine and malaria vaccine would be cost effective. All these have been implemented despite having challenges like lack of accurate surveillance data, inadequate cold chain capacity, limited safety and efficacy vaccine clinical trials, political influence, and limited funding. Conclusion: Despite several challenges Malawi set a good example of the careful considerations required before introducing a new vaccine. The process involves data review, priority setting, precise planning, and consultation with stakeholders. Low-income countries should invest in vaccine safety, efficacy, and cost-effectiveness trials.

Omicron variants breakthrough infection elicited higher specific memory immunity than third dose booster in healthy vaccinees

Homologous booster,heterologous booster,and Omicron variants breakthrough infection(OBI)could improve the humoral immunity against Omicron variants.Questions concerning about memory B cells(MBCs)and T cells immunity against Omicron variants,features of long-term immunity,after booster and OBI,needs to be explored.Here,comparative analysis demonstrate antibody and T cell immunity against ancestral strain,Delta and Omicron variants in Omicron breakthrough infected patients(OBIPs)are comparable to that in Ad5-nCoV boosted healthy volunteers(HVs),higher than that in inactivated vaccine(InV)boosted HVs.However,memory B cells(MBCs)immunity against Omicron variants was highest in OBIPs,followed by Ad5-nCoV boosted and InV boosted HVs.OBIPs and Ad5-nCoV boosted HVs have higher classical MBCs and activated MBCs,and lower naïve MBCs and atypical MBCs relative to both vaccine boosted HVs.Collectively,these data indicate Omicron breakthrough infection elicit higher MBCs and T cells against SARS-CoV-2 especially Omicron variants relative to homologous InV booster and heterologous Ad5-nCoV booster.

Personalized pancreatic cancer therapy:from the perspective of mRNA vaccine

Pancreatic cancer is characterized by inter-tumoral and intra-tumoral heterogeneity,especially in genetic alteration and microenvironment.Conventional therapeutic strategies for pancreatic cancer usually suffer resistance,highlighting the necessity for personalized precise treatment.Cancer vaccines have become promising alternatives for pancreatic cancer treatment because of their multifaceted advantages including multiple targeting,minimal nonspecific effects,broad therapeutic window,low toxicity,and induction of persistent immunological memory.Multiple conventional vaccines based on the cells,microorganisms,exosomes,proteins,peptides,or DNA against pancreatic cancer have been developed;however,their overall efficacy remains unsatisfactory.Compared with these vaccine modalities,messager RNA(mRNA)-based vaccines offer technical and conceptional advances in personalized precise treatment,and thus represent a potentially cutting-edge option in novel therapeutic approaches for pancreatic cancer.This review summarizes the current progress on pancreatic cancer vaccines,highlights the superiority of mRNA vaccines over other conventional vaccines,and proposes the viable tactic for designing and applying personalized mRNA vaccines for the precise treatment of pancreatic cancer.

Evolution of Acquired Humoral Immunity after Full Vaccination against SARS-CoV-2. IgG Levels in Healthcare Workers at 6 and 9 Months

Background: The COVID-19 pandemic continues to be a major worldwide health problem. The present study aims to contribute to surveillance of the immune and clinical response of vaccines to SARS-CoV-2. Methods: Observational medication study on acquired immunity and effectiveness of vaccines. Population: 620 workers in the health service of Almansa (Spain). Representative sample of 150 individuals. Sociodemographic, clinical, and epidemiological data and samples were recorded to determine anti-SARS-CoV-2 serum IgG levels 6 and 9 months after vaccination with Pfizer. Results: Mean age 46.45 years;76% women;85.1% working in a hospital. 19.3% had had COVID-19 in the year prior to vaccination. 96.7% were fully vaccinated with Pfizer/BioNTech. At 6 months, 100% seropositivity and mean IgG levels of 3017.2 AU/ml. Significant variations in IgG levels in individuals with prior COVID-19 infection and smokers. At 9 months, 99.3% remained seropositive;2.8% infected after vaccination. The repeated measures analysis showed a difference in means of 669.0 AU/ml (significant decrease in IgG levels of 28.9%). Conclusion: Antibody levels remained positive 6 and 9 months after vaccination, although IgG levels were found to decay.

Protective efficacy evaluation of immunogenic protein AHA_3793 of Aeromonas hydrophila as vaccine candidate for largemouth bass Micropterus salmoides

Aeromonas hydrophila is a Gram-negative pathogen that can infect various fish,including largemouth bass(Micropterus salmoides),which have caused huge economic losses.In present study,largemouth bass anti-A.hydrophila antibodies were produced,then a highly immunogenic outer membrane proteins,AHA_3793,was identified by combined western blotting and mass spectrometry analysis.Moreover,AHA_3793 was expressed,and its immunogenicity was further verified by western blotting.Subsequently,the protective efficacy of AHA_3793 were evaluated in largemouth bass.The results showed that rAHA_3793 could produce a relative percentage survival(RPS)of 61.76% for largemouth bass against A.hydrophila challenge.ELISA analysis showed the specific serum antibodies of largemouth bass against rAHA_3793 and A.hydrophila in vaccinated group in weeks 4 and 5 after immunization were significantly higher than those in control group,which suggested that rAHA_3793 induced production of specific serum antibodies against rAHA_3793 and A.hydrophila.The qRT-PCR analysis showed that expressions of CD4-2 and MHC Ⅱα were also significantly up-regulated after immunization.These results collectively demonstrated that rAHA_3793 could induce a strong humoral immune response of largemouth bass,and then produce high immune protection ef fects against A.hydrophila infection.