Vaccine Immunology Research Articles

Omicron neutralization character in patients with breast cancer and liver cancer after the nationwide omicron outbreak.

The surge in omicron variants has caused nationwide breakthrough infections in mainland China since the December 2022. In this study, we report the neutralization profiles of serum samples from the patients with breast cancer and the patients with liver cancer who had contracted subvariant breakthrough infections. In this real-world study, we enrolled 143 COVID-19-vaccinated (81 and 62 patients with breast and liver cancers) and 105 unvaccinated patients with cancer (58 and 47 patients with breast and liver cancers) after omicron infection. Anti-spike receptor binding domain (RBD) IgGs and 50% pseudovirus neutralization titer (pVNT50) for the preceding (wild type), circulating omicron (BA.4-BA.5, and BF.7), and new subvariants (XBB.1.5) were comprehensively analyzed. Patients with liver cancer receiving booster doses had higher levels of anti-spike RBD IgG against circulating omicron (BA.4-BA.5, and BF.7) and a novel subvariant (XBB.1.5) compared to patients with breast cancer after breakthrough infection. Additionally, all vaccinated patients produced higher neutralizing antibody titers against circulating omicron (BA.4-BA.5, and BF.7) compared to unvaccinated patients. However, the unvaccinated patients produced higher neutralizing antibody against XBB.1.5 than vaccinated patients after Omicron infection, with this trend being more pronounced in breast cancer than in liver cancer patients. Moreover, we found that there was no correlation between anti-spike RBD IgG against wildtype virus and the neutralizing antibody titer, but a positive correlation between anti-spike RBD IgG and the neutralizing antibody against XBB.1.5 was found in unvaccinated patients. Our study found that there may be differences in vaccine response and protective effect against COVID-19 infection in patients with liver and breast cancer. Therefore, we recommend that COVID-19 vaccine strategies should be optimized based on vaccine components and immunology profiles of different patients with cancer.

COVID-19 Vaccines in the Pediatric Population: A Focus on Cardiac Patients.

Due to the deleterious global impact of the COVID-19 pandemic, tremendous effort has been invested in the development of vaccines against the virus. Vaccine candidates are first tested in adult populations, a number of which have been approved for EUL by the WHO, and are in use across the USA and MENA region. The question remains whether these (or other) vaccines should be recommended to a neonatal, pediatric, and/or adolescent cohort. Incidence and severity of COVID-19 infection are low in pediatric, neonatal, and adolescent patients. Since both overall incidence and severity are lower in children than in adults, safety is an important consideration in vaccine approval for these age groups, in addition to efficacy and a decreased risk of transmission. The following review discusses vaccine immunology in children aged 0-18 years, with emphasis on the negative impact of the COVID-19 pandemic on the lives of children, considerations for pediatric vaccine approval, and available vaccines for pediatric cohorts along with a breakdown of the efficacy, advantages, and disadvantages for each. This review also contains current and future perspectives, as well as a section on the cardiovascular implications and related dynamics of pediatric COVID-19 vaccination.

Portable Nanopore sequencing solution for next-generation HIV drug resistance testing

BackgroundTackling HIV drug resistance is one of major challenges for ending AIDS epidemic, but the elevated expense of cutting-edge genomics hampers the advancement of HIV genotype testing for clinical care. MethodsWe developed a HIV genotype testing pipeline that centers on a cost-efficient portable Nanopore sequencer. Accuracy verification was conducted through comparison with parallel data obtained via fixed-site Pacbio sequencing. Our complete pol-gene sequencing strategy coupled with portable high-throughput sequencing was applied to identify drug resistance mutations across 58 samples sourced from the ART-treated Los Angeles General Medical Center Rand Schrader Clinic (LARSC) cohort (7 samples from 7 individuals) and the ART-naïve Center for HIV/AIDS Vaccine Immunology (CHAVI) cohort (51 samples from 38 individuals). ResultsA total of 472 HIV consensus sequences, each tagged with a unique molecular identifier, were produced from over 1.4 million bases acquired through portable Nanopore sequencing, which matched those obtained independently via Pacbio sequencing. With this desirable accuracy, we first documented the linkage of multidrug cross-resistance mutations across Integrase Strand Transfer inhibitors (INSTIs) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) from an individual failing a second-generation INSTI regimen. By producing more than 500 full-length HIV pol gene sequences in a single portable sequencing run, we detected Protease Inhibitor (PI), Nucleoside Reverse Transcriptase Inhibitor (NRTI), NNRTI and INSTI resistance mutations. All drug resistance mutations identified through portable sequencing were cross-validated using fixed-site Pacbio sequencing. ConclusionsOur accurate and affordable HIV drug resistance testing solution is adaptable for both individual patient care and large-scale surveillance initiatives.

Vaccine adjuvants: current status, research and development, licensing, and future opportunities.

Vaccines represent one of the most significant inventions in human history and have revolutionized global health. Generally, a vaccine functions by triggering the innate immune response and stimulating antigen-presenting cells, leading to a defensive adaptive immune response against a specific pathogen's antigen. As a key element, adjuvants are chemical materials often employed as additives to increase a vaccine's efficacy and immunogenicity. For over 90 years, adjuvants have been essential components in many human vaccines, improving their efficacy by enhancing, modulating, and prolonging the immune response. Here, we provide a timely and comprehensive review of the historical development and the current status of adjuvants, covering their classification, mechanisms of action, and roles in different vaccines. Additionally, we perform systematic analysis of the current licensing processes and highlights notable examples from clinical trials involving vaccine adjuvants. Looking ahead, we anticipate future trends in the field, including the development of new adjuvant formulations, the creation of innovative adjuvants, and their integration into the broader scope of systems vaccinology and vaccine delivery. The article posits that a deeper understanding of biochemistry, materials science, and vaccine immunology is crucial for advancing vaccine technology. Such advancements are expected to lead to the future development of more effective vaccines, capable of combating emerging infectious diseases and enhancing public health.

Association of lineage 4.2.2 of Mycobacterium tuberculosis with the 63-bp deletion variant of the mpt64 gene

ABSTRACT Tuberculosis (TB) remains the primary cause of death from an infectious disease worldwide. The MPT64 antigen assay is an expedited diagnostic method that is increasingly adopted in many TB diagnostic laboratories and clinical settings worldwide. However, the diagnostic accuracy of the MPT64 antigen assay is influenced by the presence of 63bp deletion variants within the mpt64 gene, and the potential association of this variant with the lineage or sub-lineage of Mycobacterium tuberculosis complex (MTBC) remains unverified. In this study, we analyzed the MPT64 antigen assay using isolates from the major lineage and sub-lineage of MTBC combined with whole-genome sequencing. Notably, we found a significant association between the 63bp deletion variant in the mpt64 gene and M. tuberculosis Lineage 4.2.2 (L4.2.2) globally. Phylogenetic analysis revealed that L4.2.2 isolates were divided into two clusters (Clades A and B). Importantly, all isolates within Clade A exhibited the 63bp deletion variant in the mpt64 gene. Furthermore, using the Bayesian Skyline population model, we observed that the effective population size of Clade A has remained relatively constant. These findings highlight that MPT64-based testing should be cautiously used, and MPT64 negative results should be validated using an alternative assay in regions where L4.2.2 isolates are prevalent, such as China and Vietnam. These L4.2.2 isolates with the 63bp deletion variant in mpt64 warrant greater consideration during the development of diagnostic tests and study of their immunomodulatory role. Overall, this study provides valuable insights into a better understanding of the virulence and diagnosis of MTBC isolates based on the MPT64 protein. IMPORTANCE To date, rapid diagnostic methods based on the MPT64 antigen assay are increasingly utilized to differentiate between non-tuberculous mycobacteria and TB disease in clinical settings. Furthermore, numerous novel techniques based on the MPT64 release assay are continuously being developed and applied for the identification of both pulmonary and extrapulmonary TB. However, the diagnostic accuracy of the MPT64 antigen assay is influenced by the presence of 63 bp deletion variants within the mpt64 gene. To our knowledge, this is the first report on the association between the 63 bp deletion variant in mpt64 and Mycobacterium tuberculosis L4.2.2 globally, which highlights the need for the cautious utilization of MPT64-based testing in regions where L4.2.2 isolates are prevalent, such as China and Vietnam, and MPT64 negative results should be confirmed with another assay. In addition, further studies on vaccine development and immunology based on MPT64 should consider these isolates with 63 bp deletion variant.

Learning-based sensitivity analysis and feedback design for drug delivery of mixed therapy of cancer in the presence of high model uncertainties

In this paper, a methodology is proposed that enables to analyze the sensitivity of the outcome of a therapy to unavoidable high dispersion of the patient specific parameters on one hand and to the choice of the parameters that define the drug delivery feedback strategy on the other hand. More precisely, a method is given that enables to extract and rank the most influent parameters that determine the probability of success/failure of a given feedback therapy for a given set of initial conditions over a cloud of realizations of uncertainties. Moreover predictors of the expectations of the amounts of drugs being used can also be derived. This enables to design an efficient stochastic optimization framework that guarantees safe contraction of the tumor while minimizing a weighted sum of the quantities of the different drugs being used. The framework is illustrated and validated using the example of a mixed therapy of cancer involving three combined drugs namely: a chemotherapy drug, an immunology vaccine and an immunotherapy drug. Finally, in this specific case, it is shown that dash-boards can be built in the 2D-space of the most influent state components that summarize the outcomes’ probabilities and the associated drug usage as iso-values curves in the reduced state space.

Vaccine Immunology in the context of COVID-19

Abstract Evidence at the start of the pandemic indicated that Māori and Pacific peoples were vulnerable to being disproportionately impacted and affected by COVID-19, indicating prioritisation with respect to COVID-19 vaccination and prevention efforts would be needed. Significant health inequities already existed for Māori and Pacific peoples prior to the COVID-19 outbreak, with the pandemic exacerbating pre-existing health inequities for vulnerable groups including Māori and Pacific peoples. An elimination strategy was pursued at the start of the COVID-19 pandemic in Aotearoa/New Zealand, a suppression strategy was then followed later. The initial lockdown periods helped keep the SARS-CoV-2 virus away while trying to get people vaccinated once the COVID-19 vaccines became available in Aotearoa/New Zealand. Efforts to spread mis/disinformation about the SARS-CoV-2 virus and COVID-19 vaccines were initiated early during the COVID-19 outbreak. The purpose of this work was to focus upon the immunological areas pertaining to the COVID-19 vaccines, to ensure appropriate scientific communication approaches that would support the COVID-19 vaccination roll-out. This work involved the utilisation of an online videoconferencing tool to support urgent communication efforts for the general public and lay audiences that would also support the countering of mis/disinformation about the COVID-19 vaccines in particular. Those who participated responded positively and indicating this approach helped demystify COVID-19 vaccines, explained how they worked, and encouraged vaccination. This work showed how appropriately presented COVID-19 vaccine information in the online setting could help counter mis/disinformation efforts. Wellington School of Medicine & Health Sciences, University of Otago.

Progress in vaccine development for infectious diseases-a Keystone Symposia report.

The COVID-19 pandemic has taught us many things, among the most important of which is that vaccines are one of the cornerstones of public health that help make modern longevity possible. While several different vaccines have been successful at stemming the morbidity and mortality associated with various infectious diseases, many pathogens/diseases remain recalcitrant to the development of effective vaccination. Recent advances in vaccine technology, immunology, structural biology, and other fields may yet yield insight that will address these diseases; they may also help improve societies' preparedness for future pandemics. On June 1-4, 2022, experts in vaccinology from academia, industry, and government convened for the Keystone symposium "Progress in Vaccine Development for Infectious Diseases" to discuss state-of-the-art technologies, recent advancements in understanding vaccine-mediated immunity, and new aspects of antigen design to aid vaccine effectiveness.

Emergence and antibody evasion of BQ, BA.2.75 and SARS-CoV-2 recombinant sub-lineages in the face of maturing antibody breadth at the population level.

The Omicron era of the COVID-19 pandemic commenced at the beginning of 2022 and whilst it started with primarily BA.1, it was latter dominated by BA.2 and the related sub-lineage BA.5. Following resolution of the global BA.5 wave, a diverse grouping of Omicron sub-lineages emerged derived from BA.2, BA.5 and recombinants thereof. Whilst emerging from distinct lineages, all shared similar changes in the Spike glycoprotein affording them an outgrowth advantage through evasion of neutralising antibodies. Over the course of 2022, we monitored the potency and breadth of antibody neutralization responses to many emerging variants in the Australian community at three levels: (i) we tracked over 420,000 U.S. plasma donors over time through various vaccine booster roll outs and Omicron waves using sequentially collected IgG pools; (ii) we mapped the antibody response in individuals using blood from stringently curated vaccine and convalescent cohorts. (iii) finally we determine the invitro efficacy of clinically approved therapies Evusheld and Sotrovimab. In pooled IgG samples, we observed the maturation of neutralization breadth to Omicron variants over time through continuing vaccine and infection waves. Importantly, in many cases, we observed increased antibody breadth to variants that were yet to be in circulation. Determination of viral neutralization at the cohort level supported equivalent coverage across prior and emerging variants with isolates BQ.1.1, XBB.1, BR.2.1 and XBF the most evasive. Further, these emerging variants were resistant to Evusheld, whilst increasing neutralization resistance to Sotrovimab was restricted to BQ.1.1 and XBF. We conclude at this current point in time that dominant variants can evade antibodies at levels equivalent to their most evasive lineage counterparts but sustain an entry phenotype that continues to promote an additional outgrowth advantage. In Australia, BR.2.1 and XBF share this phenotype and, in contrast to global variants, are uniquely dominant in this region in the later months of2022. Whilst the appearance of a diverse range of omicron lineages has led to primary or partial resistance to clinically approved monoclonal antibodies, the maturation of the antibody response across both cohorts and a large donor pools importantly observes increasing breadth in the antibody neutralisation responses over time with a trajectory that covers both current and known emerging variants. This work was primarily supported by Australian Medical Foundation research grants MRF2005760 (SGT, GM & WDR), Medical Research Future Fund Antiviral Development Call grant (WDR), the New South Wales Health COVID-19 Research Grants Round 2 (SGT & FB) and the NSW Vaccine Infection and Immunology Collaborative (VIIM) (ALC). Variant modeling was supported by funding from SciLifeLab's Pandemic Laboratory Preparedness program to B.M. (VC-2022-0028) and by the European Union's Horizon 2020 research and innovation programme under grant agreement no. 101003653 (CoroNAb) to B.M.

News in immunology.

The field of immunology has undergone a very significant development in recent decades, which has been reflected especially in the beginning of this millennium in significant advances in the understanding of the immune system and in the application of this knowledge in practice. The progress and acceleration of research and advances in the field of immunology was further prompt by the unexpected onset of the COVID-19 pandemic in 2020. The intense scientific work has not only led to the development of our understanding of the immune response to viruses, but also to the rapid conversion of this knowledge into practical pandemic management on a global scale, as exemplified by the development of vaccines against SARS-Cov-2 virus. The pandemic era has further contributed to the acceleration of the application of not only biological discoveries but also technological approaches into practical applications, such as use of advanced mathematics, computer science and, more recently, artificial intelligence which are all are adding to the advances that are significantly moving the field of immunology forward. In this communication, we present specific advances in particular areas of immunopathology, which are mainly allergy, immunodeficiency, immunity and infection, vaccination, autoimmune diseases and cancer immunology.

The evolution of personalized medicine: publications review

The personalized medicine is based on suggestion that each person has unique characteristics at molecular, physiological, ecological and behavioral levels. In case of development of disease one is to be treated considering these unique characteristics. This belief was to some extent confirmed by application of such newest technologies as DNA sequencing, proteomics, imaging protocols and application of wireless health monitoring devices which established large inter-individual differences.The purpose of the study was to summarize and systematize the results of publications on personalized medicine and its development.The search for scientific articles was carried out, including the published in peer-reviewed journals indexed in Pubmed, WoS, Scopus and RSCI. The review covers 49 articles considering new technologies that make possible the personalized medicine possible, new experience, modes of verification and application of individualized medications as well as potential means of treating people with fertility problems and infertility.The individualization of medical practice in particular cases is probably inevitable all the more the individual approach to patient becomes more effective and cost-effective. The accessibility of modern biomedical technologies, emergence of wireless monitoring devices allows to implement "personalized" approach to early, subclinical diagnostic, individualization of treatment in order to obtain maximal efficiency and minimal toxicity of therapy, prevention of relapse of disease and its prevention. The technology of cell avatars will permit to prognose development of diseases and, possibly, life expectancy too. The personalized approach in reproductology based on genetic research will permit to eliminate a number of hereditary, orphan diseases in XXI century the same way as studies in immunology and development of vaccines made it possible to eliminate black smallpox in XX century.Conclusion. The future challenges consist not only in looking for new manifold modes of characterizing patient, but also in personalization of therapy, development of individual medication and disease prevention schemes. It is presumably that applying more relevant models based on human cell cultures will allow not only to study pharmacodynamics of medications, but also to implement personalized selection of medication therapy, considering nature of disease and comorbid background of patient.

Rapamycin and inulin for booster vaccine response stimulation (RIVASTIM)—rapamycin: study protocol for a randomised, controlled trial of immunosuppression modification with rapamycin to improve SARS-CoV-2 vaccine response in kidney transplant recipients

Kidney transplant recipients are at an increased risk of severe COVID-19-associated hospitalisation and death. Vaccination has been a key public health strategy to reduce disease severity and infectivity, but the effectiveness of COVID vaccines is markedly reduced in kidney transplant recipients. Urgent strategies to enhance vaccine efficacy are needed.Methods: RIVASTIM-rapamycin is a multicentre, randomised, controlled trial examining the effect of immunosuppression modification prior to a third dose of COVID-19 vaccine in kidney transplant recipients who have failed to develop protective immunity to a 2-dose COVID-19 vaccine schedule. Participants will be randomised 1:1 to either remain on standard of care immunosuppression with tacrolimus, mycophenolate, and prednisolone (control) or cease mycophenolate and commence sirolimus (intervention) for 4 weeks prior to and following vaccination. The primary outcome is the proportion of participants in each trial arm who develop protective serological neutralisation of live SARS-CoV-2 virus at 4–6 weeks following a third COVID-19 vaccination. Secondary outcomes include SARS-CoV-receptor binding domain IgG, vaccine-specific immune cell populations and responses, and the safety and tolerability of sirolimus switch.Discussion: Immunosuppression modification strategies may improve immunological vaccine response. We hypothesise that substituting the mTOR inhibitor sirolimus for mycophenolate in a triple drug regimen will enhance humoral and cell-mediated responses to COVID vaccination for kidney transplant recipients.Trial registration: Australia New Zealand Clinical Trials Registry ACTRN12621001412820. Registered on 20 October 2021; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382891&isReview=true

Vaccination and COVID-19 Dynamics in Dialysis Patients.

Dialysis patients have a high mortality risk after coronavirus disease 2019 (COVID-19) and an altered immunologic response to vaccines, but vaccine clinical effectiveness remains unknown in this population. Using Bayesian multivariable spatiotemporal models, we estimated the association between vaccine exposure and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) severe infections (with hospital admission) in dialysis patients from simultaneous incidence in the general population. For dialysis patients, cases were reported within the French end-stage kidney disease REIN registry from March 11, 2020, to April 29, 2021, and vaccine exposure (first dose) was reported in weekly national surveys since January 2021. Cases in the general population were obtained from the national exhaustive inpatient surveillance system (SI-VIC database), and vaccination coverage (first dose) was obtained from the national surveillance system (VAC-SI database). During the first wave, incidence in dialysis patients was approximately proportional to the general population. However, we showed a lower relative incidence for dialysis patients during the second wave (compared with that observed in nondialysis patients), suggesting an effect of prevention measures. Moreover, from the beginning of the vaccination rollout, incidence in dialysis patients was lower compared with predictions based on the first and second waves. Adding vaccination coverages in dialysis and nondialysis patients as predictors allowed the reported cases to be fit correctly (3685 predicted cases, 95% confidence interval, 3552 to 3816, versus 3620 reported). Incidence rate ratios were 0.37 (95% confidence interval, 0.18 to 0.71) for vaccine exposure in dialysis patients and 0.50 (95% confidence interval, 0.40 to 0.61) per 10% higher in vaccination coverage in the same-age general population, meaning that vaccine exposure in dialysis patients and the general population was independently associated with lower hospitalization rate of dialysis patients. Our findings suggest that vaccination may yield a protective effect against severe forms of COVID-19 in dialysis patients, despite altered immunologic vaccine responses.

Vaccinations in Children and Adolescents Treated With Immune-Modifying Biologics: Update and Current Developments

Treatment with immune-modifying biologics has positively impacted disease control and quality of life in many patients with immune-mediated disorders. However, the higher susceptibility to common and opportunistic pathogens is of concern. Thus, immunization strategies to control vaccine-preventable diseases represent a critical issue in this population. However, limited data exist on the safety, immunogenicity, and efficacy of available vaccines in patients on biologics, particularly in children. Here, according to published literature and real-life experience and practice, we report the interim indications of the Italian Society of Pediatric Allergology and Immunology (SIAIP) Vaccine Committee and of the Italian Primary Immunodeficiency Network (IPINet) Centers on immunization of children and adolescents receiving biologics. Our aim is to provide a practical guidance for the clinician to ensure optimal protection for patients and the community.

Abstract P078: Synergistic immunotherapy effects of anti-COVID-19 and anti-cancer vaccines in preventing tumors and infections

Abstract To assure efficacy, safety and security of medicines and products including those of cancer and infection prevention ones, the concepts of immunology and immunotherapy, treatments, therapeutics, research, reviews, approvals and according agency, nation and world-wide managements are highly important. Often rationally planned combinations of U.S. Food and Drug Administration (USFDA) approved medicines in preventing or treating the same or similar or multiple diseases are realized to be pharmacologically and biologically effective in mechanisms and toxicologically safe in applications. Because, multiple mechanisms are simultaneously combined in enhancing systemic immunities within the permissible limits of the doses. In this work, the immunology and immunotherapy aspects of both anti-cancer vaccines and anti-COVID-19 vaccines are taken into account to prevent current and future occurrences of cancer and infectious diseases. Though the intended mechanisms of actions are only disease specific and are primarily different between anti-cancer and anti-COVID-19 vaccines, their combinations are worthwhile in providing synergistic effects against carcinogenesis, metastasis and infections. Based on the chemical, biological and pharmacological input and output information for both kinetics and dynamics of vaccines including mRNA-1273, BNT162b2, and JNJ-78436735 to prevent covid-19 are explored in combinations with anti-cancer vaccines including Human Papillomavirus (HPV) Vaccine and Hepatitis B Vaccine (HBV). In addition to safety and efficacy, mRNA, viral-vector, protein and antigen mechanisms, pH, vaccine-vaccine interactions, independent and combined dose regimens, toxicities, solubilities, intrinsic and extrinsic covariates were taken into account for careful planning of combinations. Simultaneous dual combinations from both groups were improved to three to five levels of combinations. It was realized that these combinations qualify for pre-clinical followed by clinical-investigations further. Also, these conclusions promised us to explore additional new and approved vaccines of these indications. Citation Format: Narayana Garimella. Synergistic immunotherapy effects of anti-COVID-19 and anti-cancer vaccines in preventing tumors and infections [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr P078.

COVID-19: pathogen characteristics, natural and adaptive immune response mechanisms, genetic diversity and distribution

COVID-19 is a pandemic disease caused by a member of the Coronaviridae family, a beta-2 coronavirus named SARS-CoV-2. The COVID-19 pandemic lasting about 19 months has caused serious damage to the health of people on our planet – by the 13 of July 2021, more than 187.9 000 000 patients have been diagnosed and more than 4.0 mln patients died from infection (> 2.0 %). Scientists around the world are actively investigating the critically important molecular-genetic aspects of the biology of the pathogen (genome RNA structure, proteins properties) that are important for understanding the disease mechanisms, as well as the mechanisms of individual and collective immunological protection and vaccines development with non-specific prophylactics.

COVID-19 vaccine research focusses on safety, efficacy, immunoinformatics, and vaccine production and delivery: a bibliometric analysis based on VOSviewer.

Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has affected tens of millions of people globally since it was declared a pandemic by the World Health Organization (WHO) on March 11, 2020. There is an urgent need for safe and effective preventive vaccines to curb this pandemic. A growing amount of related research has been published. This study aimed to provide the current status of COVID-19 vaccine using bibliometric analysis. We searched Embase.com and MEDLINE comprehensively and included articles, articles in press, reviews, short surveys, conference abstracts and conference papers about COVID-19 vaccine. VOSviewer1.6.11 (Leiden University, Leiden, Netherlands) was applied to perform the bibliometric analysis of these papers. A total of 1,312 papers were finally included. The BMJ has been the most popular journal in this field. The United States maintained a top position worldwide and has provided a pivotal influence, followed by China, India and United Kingdom. Among all the institutions, Harvard University was regarded as a leader for research collaboration. We analyzed the keywords and identified seven COVID-19 vaccine research hotspot clusters. COVID-19 vaccine research hotspots focus on clinical trials on vaccine safety and efficacy, research on vaccine immunology and immunoinformatics, and vaccine hesitancy. Our analysis results demonstrated that cooperation between countries, institutions, and authors were insufficient. The results suggested that clinical trials on vaccine safety, efficacy, immunology, immunoinformatics, production and delivery are research hotspots. Furthermore, we can predict that there will be a lot of research focusing on vaccine adverse reactions.

Risks of the European Reduction Program Incidence of Epidemic Parotitis Delayed Implementation in Russian Federation of WHO European Region

Analyzing mumps incidence worldwide, we revealed that all European countries are endemic to this viral infection. In the Russian Federation Epidemic Parotitis (EP) was taken under control since 1981, when mass pediatric vaccination has begun, followed by introduction in 1998 of children’s revaccination at the age of 6. During four decades the EP incidence in Russia has decreased 300-400 times, mortality and a number of residual phenomena have been eliminated. In 2002 the WHO Regional Committee has adopted a program to eliminate measles, reduce congenital rubella syndrome to 0.01 per 1 000 live births and the EP incidence to 1.0 or less per 100 000 population by 2010. For eighteen years the program has been delayed several times and still has not reached its goals. The main goal of our study was to evaluate humoral immunity in EP in patient cohorts of different age. We also detected specific immunoglobulin levels and dynamics in people from 3 mumps foci; identified objective causes interfering the epidemiological well-being of the Russian population, despite vaccination coverage of 95-96%. Our observations identified 2 risk groups with high mumps probability: subjects in age groups of 20 – 29 and 30 – 39 years old. The study demonstrated that the efficacy of vaccination, the intensity and duration of neutralizing mumps antibody retention is related directly to the personal immunological status and vaccine quality. In addition, our observations of subjects from 3 mumps foci as well as those, who we studied in our laboratory directly during the sporadic EP incidence increase, showed that stable, strong herd immunity cannot be achieved in long term only through pediatric vaccination and revaccination even with high population coverage. There always will be subjects non immune to EP. This number will grow after a certain time and result in an outbreak. The global goal is to monitor herd immunity both in Europe as a whole and in certain territories, including Russia. The main reason that the European community has not been able to reduce the EP incidence to goal point is the absence of a single international antibody standard that will allow to compare the individual defense level with the amount actually necessary for the protection, detected by standardized anti-mumps IgG test-system. We hope WHO will hear us and under its auspices a single certified international serum standard with known antibody level in IU will be created, and make real EP protection potential assessment possible.

Protective multi-epitope candidate vaccine for urinary tract infection

Urinary tract infections (UTIs) are induced by exogenous organisms including extraintestinal pathogenic such as Escherichia coli (ExPEC), Proteus mirabilis and Klebsiella pneumonia, which are closely related. These organisms can colonize in the urinary tract and cause UTIs. In this study, a cross-reactive multi-epitope vaccine was designed by two constructs to stimulate the immune system (CD8+ and CD4 + T cells) against ExPEC, Proteus mirabilis and Klebsiella pneumonia strains.Uropathogenic Escherichia coli (UPEC), Proteus mirabilis and Klebsiella pneumoniae are the main bacterial cause of UTI. They were used for designing experimental candidate vaccine, and their immunogenicity and protectivity were assessed. In this study, conserved antigens from their bacterial genomes were considered, and informatics-based immunological vaccine with cross-protective T and B-cells epitopes was designed and evaluated. The vaccine candidate was used as a broad immune system inducer, and its cross-protective immunity and protectivity were confirmed in in vivo experiments.

Emerging Concepts and Technologies in Vaccine Development.

Despite the success of vaccination to greatly mitigate or eliminate threat of diseases caused by pathogens, there are still known diseases and emerging pathogens for which the development of successful vaccines against them is inherently difficult. In addition, vaccine development for people with compromised immunity and other pre-existing medical conditions has remained a major challenge. Besides the traditional inactivated or live attenuated, virus-vectored and subunit vaccines, emerging non-viral vaccine technologies, such as viral-like particle and nanoparticle vaccines, DNA/RNA vaccines, and rational vaccine design, offer innovative approaches to address existing challenges of vaccine development. They have also significantly advanced our understanding of vaccine immunology and can guide future vaccine development for many diseases, including rapidly emerging infectious diseases, such as COVID-19, and diseases that have not traditionally been addressed by vaccination, such as cancers and substance abuse. This review provides an integrative discussion of new non-viral vaccine development technologies and their use to address the most fundamental and ongoing challenges of vaccine development.