[Efficacy and safety of patients immunization with chronic obstructive pulmonary disease with monoclonal antibodies].

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by a high level of morbidity and mortality and is associated with significant social and economic damage to the health system and society. COPD and COVID-19 have many potentially negative relationships that can lead to worse outcomes of COVID-19, including impaired lung function, old age and the presence of concomitant diseases Aim. To assess efficacy and safety of the drug Tixagevimab + Cilgavimab for the pre-contact prevention of COVID-19 infection in patients with COPD. MATERIAL AND METHODS: A total of 324 male patients were included in the study, who were treated or monitored at the Regional Clinic Hospital №3 and the Regional Pulmonological Center of Chelyabinsk in April-May 2022. The main endpoints of observation, for 3 and 6 months, to assess the effectiveness were the dynamics of shortness of breath according to The Modified Medical Research Council Dyspnea Scale - mMRC, the The forced expiratory volume in 1 second, the number of exacerbations, emergency calls, hospitalizations, polymerase chain reaction for SARS-CoV-2. Local and general reactions after immunization were evaluated. The drug Evusheld (150 mg Tixsagevimab +150 mg Cilgavimab, AstraZeneca) was used for immunization. RESULTS AND CONCLUSION: The effectiveness of pre-contact prevention of COVID-19 was 88.8%. The administration of the drug does not provoke an exacerbation of the underlying disease. The main clinical and functional indicators have positive dynamics by the 6th month of follow-up. The drug is well tolerated and has no significant both early and late complications.

Imprecision in adverse event reports following immunization against HPV in Japan and COVID-19 in the USA, UK, and Japan-and the effects of vaccine hesitancy and government policy.

INTRODUCTION: Erroneous reports of adverse events following immunization (AEFIs) likely exacerbated the 2013 collapse of Japan's HPV immunization program. A similar phenomenon characterized the first months of COVID-19 immunization programs in the USA, UK, and Japan with high rates of reported anaphylaxis. These reports illustrate the susceptibility of supposedly objective medical judgments to public anxiety. PURPOSE AND METHODS: This study documents inaccuracies in reported AEFIs using three quantitative methods. RESULTS: One of these quantitative methods revealed that false-positive rates for anaphylaxis reports following HPV and later COVID-19 vaccination ranged from 74 to 91 percent. However, unlike HPV vaccinations in Japan, anaphylaxis reports following COVID-19 vaccines fell in Japan, the USA and the UK in the latter months of 2021. Nevertheless, false-positive rates for anaphylaxis reports remained high, suggesting a high degree of imprecision in serious AEFI reports from many countries for many vaccines. Japan's HPV immunization program indicates that media reports, patient hesitancy, healthcare providers' perspectives on vaccine safety, and consistency of government messaging, all influence report number and accuracy. A parallel publication analyzes in depth how such factors affect AEFI reports. CONCLUSION: Confidence in the safety of the COVID-19 vaccines may have been bolstered trough rapid monitoring of AEFI reports and communication of these findings. This may partly explain the different trajectories of serious AEFI following HPV immunizations in Japan and COVID-19 immunizations in the USA, UK, and Japan.

Mucosal immunization with lactiplantibacillus plantarum-displaying recombinant SARS-CoV-2 epitopes on the surface induces humoral and mucosal immune responses in mice.

BACKGROUND: The use of probiotic lactic acid bacteria as a mucosal vaccine vector is considered a promising alternative compared to the use of other microorganisms because of its "Generally Regarded as Safe" status, its potential adjuvant properties, and its tolerogenicity to the host. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19), is highly transmissible and pathogenic. This study aimed to determine the potential of Lactiplantibacillus plantarum expressing SARS-CoV-2 epitopes as a mucosal vaccine against SARS-CoV-2. RESULTS: In this study, the possible antigenic determinants of the spike (S1-1, S1-2, S1-3, and S1-4), membrane (ME1 and ME2), and envelope (E) proteins of SARS-CoV-2 were predicted, and recombinant L. plantarum strains surface-displaying these epitopes were constructed. Subsequently, the immune responses induced by these recombinant strains were compared in vitro and in vivo. Most surface-displayed epitopes induced pro-inflammatory cytokines [tumor necrosis factor alpha (TNF-α and interleukin (IL)-6] and anti-inflammatory cytokines (IL-10) in lipopolysaccharide-induced RAW 264.7, with the highest anti-inflammatory to pro-inflammatory cytokine ratio in the S1-1 and S1-2 groups, followed by that in the S1-3 group. When orally administered of recombinant L. plantarum expressing SARS-CoV-2 epitopes in mice, all epitopes most increased the expression of IL-4, along with induced levels of TNF-α, interferon-gamma, and IL-10, specifically in spike protein groups. Thus, the surface expression of epitopes from the spike S1 protein in L. plantarum showed potential immunoregulatory effects, suggesting its ability to potentially circumvent hyperinflammatory states relevant to monocyte/macrophage cell activation. At 35 days post immunization (dpi), serum IgG levels showed a marked increase in the S1-1, S1-2, and S1-3 groups. Fecal IgA levels increased significantly from 21 dpi in all the antigen groups, but the boosting effect after 35 dpi was explicitly observed in the S1-1, S1-2, and S1-3 groups. Thus, the oral administration of SARS-CoV-2 antigens into mice induced significant humoral and mucosal immune responses. CONCLUSION: This study suggests that L. plantarum is a potential vector that can effectively deliver SARS-CoV-2 epitopes to intestinal mucosal sites and could serve as a novel approach for SARS-CoV-2 mucosal vaccine development.

Broadly neutralizing antibodies against sarbecoviruses generated by immunization of macaques with an AS03-adjuvanted COVID-19 vaccine.

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has placed an imperative on the development of countermeasures that provide broad protection against SARS-CoV-2 and related sarbecoviruses. Here, we identified extremely potent monoclonal antibodies (mAbs) that neutralized multiple sarbecoviruses from macaques vaccinated with AS03-adjuvanted monovalent subunit vaccines. Longitudinal analysis revealed progressive accumulation of somatic mutation in the immunoglobulin genes of antigen-specific memory B cells (MBCs) for at least 1 year after primary vaccination. Antibodies generated from these antigen-specific MBCs at 5 to 12 months after vaccination displayed greater potency and breadth relative to those identified at 1.4 months. Fifteen of the 338 (about 4.4%) antibodies isolated at 1.4 to 6 months after the primary vaccination showed potency against SARS-CoV-2 BA.1, despite the absence of serum BA.1 neutralization. 25F9 and 20A7 neutralized authentic clade 1 sarbecoviruses (SARS-CoV, WIV-1, SHC014, SARS-CoV-2 D614G, BA.1, and Pangolin-GD) and vesicular stomatitis virus-pseudotyped clade 3 sarbecoviruses (BtKY72 and PRD-0038). 20A7 and 27A12 showed potent neutralization against all SARS-CoV-2 variants and multiple Omicron sublineages, including BA.1, BA.2, BA.3, BA.4/5, BQ.1, BQ.1.1, and XBB. Crystallography studies revealed the molecular basis of broad and potent neutralization through targeting conserved sites within the RBD. Prophylactic protection of 25F9, 20A7, and 27A12 was confirmed in mice, and administration of 25F9 particularly provided complete protection against SARS-CoV-2, BA.1, SARS-CoV, and SHC014 challenge. These data underscore the extremely potent and broad activity of these mAbs against sarbecoviruses.

AVP deficiency (central diabetes insipidus) following immunization with anti-COVID-19 BNT162b2 Comirnaty vaccine in adolescents: A case report.

Introduction: The coronavirus disease 19 (COVID-19) pandemic has prompted the development of new vaccines to reduce the morbidity and mortality associated with this disease. Recognition and report of potential adverse effects of these novel vaccines (especially the urgent and life-threatening ones) is therefore essential. Case presentation: A 16-year-old boy presented to the Paediatric Emergency Department with polyuria, polydipsia and weight loss over the last four months. His past medical history was unremarkable. Onset of symptoms was referred to be few days after first dose of anti-COVID-19 BNT162b2 Comirnaty vaccine and then worsened after the second dose. The physical exam was normal, without neurological abnormalities. Auxological parameters were within normal limits. Daily fluid balance monitoring confirmed polyuria and polydipsia. Biochemistry laboratory analysis and urine culture were normal. Serum osmolality was 297 mOsm/Kg H2O (285-305), whereas urine osmolality was 80 mOsm/Kg H2O (100-1100), suggesting diabetes insipidus. Anterior pituitary function was preserved. Since parents refused to give consent to water deprivation test, treatment with Desmopressin was administered and confirmed ex juvantibus diagnosis of AVP deficiency (or central diabetes insipidus). Brain MRI revealed pituitary stalk thickening (4 mm) with contrast enhancement, and loss of posterior pituitary bright spot on T1 weighted imaging. Those signs were consistent with neuroinfundibulohypophysitis. Immunoglobulin levels were normal. Low doses of oral Desmopressin were sufficient to control patient's symptoms, normalizing serum and urinary osmolality values and daily fluid balance at discharge. Brain MRI after 2 months showed stable thicken pituitary stalk and still undetectable posterior pituitary. Due to persistence of polyuria and polydipsia, therapy with Desmopressin was adjusted by increasing dosage and number of daily administrations. Clinical and neuroradiological follow-up is still ongoing. Conclusion: Hypophysitis is a rare disorder characterized by lymphocytic, granulomatous, plasmacytic, or xanthomatous infiltration of the pituitary gland and stalk. Common manifestations are headache, hypopituitarism, and diabetes insipidus. To date, only time correlation between SARS-CoV-2 infection and development of hypophysitis and subsequent hypopituitarism has been reported. Further studies will be needed to deepen a possible causal link between anti-COVID-19 vaccine and AVP deficiency.

The long-term antibody response after SARS-CoV-2 prime-boost vaccination in healthy individuals. The positive influence of extended between-dose intervals and heterologous schedule.

Introduction: Anti-COVID vaccination in Argentina was carried out using different protocols and variations in periods between administrations, as well as combinations of different vaccine platforms. Considering the relevance of the antibody response in viral infections, we analyzed anti-S antibodies in healthy people at different points of time following the Sputnik immunization procedure. Methods: We attended the vaccination centers in the city of Rosario, which had shorter versus longer intervals between both doses. A total of (1021) adults with no COVID-compatible symptoms (throughout the study period) were grouped according to the gap between both vaccine doses: 21 (Group A, n=528), 30 (Group B, n=147), and 70 days (Group C, n=82), as well as an additional group of individuals with heterologous vaccination (Sputnik/Moderna, separated by a 107-day interval, group D, n=264). Results and conclusions: While there were no between-group differences in baseline levels of specific antibodies, data collected several weeks after administering the second dose showed that group D had the highest amounts of specific antibodies, followed by values recorded in Groups C, B, and A. The same pattern of group differences was seen when measuring anti-S antibodies at 21 or 180 days after the first and second doses, respectively. Delayed between-dose intervals coexisted with higher antibody titers. This happened even more when using a prime-boost heterologous schedule.

Orf virus DNA prime-protein boost strategy is superior to adenovirus-based vaccination in mice and sheep.

Contagious ecthyma (Orf), an acute and highly contagious zoonosis, is prevalent worldwide. Orf is caused by Orf virus (ORFV), which mainly infects sheep/goats and humans. Therefore, effective and safe vaccination strategies for Orf prevention are needed. Although immunization with single-type Orf vaccines has been tested, heterologous prime-boost strategies still need to be studied. In the present study, ORFV B2L and F1L were selected as immunogens, based on which DNA, subunit and adenovirus vaccine candidates were generated. Of note, heterologous immunization strategies using DNA prime-protein boost and DNA prime-adenovirus boost in mice were performed, with single-type vaccines as controls. We have found that the DNA prime-protein boost strategy induces stronger humoral and cellular immune responses than DNA prime-adenovirus boost strategy in mice, which was confirmed by the changes in specific antibodies, lymphocyte proliferation and cytokine expression. Importantly, this observation was also confirmed when these heterologous immunization strategies were performed in sheep. In summary, by comparing the two immune strategies, we found that DNA prime-protein boost strategy can induce a better immune response, which provides a new attempt for exploring Orf immunization strategy.

Heterologous chimpanzee adenovirus vector immunizations for SARS-CoV-2 spike and nucleocapsid protect hamsters against COVID-19.

Available COVID-19 vaccine only provide protection for a limited time due in part to the rapid emergence of viral variants with spike protein mutations, necessitating the generation of new vaccines to combat SARS-CoV-2. Two serologically distinct replication-defective chimpanzee-origin adenovirus (Ad) vectors (AdC) called AdC6 and AdC7 expressing early SARS-CoV-2 isolate spike (S) or nucleocapsid (N) proteins, the latter expressed as a fusion protein within herpes simplex virus glycoprotein D (gD), were tested individually or as a mixture in a hamster COVID-19 SARS-CoV-2 challenge model. The S protein expressing AdC (AdC-S) vectors induced antibodies including those with neutralizing activity that in part cross-reacted with viral variants. Hamsters vaccinated with the AdC-S vectors were protected against serious disease and showed accelerated recovery upon SARS-CoV-2 challenge. Protection was enhanced if AdC-S vectors were given together with the AdC vaccines that expressed the gD N fusion protein (AdC-gDN). In contrast hamsters that just received the AdC-gDN vaccines showed only marginal lessening of symptoms compared to control animals. These results indicate that immune response to the N protein that is less variable than the S protein may potentiate and prolong protection achieved by the currently used S protein based genetic COVID-19 vaccines.

Postvaccination immune-mediated hepatitis: what do we really know?

Tweetable abstract The percentage of patients with immune-mediated vaccine-associated hepatitis is minimal compared with the number of patients vaccinated worldwide.

Informing the design of a whole of life immunisation register for Australia.

INTRODUCTION: In 2016, Australia launched a whole life immunisation register, the Australian Immunisation Register (AIR), building on a universal childhood register established in 1997. Immunisation Information Systems are well established in Europe, the US and elsewhere. However, a national system covering immunisation across the lifespan, with complete capture of the population and satisfactory data quality, is rare. METHODS: A national workshop was convened in 2016 with key stakeholders from the government, new and existing vaccine users, and vaccine providers to review the ideal features of the AIR to ensure optimal effectiveness. This workshop focused on the functionality needed to identify population groups newly included in the register and support the achievement of high immunisation coverage in these groups eligible for National Immunisation Program vaccines. RESULTS: Key recommendations included the need for bidirectional data flow between the AIR and providers; systematic approaches to the capture and recording of accurate and complete data to ascertain important denominators for subpopulations, includingAboriginal and Torres Strait Islander status, medical risk factors, occupation, ethnicity, country of birth, and vaccines given during pregnancy; linkage with other government datasets including notifiable diseases; the capture of adverse events following immunisation; ease of access by patients, providers; and by researchers. CONCLUSIONS: Some recommendations from the workshop have informed the development and future utility of the AIR. Some recommendations from the workshop have been integrated into the current iteration of the AIR, which is more important than ever given the roll-out of COVID-19 vaccines. The accuracy and validity of data have subsequently improved through data entry controls, data integrity checks and reporting requirements. Access to AIR data for research remains protracted and costly, limitingresearch potential.

Egg Yolk Antibody for Passive Immunization: Status, Challenges, and Prospects.

The immunoglobulin Y (IgY) derived from hyperimmune egg yolk is a promising passive immune agent to combat microbial infections in humans and livestock. Numerous studies have been performed to develop specific egg yolk IgY for pathogen control, but with limited success. To date, the efficacy of commercial IgY products, which are all delivered through an oral route, has not been approved or endorsed by any regulatory authorities. Several challenging issues of the IgY-based passive immunization, which were not fully recognized and holistically discussed in previous publications, have impeded the development of effective egg yolk IgY products for humans and animals. This review summarizes major challenges of this technology, including in vivo stability, purification, heterologous immunogenicity, and repertoire diversity of egg yolk IgY. To tackle these challenges, potential solutions, such as encapsulation technologies to stabilize IgY, are discussed. Exploration of this technology to combat the COVID-19 pandemic is also updated in this review.

COVID-19 and Immunization: Reflections and Rationale on Why Child and Adolescent Psychiatry Should Help.

The COVID-19 pandemic has resulted in widespread reflection in medical communities about the role of professional stakeholders in public health interventions. Health professionals, including mental health clinicians, should question how, when, and why they should intervene to address the obstacles and objections to these interventions.

Whole sporozoite immunization with Plasmodium falciparum strain NF135 in a randomized trial.

BACKGROUND: Whole sporozoite immunization under chemoprophylaxis (CPS regime) induces long-lasting sterile homologous protection in the controlled human malaria infection model using Plasmodium falciparum strain NF54. The relative proficiency of liver-stage parasite development may be an important factor determining immunization efficacy. Previous studies show that Plasmodium falciparum strain NF135 produces relatively high numbers of large liver-stage schizonts in vitro. Here, we evaluate this strain for use in CPS immunization regimes. METHODS: In a partially randomized, open-label study conducted at the Radboudumc, Nijmegen, the Netherlands, healthy, malaria-naïve adults were immunized by three rounds of fifteen or five NF135-infected mosquito bites under mefloquine prophylaxis (cohort A) or fifteen NF135-infected mosquito bites and presumptive treatment with artemether/lumefantrine (cohort B). Cohort A participants were exposed to a homologous challenge 19 weeks after immunization. The primary objective of the study was to evaluate the safety and tolerability of CPS immunizations with NF135. RESULTS: Relatively high liver-to-blood inocula were observed during immunization with NF135 in both cohorts. Eighteen of 30 (60%) high-dose participants and 3/10 (30%) low-dose participants experienced grade 3 adverse events 7 to 21 days following their first immunization. All cohort A participants and two participants in cohort B developed breakthrough blood-stage malaria infections during immunizations requiring rescue treatment. The resulting compromised immunizations induced modest sterile protection against homologous challenge in cohort A (5/17; 29%). CONCLUSIONS: These CPS regimes using NF135 were relatively poorly tolerated and frequently required rescue treatment, thereby compromising immunization efficiency and protective efficacy. Consequently, the full potential of NF135 sporozoites for induction of immune protection remains inconclusive. Nonetheless, the high liver-stage burden achieved by this strain highlights it as an interesting potential candidate for novel whole sporozoite immunization approaches. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov under identifier NCT03813108.

Impact assessment of immunization and the COVID-19 pandemic on varicella across Europe using digital epidemiology methods: A descriptive study.

BACKGROUND: Varicella is usually a mild disease in children but may be life-threatening, especially in adolescents and adults. Infection control measures implemented during the Coronavirus Disease 2019 (COVID-19) pandemic may have suppressed varicella transmission, potentially creating an 'immunity debt', particularly in countries without universal varicella vaccination. OBJECTIVES: To assess trends in Google search engine queries for varicella keywords as a proxy for varicella infection rates and to evaluate the effect of universal varicella vaccination on these trends. A further objective was to assess the impact of the COVID-19 pandemic on varicella keyword search query trends in countries with and without universal varicella vaccination. METHODS: This study used the keyword research tool, Google Trends, to evaluate trends in time series of the relative search query popularity of language-specific varicella keywords in 28 European countries from January 2015 through December 2021. The Google Ads Keyword Planner tool was used to evaluate absolute search volumes from March 2018 through December 2021. RESULTS: The relative search query popularity of varicella keywords displayed marked seasonal variation. In all 28 countries, the relative search query popularity of varicella keywords declined after the start of the COVID-19 pandemic (March 2020), compared with pre-pandemic levels (range, -18% to -70%). From April 2020 to July 2021, a period of intense COVID-19 transmission and infection control, absolute search volumes for varicella keywords were lower than pre-pandemic levels but rebounded after July 2021, when infection control measures were relaxed. CONCLUSION: This evaluation of search query trends demonstrated that search query data could be used as a proxy for trends in varicella infection rates and revealed that transmission of varicella may have been suppressed during the COVID-19 pandemic. Consideration should be given to using search query data to better understand the burden of varicella, particularly in countries where surveillance systems are inadequate.

DNA immunization with in silico predicted T-cell epitopes protects against lethal SARS-CoV-2 infection in K18-hACE2 mice.

The global SARS-CoV-2 pandemic caused significant social and economic disruption worldwide, despite highly effective vaccines being developed at an unprecedented speed. Because the first licensed vaccines target only single B-cell antigens, antigenic drift could lead to loss of efficacy against emerging SARS-CoV-2 variants. Improving B-cell vaccines by including multiple T-cell epitopes could solve this problem. Here, we show that in silico predicted MHC class I/II ligands induce robust T-cell responses and protect against severe disease in genetically modified K18-hACE2/BL6 mice susceptible to SARS-CoV-2 infection.

Evaluation of mortality risk after COVID-19 vaccination, Utah 2021.

INTRODUCTION: In order to evaluate trends in death after COVID-19 vaccination we analyzed the timing of death relative to vaccination date and the causes of death in vaccinated Utahns in 2021. METHODS: We matched people in the Utah immunization registry with documented COVID-19 vaccinations between December 18, 2020 and December 31, 2021 to Utah's 2021 vital statistics death records. Vaccinated people were categorized as having one, two, or ≥ three COVID-19 vaccine doses in a time-updated metric. We examined crude mortality rates by dosing groups in two-week intervals for all deaths, and by COVID-19 versus non-COVID-19 causes, within the 44 weeks following receipt of the most recent vaccine. RESULTS: We identified 2,072,908 individuals who received at least one dose of COVID-19 vaccine of whom 10,997 died in 2021. Only 17.5 % of the total vaccinated population was age 65+, while 80.9 % of those who died were over 65. In the four weeks following the first or second vaccination, all-cause mortality was low and then stabilized for the remainder of the evaluation period at a bi-weekly average of 33.0 and 39.0 deaths/100,000 people for one and two doses, respectively. Typical seasonal variation in death was observed among those with two doses. Small sample size precluded analysis of those with ≥ three doses, but trends were similar. CONCLUSIONS: Mortality rates in the 44 weeks following the COVID-19 vaccination did not show trends suggesting an increase in mortality related to COVID-19 vaccination, reinforcing the safety of COVID-19 vaccines. This represents an accessible approach for local evaluation.

Immunisation with purified Coxiella burnetii phase I lipopolysaccharide confers partial protection in mice independently of co-administered adenovirus vectored vaccines.

Q fever is a highly infectious zoonosis caused by the Gram-negative bacterium Coxiella burnetii. The worldwide distribution of Q fever suggests a need for vaccines that are more efficacious, affordable, and does not induce severe adverse reactions in vaccine recipients with pre-existing immunity against Q fever. Potential Q fever vaccine antigens include lipopolysaccharide (LPS) and several C. burnetii surface proteins. Antibodies elicited by purified C. burnetii lipopolysaccharide (LPS) correlate with protection against Q fever, while antigens encoded by adenoviral vectored vaccines can induce cellular immune responses which aid clearing of intracellular pathogens. In the present study, the immunogenicity and the protection induced by adenoviral vectored constructs formulated with the addition of LPS were assessed. Multiple vaccine constructs encoding single or fusion antigens from C. burnetii were synthesised. The adenoviral vectored vaccine constructs alone elicited strong cellular immunity, but this response was not correlative with protection in mice. However, vaccination with LPS was significantly associated with lower weight loss post-bacterial challenge independent of co-administration with adenoviral vaccine constructs, supporting further vaccine development based on LPS.