Vaccines

Background: Considering the indeterminate effects following the administration of three doses of the SARS-CoV-2 vaccine to patients under dialysis, the present study aimed to evaluate the immunogenicity rates of patients who received the three-dose vaccine. Methods: MEDLINE, Web of Science, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register for Controlled Trials were searched to select the relevant literature to perform the present review. We included randomized controlled trials, non-randomized trials, prospective, observational cohort, and case-control studies to assess the humoral and cellular immune responses following the administration of the three-dose SARS-CoV-2 vaccine to patients receiving dialysis. Results: Overall, 38 studies are included in the meta-analysis presented in this paper. For patients on dialysis, the overall humoral antibody response rate is 97% following three doses of mRNA or viral vector vaccines and 100% following four doses of the SARS-CoV-2 vaccine. A subgroup analysis shows that the antibody response rate is 96% for patients on hemodialysis (HD) and 100% for those receiving peritoneal dialysis (PD). The antibody response rate in the different immunogen-vaccinated groups tends to be higher than that in the same immunogen-vaccinated group (99% vs. 96%). For those who exhibit no response following two doses of the vaccine, the third and fourth doses can elevate the antibody response rate to 81%, and that number for low responders increases to 96%. However, the pooled results obtained from the relatively few trials conducted indicate that the positive T-cell response rate only increases to 59% following three doses of the vaccine. The antibody response rate is not different between dialysis and non-dialysis groups (relative risk = 0.95, 95% CI 0.90–1.02) following three doses of the vaccine. The relative risks for a SARS-CoV-2 breakthrough infection, all-cause mortality, and hospital admissions are 0.59 (95%CI 0.30–1.04), 0.63 (95%CI 0.35–1.12), and 0.53 (95%CI 0.37–0.74), respectively, when comparing three doses with two doses of the vaccine administered to the dialysis population. Conclusions: The third or fourth dose of the SARS-CoV-2 vaccine significantly increases the immunogenicity rates in dialysis patients, and this beneficial effect does not vary with the type of vaccine (the same or different immunogen vaccination), dialysis modality (HD or PD), or previous low response following the administration two doses of the vaccine. We believe that healthcare workers should encourage patients receiving dialysis to receive a third or fourth vaccine dose to strengthen their immunity against SARS-CoV-2. Full article

Background: From May to December 2021, Bangladesh experienced a major surge in the Delta variant of SARS-CoV-2. The earlier rollout of several vaccines offered the opportunity to evaluate vaccine effectiveness against this variant. Methods: A prospective, test-negative case-control study was conducted in five large hospitals in Dhaka between September and December 2021. The subjects were patients of at least 18 years of age who presented themselves for care, suffering COVID-like symptoms of less than 10 days’ duration. The cases had PCR-confirmed infections with SARS-CoV-2, and up to 4 PCR test-negative controls were matched to each case, according to hospital, date of presentation, and age. Vaccine protection was assessed as being the association between the receipt of a complete course of vaccine and the occurrence of SARS-CoV-2 disease, with symptoms beginning at least 14 days after the final vaccine dose. Results: In total, 313 cases were matched to 1,196 controls. The genotyping of case isolates revealed 99.6% to be the Delta variant. Receipt of any vaccine was associated with 12% (95% CI: −21 to 37, p = 0.423) protection against all episodes of SARS-CoV-2. Among the three vaccines for which protection was evaluable (Moderna (mRNA-1273); Sinopharm (Vero Cell-Inactivated); Serum Institute of India (ChAdOx1 nCoV-19)), only the Moderna vaccine was associated with significant protection (64%; 95% CI: 10 to 86, p = 0.029). Protection by the receipt of any vaccine against severe disease was 85% (95% CI: 27 to 97, p = 0.019), with protection estimates of 75% to 100% for the three vaccines. Conclusions: Vaccine protection against COVID-19 disease of any severity caused by the Delta variant was modest in magnitude and significant for only one of the three evaluable vaccines. In contrast, protection against severe disease was high in magnitude and consistent for all three vaccines. Because our findings are not in complete accord with evaluations of the same vaccines in more affluent settings, our study underscores the need for country-level COVID-19 vaccine evaluations in developing countries. Full article

(a) Background: Omalizumab is an anti-IgE humanized monoclonal antibody marketed in China for the conventional treatment of poorly controlled moderate-to-severe allergic asthma. Numerous clinical trials have demonstrated the effectiveness of omalizumab, but the data from studies in actual clinical treatment are still relatively limited. (b) Methods: Thirty-two patients with moderate-to-severe allergic asthma treated with omalizumab on the basis of ICS-LABA (inhaled corticosteroids/long-acting beta2-agonist) were selected. Clinical characteristics before and after treatment were collected to analyze the relationship between changes in serum total IgE levels and peripheral blood EOS (eosinophil) levels, FEV1 (forced expiratory volume in 1 second), PEF (peak expiratory flow), OCS (oral glucocorticoid) dosage, ATC (asthma control test) score, and the number of acute exacerbations and the treatment response, in order to observe the efficacy of omalizumab in addition to primary therapy, and to investigate whether baseline clinical characteristics such as serum total IgE and EOS levels could predict a treatment response. (c) Results: Using the ACT score as an evaluation, 68.75% of patients benefited from omalizumab treatment at the end of 16 weeks. The response group has a reduction in OCS dosage (p-values of 0.026 and 0.039), a significant reduction in ACT scores (both p < 0.001), and a reduction in the number of acute exacerbations (p = 0.034 and 0.025, respectively) after omalizumab treatment. The binary logistics analysis of factors affecting the effectiveness of omalizumab in the treatment of allergic asthma were total serum IgE and the presence of comorbidities (p-values of 0.039 and 0.046, respectively). (d) Conclusions: Combining omalizumab with ICS-LABA for 16 weeks significantly improves asthma symptoms in Chinese adults and can be used as an add-on treatment. In addition, high serum IgE levels and the presence of comorbidities were predictors of its therapeutic efficacy. Full article

As the anti-vaccination movement is spreading around the world. This paper addresses the ever more urgent need for health professionals, communicators and policy-makers to grasp the nature of vaccine mis/disinformation on social media is more urgent than ever. A one-by-one coding of 4511 vaccine-related tweets posted from the UK in 2019 resulted in 334 anti-vaccine tweets. Our analysis shows that (a) anti-vaccine tweeters are quite active and widely networked users on their own; (b) anti-vaccine messages tend to focus on the “harmful” nature of vaccination, based mostly on personal experience, values and beliefs rather than hard facts; (c) anonymity does not make a difference to the types of posted anti-vaccine content, but does so in terms of the volume of such content. Communication initiatives against anti-vaccination should (a) work closely with technological platforms to tackle anonymous anti-vaccine tweets; (b) focus efforts on mis/disinformation in three major arears (in order of importance): the medical nature of vaccines, the belief that vaccination is a tool of manipulation and control for money and power, and the “freedom of health choice” discourse against mandatory vaccination; and (c) go beyond common factual measures—such as detecting, labelling or removing fake news—to address emotions induced by personal memories, values and beliefs. Full article

The current influenza vaccines only confer protection against the circulating influenza subtypes, therefore universal vaccines are needed to prevent upcoming influenza outbreaks caused by emerging influenza subtypes. The extracellular domain of influenza A M2 protein (M2e) is highly conserved among different subtypes of influenza A viruses, and it is able to elicit protective immunity against the viruses. The influenza nucleoprotein (NP) was used to display the M2e in this study due to its promising T-cell response and adjuvanticity. The M2e gene was fused to the 5′-end of the NP gene and then cloned into pRSET B vector. The DNA sequencing analysis revealed six point mutations in the M2e-NP fusion gene, including one mutation in the M2e peptide and five mutations in the NP. The mutations were reverted using PCR site-directed mutagenesis. The recombinant plasmids (pRSET B-M2e-NP and pRSET B-mM2e-NP) were introduced into Escherichia coli (E. coli) BL21 (DE3) for protein expression. The mutated and non-mutated proteins were subsequently expressed and named mM2e-NP and M2e-NP, respectively. The expression of mM2e-NP and M2e-NP was not affected by the mutations. The binding of anti-M2e antibody to the purified native mM2e-NP and M2e-NP also remained active. However, when the anti-NP antibody was tested, the signal produced by mM2e-NP was very weak. The results implied that the amino acid changes in the NP had adversely impacted on the conformation of mM2e-NP and subsequently affected the antibody binding. In light of the remarkable antibody binding to the M2e-NP fusion protein, this study highly recommends the potential of M2e-NP as a universal influenza vaccine candidate. Full article

This article provides a systematic assessment of the efficacy, risks, and methodological quality of evidence from five major publicly available vaccine trials. Results from Pfizer-BioNTech mRNA, Moderna-US NIH mRN-1273, AstraZeneca-Oxford ChAdOx1 nCov-19, Gamaleya GamCovidVac (Sputnik V), and Ad26.COV2.S Johnson & Johnson vaccines were included. Extracted benefits and risks data from each trial were summarized using the GRADE approach denoting the overall certainty of evidence along with relative and absolute effects. Relative risk reduction across all five vaccine trials ranged from 45% to 96%. Absolute risk reduction in symptomatic COVID-19 ranged from 6 to 17 per 1000 across trials. None of the vaccines were associated with a significant increase in serious adverse events compared to placebo. The overall certainty of evidence varied from low to moderate. All five vaccines are effective and safe, but suggest room for improvement in the conduct of large-scale vaccine trials. Certainty of evidence was downrated due to risk of bias, which can be mitigated by improving transparency and thoroughness in conduct and reporting of outcomes. Full article

Cervical cancer is the most common gynecological malignant tumor worldwide, and it remains a major health problem among women, especially in developing countries. Despite the significant research efforts employed for tumor prevention, cervical cancer ranks as the leading cause of cancer death. Human papillomavirus (HPV) is the most important risk factor for cervical cancer. Cervical cancer is a preventable disease, for which early detection could increase survival rates. Immunotherapies represent a promising approach in the treatment of cancer, and several potential candidates are in clinical trials, while some are available in the market. However, equal access to available HPV vaccines is limited due to their high cost, which remains a global challenge for cervical cancer prevention. The implementation of screening programs, disease control systems, and medical advancement in developed countries reduce the serious complications associated with the disease somewhat; however, the incidence and prevalence of cervical cancer in low-income and middle-income countries continues to gradually increase, making it the leading cause of mortality, largely due to the unaffordable and inaccessible anti-cancer therapeutic options. In recent years, plants have been considered as a cost-effective production system for the development of vaccines, therapeutics, and other biopharmaceuticals. Several proof-of-concept studies showed the possibility of producing recombinant biopharmaceuticals for cancer immunotherapy in a plant platform. This review summarizes the current knowledge and therapeutic options for the prevention of cervical cancer and discusses the potential of the plant expression platform to produce affordable HPV vaccines. Full article

The host immune response to SARS-CoV-2 appears to play a critical role in disease pathogenesis and clinical manifestations in severe COVID-19 cases. Until now, the importance of developing a neutralizing antibody response in the acute phase and its relationship with progression to severe disease or fatal outcome among hospitalized patients remains unclear. In this study, we aim to characterize and compare longitudinally the primary humoral immune host response in the early stages of the disease, looking for an association between neutralization, antibody titers, infective viral lineage, and the clinical outcome in hospitalized and non-hospitalized patients. A total of 111 patients admitted at INER from November 2021 to June 2022 were included. We found that patients with negative or low neutralization showed a significant reduction in survival probability compared to patients with medium or high neutralization. We observed a significant decrease in the median of neutralization in patients infected with viral variants with changes in RBD of the spike protein. Our results suggest that developing an early and robust neutralizing response against SARS-CoV-2 may increase survival probability in critical patients. Full article

Despite the negative impact of viral hemorrhagic septicemia (VHS) and infectious hematopoietic necrosis (IHN) on European rainbow trout farming, no vaccines are commercially available in Europe. DNA vaccines are protective under experimental conditions, but testing under intensive farming conditions remains uninvestigated. Two DNA vaccines encoding the glycoproteins (G) of recent Italian VHSV and IHNV isolates were developed and tested for potency and safety under experimental conditions. Subsequently, a field vaccination trial was initiated at a disease-free hatchery. The fish were injected intramuscularly with either the VHS DNA vaccine or with a mix of VHS and IHN DNA vaccines at a dose of 1 µg/vaccine/fish, or with PBS. At 60 days post-vaccination, fish were moved to a VHSV and IHNV infected facility. Mortality started 7 days later, initially due to VHS. After 3 months, IHN became the dominant cause of disease. Accordingly, both DNA vaccinated groups displayed lower losses compared to the PBS group during the first three months, while the VHS/IHN vaccinated group subsequently had the lowest mortality. A later outbreak of ERM caused equal disease in all groups. The trial confirmed the DNA vaccines to be safe and efficient in reducing the impact of VHS and IHN in farmed rainbow trout. Full article

This is a monocentric and cross-sectional study conducted at the COVID-19 Division of the Obstetrical and Gynecological Unit and Intensive Care Units (ICUs) of Policlinico di Bari, in Bari, Italy, between September 2020 and April 2022. This study aimed to identify the prevalence of severe-critical COVID-19 illness requiring access to the Intensive Care Unit (ICU) among 287 pregnant patients, and possible correlations between the SARS-CoV-2 variants, the specific pandemic wave (dominated by wild, Alpha, Delta, and Omicron strains), and severe-critical adverse maternal outcomes. The prevalence of severe-critical COVID-19 illness was 2.8% (8/287), reaching 4.9% (8/163) excluding the 4th wave (Omicron dominant). The Delta variant determined the highest risk ratio and odds for access to the ICU due to severe-critical COVID-19-related symptoms compared to the other variants (wild, Alpha, Omicron). During the third wave (Delta), the ICU cases underwent a higher rate of hyperimmune plasma infusion (75%), antibiotic therapy (75%), and remdesivir (33%); all of the patients were intubated. During the Omicron wave, the patients were asymptomatic or with few symptoms: most of them (70%) were vaccinated with a median of two doses. The maternal outcome worsened in the case of Alpha and, especially, Delta variants for severe-critical COVID-19-related symptoms and ICU access. Full article

Infections contracted during healthcare delivery in a hospital or ambulatory setting are collectively referred to as healthcare-associated infections (HAIs). Healthcare workers and patients alike are vulnerable to serious problems as a result of the risk of HAIs. In the healthcare system, HAIs are considered among the most common and serious health problems. However, the occurrence of HAIs differs between different types of clinical departments within the hospital. Recently, the risk of HAIs has been increasing in radiology departments globally due to the central role of radiology in guiding clinical decisions for the diagnosis, treatment, and monitoring of different diseases from almost all medical specialties. The radiology department is particularly vulnerable to HAIs because it serves as a transit hub for infected patients, non-infected patients, and healthcare workers. Furthermore, as the number of patients referred to radiology and the length of patient contact time has increased, thanks to modern imaging techniques such as computed tomography and magnetic resonance imaging, the risk of HAIs has also increased significantly. With the increasing use of interventional radiological procedures, patients and healthcare workers face a potentially greater risk of contracting HAIs due to the invasive nature of such procedures. Although not exhaustive, we attempted through a literature search to provide a general overview of infection prevention and control practices, address HAIs in the radiology departments, and highlight the challenges and measures taken to control infection transmission in the radiology departments. Full article

As a developmental toxicant, Zika virus (ZIKV) attacks both the growing nervous system, causing congenital Zika syndrome, and the placenta, resulting in pathological changes and associated adverse fetal outcomes. There are no vaccines, antibodies, or other treatments for ZIKV, despite the potential for its re-emergence. Multiple studies have highlighted the risk of antibodies for enhancing ZIKV infection, including during pregnancy, but the mechanisms for such effects are not fully understood. We have focused on the ability of the neonatal Fc receptor (FcRn) to interact with ZIKV in the presence and absence of relevant antibodies. We found that ZIKV replication was higher in Marvin Darby Canine Kidney (MDCK) cells that overexpress FcRn compared to those that do not, and knocking down FcRn decreased ZIKV RNA production. In the placenta trophoblast BeWo cell line, ZIKV infection itself downregulated FcRn at the mRNA and protein levels. Addition of anti-ZIKV antibodies to MDCK/FcRn cells resulted in non-monotonous neutralization curves with neutralization attenuation and even enhancement of infection at higher concentrations. Non-monotonous neutralization was also seen in BeWo cells at intermediate antibody concentrations. Our studies highlight the underappreciated role FcRn plays in ZIKV infection and may have implications for anti-ZIKV prophylaxis and therapy in pregnant women. Full article

Healthcare workers (HCWs) are at increased risk of Sars-CoV-2 infection because of their occupational exposure. Moreover, they can be a vehicle for the virus transmission among patients. The vaccination of healthcare personnel against COVID-19 is crucial in fighting the spread of SARS-CoV-2 infection, together with strict sanitary procedures that aim to limit the risk of contagion. Unfortunately, even if COVID-19 vaccination has been proved one of the most effective tools for protecting against COVID-19, many healthcare professionals are not yet vaccinated. The aim of the current review is to contribute to identifying an effective strategy for COVID-19 prevention especially among non-vaccinated HCWs. In this review, we collected the most recent and relevant findings from literature on the protection of unvaccinated HCWs, identifying three types of measures as principal actions to protect those operators: addressing vaccine hesitancy, improving non-pharmaceutical interventions and promoting actions at personal level (respiratory hygiene, hand hygiene and use of PPE). All these interventions are very effective in preventing contagion, if well respected and conducted; nevertheless, it is essential to promote vaccination, as it is the most effective measure. Full article

Vaccines are essential to ensuring a nation’s health, wellbeing and prosperity. After the coronavirus pandemic commenced, the Australian Government introduced social restrictions to constrain virus transmission, seeing significant economic impacts. Reflecting the extraordinary circumstances, subsequent vaccination rollout forwent usual health technology assessment (HTA) processes, facilitating restrictions removal and leading to societal and economic recovery. However, in ‘usual’ circumstances, HTA may not consider such broader effects of vaccines, making it challenging for them to achieve timely funding. We used detailed modelling to compare economic impacts under continued lockdowns against population-wide vaccination rollout between January 2020 and June 2023 and examined global HTA vaccine evaluation methodologies and efforts to develop broader valuation approaches. Australian gross domestic product reduces by approximately AUD 395 billion with lockdowns. With vaccination rollout, this effect is approximately AUD 214bn, a positive incremental impact of AUD 181bn. Vaccination contributes to large estimated positive effects for tourism (AUD 28bn) and education (AUD 26bn) exports, employment (142,000 jobs) and government finances (AUD 259bn). Conversely, global HTA methods generally only consider direct patient health outcomes and healthcare system-related costs, with broader effects usually not impacting funding decisions. Our results suggest that recent efforts to propose broader HTA valuation frameworks warrant further policy consideration. Full article

Background: in this report, we describe the case of an 83-year-old woman vaccinated with ChadOx1 nCoV-19 who developed a so-called vaccine-induced thrombosis with thrombocytopenia syndrome and who did not develop any antibodies against the spike protein of SARS-CoV-2 at 30 days following the administration of her first dose of ChadOx1 nCoV-19. Experimental section: two serum samples from the patient and 5 serum samples from 5 control individuals having received the two-dose regimen vaccination with ChadOx1 nCoV-19 were evaluated. In order to investigate the lack of response to the vaccination, a cell model was developed. This model permits to evaluate the interaction between responsive cells (A549) possessing the Coxsackievirus and Adenovirus Receptor (CAR), a defined concentration of ChadOx1 nCoV-19 and serial dilution of the patient or the control serum. The aim was to assess the impact of these sera on the production of the spike (S) protein induced by the transfection of the genetic material of ChadOx1 nCoV-19 into the A549 cells. The S protein is measured in the supernatant using an ELISA technique. Results: interestingly, the serum from the patient who developed the vaccine-induced thrombosis with thrombocytopenia syndrome impaired the production of S protein by the A549 cells transfected with ChadOx1 nCoV-19. This was not observed with the controls who did not interfere with the transfection of ChadOx1 nCoV-19 into A549 cells since the S protein is retrieved in the supernatant fraction. Conclusion: based on the data coming from the clinical and the cell model information, we found a possible explanation on the absence of antibody response in our patient. She has, or has developed, characteristics that prevent the production of the S protein in contrast to control subjects. We were not able to investigate the entire mechanism behind this resistance which deserve further investigations. A link between this resistance and the development of the thrombosis with thrombocytopenia syndrome following vaccination with ChadOx1 nCoV-19 cannot be excluded. Full article

Mass vaccination against COVID-19 is necessary to control the pandemic. COVID-19 vaccines are now recommended during pregnancy to prevent the disease. A systematic review of the literature in the electronic databases PubMed and EMBASE was performed and we aimed to investigate the attitude of documents towards COVID-19 vaccination and the prognostic factors of vaccination hesitation. A meta-analysis was also conducted to estimate the overall percentage of pregnant women who were willing to be vaccinated or had been vaccinated against COVID-19. A total of 18 studies were included in the review and meta-analysis. The acceptance rate of vaccination against COVID-19 among pregnant women ranged from 17.6% to 84.5%. The pooled proportion of acceptance of vaccination against COVID-19 in pregnant women was 0.53 (95% CI: 0.44–0.61). Predictors of acceptance of COVID-19 vaccination were older age, White race, occupational status, higher level of education, comorbidities, third trimester of pregnancy, influenza vaccination, knowledge about COVID-19, and confidence that vaccines for COVID-19 are safe and effective. The prevalence of COVID-19 vaccination in pregnant women is low. Targeted information campaigns are needed to increase vaccine education in this population. Full article

Multiple vaccines may prevent meningitis and encephalitis (M/E). In China, the meningococcal vaccine and Japanese encephalitis vaccine (JEV) have been included in the expanded program of immunization (EPI). The pneumococcal vaccine, Haemophilus influenzae type b (Hib) vaccine, rotavirus vaccine, and enterovirus 71 (EV-71) vaccine are non-EPI vaccines and are self-paid. We aim to investigate the uptake of these M/E vaccines in children and the related knowledge and health beliefs among family caregivers. A total of 1011 family caregivers with children aged 1–6 years in Shanghai, China were included in the study. The uptake of the pneumococcal vaccine, Hib-containing vaccine, rotavirus vaccine, and EV-71 vaccine remained at 44.0–48.1% in children, compared with the higher uptake of the meningococcal vaccine (88.8%) and JEV (87.1%). Moreover, family caregivers had limited knowledge on the M/E pathogens and possible vaccines. Their health beliefs were moderate to high. Then, a health belief model (HBM) and a structural equation model were established. The uptake of four non-EPI vaccines was significantly influenced by family income (β = 0.159), knowledge (β = 0.354), self-efficacy (β = 0.584), and perceived susceptibility (β = 0.212) within an HBM. Therefore, it warrants further improving the uptake rate for these non-EPI vaccines to prevent potential M/E in children. A specific health promotion may empower the caregivers’ decision-making on childhood vaccination. Full article

Background: Cameroon’s suboptimal access to childhood vaccinations poses a significant challenge to achieving the Immunization Agenda 2030 goal—ranking among the top 15 countries with a high proportion of zero-dose (unvaccinated) children worldwide. There are clusters of zero-dose children in pockets of communities that traditionally miss essential healthcare services, including vaccination. The Manoka Health District (MHD) is home to such settlements with consistently low vaccination coverages (DPT-HepB-Hib-1: 19.8% in 2021) and frequent outbreaks of vaccine-preventable diseases (VPD). Therefore, the absence of literature on zero-dose children in this context was a clarion call to characterize zero-dose children in fragile settings to inform policy and intervention design. Methodology: This cross-sectional analytical study involved 278 children, 0–24 months of age, selected from a 2020 door-to-door survey conducted in the two most populous health areas in an archipelago rural district, MHD (Cap-Cameroon and Toube). We used R Statistical Software (v4.1.2; R Core Team 2021) to run a multivariable logistic regression to determine zero-dose associated factors. Results: The survey revealed a zero-dose proportion of 91.7% (255) in MHD. Children who were delivered in health facilities were less likely to be zero-dose than those born at home (AOR: 0.07, 95% CI: 0.02–0.30, p = 0.0003). Compared to children born of Christian mothers, children born to minority non-Christian mothers had higher odds of being zero-dose (AOR: 6.55, 95% CI: 1.04–41.25, p = 0.0453). Children born to fathers who are immigrants were more likely to be zero-dose children than Cameroonians (AOR: 2.60, 95% CI = 0.65–10.35, p = 0.0016). Younger children were likely to be unvaccinated compared to older peers (AOR: 0.90, 95% CI: 0.82–1.00, p = 0.0401). Conclusions: In the spirit of “leaving no child behind,” the study highlights the need to develop context-specific approaches that consider minority religious groups, immigrants, and younger children, including newborns, often missed during vaccination campaigns and outreaches Full article