Vaccines, Volume 12, Issue 5 (May 2024) – 51 articles

Multiple factors may influence parental vaccine hesitancy towards pediatric COVID-19 vaccines and routine childhood immunizations (RCIs). Using the United States National Immunization Survey—Child COVID Module data collected from parents/guardians of children aged 5–11 years, this cross-sectional study (1) identified the trends and prevalence estimates of parental hesitancy towards pediatric COVID-19 vaccines and RCIs, (2) examined the relationship between hesitancy towards pediatric COVID-19 vaccines and RCIs, and (3) assessed trends in parental hesitancy towards RCIs by sociodemographic characteristics and behavioral and social drivers of COVID-19 vaccination. From November 2021 to July 2022, 54,329 parents or guardians were interviewed. During this 9-month period, the proportion of parents hesitant about pediatric COVID-19 vaccines increased by 15.8 percentage points (24.8% to 40.6%). Additionally, the proportion of parents who reported RCIs hesitancy increased by 4.7 percentage points from November 2021 to May 2022 but returned to baseline by July 2022. Over nine months, parents’ concerns about pediatric COVID-19 infections declined; however, parents were increasingly worried about pediatric COVID-19 vaccine safety and overall importance. Furthermore, pediatric COVID-19 vaccine hesitancy was more prevalent among parents of children who were White (43.2%) versus Black (29.3%) or Hispanic (26.9%) and those residing in rural (51.3%) compared to urban (28.9%) areas. In contrast, RCIs hesitancy was higher among parents of children who were Black (32.0%) versus Hispanic (24.5%) or White (23.6%). Pediatric COVID-19 vaccine hesitancy was 2–6 times as prevalent among parents who were RCIs hesitant compared to those who were RCIs non-hesitant. This positive correlation between parental hesitancy towards pediatric COVID-19 vaccines and RCIs was observed for all demographic and psychosocial factors for unadjusted and adjusted prevalence ratios. Parent–provider interactions should increase vaccine confidence, shape social norms, and facilitate behavior change to promote pediatric vaccination rates. Full article

COVID-19 vaccines represent effective public health measures in contrasting the pandemic worldwide. However, protection at the individual-level, which is of crucial importance from an occupational health perspective, is commonly assessed by a serological correlate of protection (CoP) for SARS-CoV-2, which has not yet been determined. The emergence of variants of concern (VOCs) that have shown high rates of breakthrough infections has further complicated the understanding of immune protection against infection. To define a potential serological correlate of protection induced by the COVID-19 vaccination, a systematic review and meta-analysis was performed to summarize the evidence concerning the binding antibody concentration corresponding to a protective effect. Eighteen and four studies were included in the qualitative and quantitative analyses, respectively. The protection against infection was shown for anti-receptor-binding domain (RBD) titers ranging from 154 to 168.2 binding antibody units (BAU)/mL during the pre-Omicron period, while ranging from 1235 to 3035 BAU/mL in the Omicron period. Pooling the results from the studies concerning anti-RBD and anti-Spike antibody titer, we found a mean of 1341.5 BAU/mL and 1400.1 BAU/mL, respectively. These findings suggest that although a fixed serological threshold corresponding to protection against different SARS-CoV-2 variants is not yet definable, higher binding antibody concentrations are associated with increased protective effects. Full article

Since the beginning of the COVID-19 pandemic, different viral vector-based and mRNA vaccines directed against the SARS-CoV-2 “S” spike glycoprotein have been developed and have shown a good profile in terms of safety and efficacy. Nevertheless, an unbiased comparison of vaccination efficiency, including post-vaccination neutralizing activity, between the different vaccines remains largely unavailable. This study aimed to compare the efficacy of one mRNA (BNT162b2) and two non-replicating adenoviral vector vaccines (ChAdOx1 nCoV-19 and Sputnik V) in a cohort of 1120 vaccinated Palestinian individuals who received vaccines on an availability basis and which displayed a unique diversity of genetic characteristics. We assessed the level of anti-S antibodies and further determined the antibody neutralizing activity in 261 of those individuals vaccinated with BNT162b2a (121), ChAdOx1 (72) or Sputnik V (68). Our results showed no significant difference in the distribution of serum-neutralizing activity or S-antibody serum levels for the three groups of vaccines, proving equivalence in efficacy for the three vaccines under real-life conditions. In addition, none of the eight demographic parameters tested had an influence on vaccination efficacy. Regardless of the vaccine type, the vaccination campaign ultimately played a pivotal role in significantly reducing the morbidity and mortality associated with COVID-19 in Palestine. Full article

Viral vector vaccines represent a substantial advancement in immunization technology, offering numerous benefits over traditional vaccine modalities. The Orf virus (ORFV) strain D1701-VrV is a particularly promising candidate for vaccine development due to its distinctive attributes, such as a good safety profile, the ability to elicit both humoral and cellular immunity, and its favorable genetic and thermal stability. Despite ORFV’s theoretical safety advantages, such as its narrow host range and limited systemic spread post-inoculation, a critical gap persists between these theoretical benefits and the empirical evidence regarding its in vivo safety profile. This discrepancy underscores the need for comprehensive preclinical validations to bridge this knowledge gap, especially considering ORFV’s use in humans. Our research introduces Prime-2-CoV, an innovative ORFV-based vaccine candidate against COVID-19, designed to elicit a robust immune response by expressing SARS-CoV-2 Nucleocapsid and Spike proteins. Currently under clinical trials, Prime-2-CoV marks the inaugural application of ORFV in human subjects. Addressing the aforementioned safety concerns, our extensive preclinical evaluation, including an environmental risk assessment (ERA) and detailed pharmacokinetic studies in rats and immunocompromised NOG mice, demonstrates Prime-2-CoV’s favorable pharmacokinetic profile, negligible environmental impact, and minimal ERA risks. These findings not only affirm the vaccine’s safety and efficacy but also pioneer the use of ORFV-based therapeutics, highlighting its potential for wider therapeutic applications. Full article

The emergence of rapidly spreading variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) poses a major challenge to vaccines’ protective efficacy. Intramuscular (IM) vaccine administration induces short-lived immunity but does not prevent infection and transmission. New vaccination strategies are needed to extend the longevity of vaccine protection, induce mucosal and systemic immunity and prevent viral transmission. The intranasal (IN) administration of the VSV–ΔG–spike vaccine candidate directly to mucosal surfaces yielded superior mucosal and systemic immunity at lower vaccine doses. Compared to IM vaccination in the K18–hACE2 model, IN vaccination preferentially induced mucosal IgA and T-cells, reduced the viral load at the site of infection, and ameliorated disease-associated brain gene expression. IN vaccination was protective even one year after administration. As most of the world population has been vaccinated by IM injection, we demonstrate the potential of a heterologous IM + IN vaccination regimen to induce mucosal immunity while maintaining systemic immunity. Furthermore, the IM + IN regimen prevented virus transmission in a golden Syrian hamster co-caging model. Taken together, we show that IN vaccination with VSV–ΔG–spike, either as a homologous IN + IN regimen or as a boost following IM vaccination, has a favorable potential over IM vaccination in inducing efficient mucosal immunity, long-term protection and preventing virus transmission. Full article

Prime-2-CoV_Beta is a novel Orf virus (ORFV)-based COVID-19 vaccine candidate expressing both the nucleocapsid and spike proteins of SARS-CoV-2 with the receptor-binding domain (RBD) of the Beta strain. This candidate was shown to be safe and immunogenic in a first-in-human Phase I clinical trial. With the shift in the immune landscape toward the Omicron variant and the widespread vaccine- and/or infection-derived immunity, further pre-clinical research was needed to characterize Prime-2-CoV. Here, we quantified the humoral and cellular response to Prime-2-CoV_Beta in pre-immunized mice and compared the protective efficacy of mono- and bivalent variant-based Prime-2-CoV vaccine candidates in hamsters. Prime-2-CoV_Beta induced robust humoral and cellular immune responses in naïve animals but did not further boost antibody titers in the tested setting when given as repeat booster at short interval. We furthermore showed that Prime-2-CoV_Beta-based mono- and bivalent immunization strategies produced comparable immunogenicity and protection from infection. Our results highlight the potential of the Orf virus as a vaccine platform against SARS-CoV-2 and potentially other infectious viruses. Full article

Background: Cervical cancer, caused by human papillomavirus (HPV) infection, is the second-largest cancer killer of women in low- and middle-income countries. The brunt of the global burden is borne predominantly in Sub-Saharan Africa. In 2020 alone, 70,000 of the 100,000 infected women in Africa died from it, thereby making up 21% of global cervical cancer mortality. The introduction of the HPV vaccine into the National Immunization Program was expected to change the trajectory. However, uptake of the vaccination has been poor, especially for the second dose. Only about half of the countries in Africa currently provide the vaccine. Without urgent intervention, the 2030 global cervical cancer elimination targets will be undermined. The study aims to understand the key challenges facing the HPV vaccine and to develop a roadmap to accelerate the uptake. Method: Fourteen countries were purposively included using a cohort design methodology and the investigation spanned March–July 2023. The Africa region was stratified into three focus-group discussion cohorts (Abidjan, Nairobi and Dar es Salaam), comprising pre-selected countries that have already and those about to introduce the HPV vaccine. In each country, the EPI manager, the NITAG chair or representatives and an HPV-focal researcher were selected participants. The methods involved a collaborative and knowledge-sharing format through regional and country-specific discussions, plenary discussions, and workshop-style group missions. Results: The study reached a total of 78 key stakeholders, comprising 30 participants in cohort one, 21 in cohort two and 27 in cohort three. Key outcomes included the prevalence of declining HPV2 vaccination across all countries in the region; country-specific barriers impeding uptake were identified and strategy for accelerating vaccination demand initiated, e.g., utilizing investments from COVID-19 (e.g., electronic registry and multisector coordination); individual countries developing their respective HPV vaccination recovery and acceleration roadmaps; the identification and inclusion of a zero-dose catch-up strategy into the vaccination roadmaps; support for a transition from multiple-doses to a single-dose HPV vaccine; the incorporation of implementation science research to support the decision-making process such as vaccine choices, doses and understanding behavior. Conclusion: Beyond research, the study shows the significance of scientific approaches that are not limited to understanding problems, but are also solution-oriented, e.g., development of roadmaps to overcome barriers against HPV vaccination uptake. Full article

The aim of this study was to analyse the impact of the introduction of universal adolescent HBV vaccination on the incidence of acute hepatitis B virus (HBV) infections. Acute HBV cases reported to the Spanish National Epidemiological Surveillance Network between 2005 and 2021 were included. For regions starting adolescent vaccination in 1991–1993 and in 1994–1996, HBV incidence rates were compared by calculating the incidence rate ratio (IRR) and 95% confidence interval (CI). We also analysed the 2017 Spanish national seroprevalence survey data. The overall acute HBV incidence per 100,000 persons was 1.54 in 2005 and 0.64 in 2021 (p < 0.001). The incidence in 2014–2021 was lower for regions that started adolescent vaccination in 1991–1993 rather than in 1994–1996 (IRR 0.76; 95% CI 0.72–0.83; p < 0.001). In the 20–29 age group, incidence in regions that started adolescent vaccination in 1991–1993 was also lower (IRR 0.87; 95% CI 0.77–0.98; p = 0.02 in 2005–2013 and IRR 0.71; 95% CI 0.56–0·90; p < 0.001 in 2014–2021). Anti-HBc prevalence in the 35–39 age group was lower in the regions that started vaccination earlier, although the difference was not statistically significant (p = 0.09). Acute HBV incidence decreased more in the young adult population in regions that began adolescent vaccination earlier. Maintaining high universal vaccination coverage in the first year of life and in at-risk groups is necessary to achieve HBV elimination by 2030. Full article

Transmissibility and immune evasion of the recently emerged, highly mutated SARS-CoV-2 BA.2.87.1 are unknown. Here, we report that BA.2.87.1 efficiently enters human cells but is more sensitive to antibody-mediated neutralization than the currently dominating JN.1 variant. Acquisition of adaptive mutations might thus be needed for efficient spread in the population. Full article

Perceptions of the complete eradication of vaccine-preventable diseases such as measles, mumps, and rubella (MMR) may foster complacency and compromise vaccination efforts. Decreased measles vaccination rates during the COVID-19 pandemic have heightened the risk of outbreaks, even in adequately vaccinated populations. To address this, we have aligned with ECDC recommendations, leveraging previous cross-border sero-epidemiological assessments between Pécs, Hungary, and Osijek, Croatia, to identify latent risk groups and uncover potential parallels between our nations. Testing 2680 Hungarian and 1764 Croatian serum samples for anti-MMR IgG via ELISAs revealed anti-measles seropositivity ratios below expectations in Croatian cohorts aged ~20–30 (75.7%), ~30–40 (77.5%) and ~40–50 years (73.3%). Similarly, Hungarian samples also showed suboptimal seropositivity ratios in the ~30–40 (80.9%) and ~40–50 (87.3%) age groups. Considering mumps- and rubella-associated seropositivity trends, in both examined populations, individuals aged ~30–50 years exhibited the highest vulnerability. Additionally, we noted congruent seropositivity trends across both countries, despite distinct immunization and epidemiological contexts. Therefore, we propose expanding research to encompass the intricate dynamics of vaccination, including waning long-term immunity. This understanding could facilitate targeted interventions and bolster public awareness. Our findings underscore persistent challenges in attaining robust immunity against measles despite vaccination endeavors. Full article

West Nile virus (WNV) is capable of causing severe neurologic disease in both humans and equines, making it a disease of importance in both human medicine and veterinary medicine. No targeted treatments exist for WNV infection in either humans or equines. Infection is treated symptomatically through management of symptoms like fever and seizures. As treatment for WNV is purely supportive, the response to WNV has focused primarily on methods of disease prevention. To this end, research efforts have yielded several effective vaccines for equine use as well as numerous conventional mosquito control techniques. Even with the implementation of these techniques, disease caused by WNV remains a concern since no human vaccine exists. Due to the lack of a human vaccine, novel preventative strategies are under active research and development. Of these strategies, some of the most conceptually promising are techniques using genetically modified mosquitoes, addressing the disease at the vector level with minimal ecological side effects. Taken together, the use of combined, synergistic methods, such as physical barriers, transgenic mosquitoes, and immunological targets, will be the best way to prevent WNV disease. Full article

The WHO reported an estimated 249 million malaria cases and 608,000 malaria deaths in 85 countries in 2022. A total of 94% of malaria deaths occurred in Africa, 80% of which were children under 5. In other words, one child dies every minute from malaria. The RTS,S/AS01 malaria vaccine, which uses the Plasmodium falciparum circumsporozoite protein (CSP) to target sporozoite infection of the liver, achieved modest efficacy. The Malaria Vaccine Implementation Program (MVIP), coordinated by the WHO and completed at the end of 2023, found that immunization reduced mortality by only 13%. To further reduce malaria death, the development of a more effective malaria vaccine is a high priority. Three malaria vaccine targets being considered are the sporozoite liver infection (pre-erythrocytic stage), the merozoite red blood cell infection (asexual erythrocytic stage), and the gamete/zygote mosquito infection (sexual/transmission stage). These targets involve specific ligand-receptor interactions. However, most current malaria vaccine candidates that target two major parasite population bottlenecks, liver infection, and mosquito midgut infection, do not focus on such parasite ligands. Here, we evaluate the potential of newly identified parasite ligands with a phage peptide-display technique as novel malaria vaccine antigens. Full article

Tuberculosis (TB) remains a major infectious disease partly due to the lack of an effective vaccine. Therefore, developing new and more effective TB vaccines is crucial for controlling TB. Mycobacterium tuberculosis (M. tuberculosis) usually parasitizes in macrophages; therefore, cell-mediated immunity plays an important role. The maintenance of memory T cells following M. tuberculosis infection or vaccination is a hallmark of immune protection. This review analyzes the development of memory T cells during M. tuberculosis infection and vaccine immunization, especially on immune memory induced by BCG and subunit vaccines. Furthermore, the factors affecting the development of memory T cells are discussed in detail. The understanding of the development of memory T cells should contribute to designing more effective TB vaccines and optimizing vaccination strategies. Full article

COVID-19 vaccination strategies, including heterologous prime–boost regimens and additional booster doses, aim to optimize immune responses. However, seroepidemiological studies on immune responses to different COVID-19 vaccine types and schedules remain limited. This study investigated antibody levels following homologous and heterologous prime-and-boost COVID-19 vaccination in Bangladesh. In a cohort of 606 participants who received first/second/booster doses of vaccines (AstraZeneca, Moderna, Pfizer-BioNTech, and Sinopharm), anti-spike IgG and anti-nucleocapsid IgG levels were measured. Antibody titer variations with respect to age, gender, intervals between doses, and prior infection status were analyzed. mRNA vaccines elicited the highest antibody levels after homologous and heterologous boosting. The AstraZeneca booster resulted in a sharp titer decline rate of ~0.04 units per day. Second or booster vaccine doses significantly increased antibody levels, especially in males (p < 0.05). Older age correlated with higher titers, likely reflecting previous infection, which was further confirmed by the elevation of anti-nucleocapsid IgG levels. About 95.5% of non-Sinopharm recipients were anti-nucleocapsid IgG positive, suggesting prior exposure exceeding self-reported infections (12.5%). mRNA and heterologous COVID-19 boosting enhances humoral immunity over homologous prime–boost vector/inactivated vaccination. However, waning immunity merits further investigation across vaccine platforms. Full article

Influenza pandemics pose a serious risk to the global population, with the potential for high morbidity and mortality. An adjuvanted H5N1 vaccine (aH5N1) has been approved for prophylaxis against the avian influenza virus H5N1, which is a likely cause of future pandemics. In this phase-III, stratified, randomized, controlled, observer-blind, multicenter study, we evaluated the safety and immunogenicity of aH5N1 in four separate groups of adults: adults 18–60 years of age who were healthy or had high-risk medical conditions and older adults ≥61 years of age who were healthy or had high-risk medical conditions. Subjects were randomly assigned to aH5N1 or the comparator, adjuvanted trivalent seasonal influenza vaccine (aTIV). Antibody responses to aH5N1 were increased in all four subgroups and, within each age stratum, largely consistent between healthy subjects and those with medical conditions. Injection-site pain was reported by 66–73% of younger and 36–42% of older–aH5N1 recipients, and fatigue and myalgia were reported by 22–41% of subjects across age and health subgroups. No serious adverse events or deaths were considered related to the study vaccine. In conclusion, aH5N1 increased antibody responses regardless of age or health status and demonstrated a clinically acceptable safety and tolerability profile. Full article

This research study aimed to assess the reliability and validity of the Turkish version of the Vaccine Acceptance Instrument (VAI). The VAI is a 20-item Likert-type scale, with responses ranging across seven points. A systematic approach was followed to translate the scale into Turkish, involving translation, expert panel evaluation, back-translation, and pilot testing. The Vaccine Acceptance Instrument and a sociodemographic data form were used for data collection. The reliability of the scale was tested by test–retest analysis, and its internal reliability was examined by Cronbach’s alpha test. The factor structure was examined using Exploratory Factor Analysis (EFA). Confirmatory Factor Analysis (CFA) was employed to assess the scale’s fit. Overall, 229 participants were included in the study. In test–retest reliability analysis, the intraclass correlation coefficient of the scale was 0.992 (95% CI: 0.987–0.996). The Cronbach’s alpha value of the scale was 0.824. A four-factor structure was determined. The model had an acceptable fit [χ²/df = 380.04/164 (2,317) p < 0.001, CFI = 0.91, GFI = 0.90, AGFI = 0.906, NFI = 0.90, RMSEA = 0.076]. The mean total VAI score was 112.71 ± 17.02. The low education level of the mother, being a housewife, and parents not having the COVID-19 vaccine were statistically significantly associated with a low scale score and low vaccine acceptance (p < 0.05). The Turkish adaptation of the VAI demonstrated satisfactory levels of validity and reliability following rigorous testing. Full article

Age alters the host’s susceptibility to immune induction. Humoral immunity with circulating antibodies, particularly immunoglobulin G (IgG), plays an essential role in immune response. IgG glycosylation in the fragment crystallizable (Fc) region, including sialylation, is important in regulating the effector function by interacting with Fc gamma receptors (FcγRs). Glycosylation is fundamentally changed with age and inflammatory responses. We aimed to explore the regulation of humoral immunity by comparing responses to antigen-induced immune challenges in young and adult mice using a local antigen-induced arthritis mouse model. This study examines the differences in immune response between healthy and immune-challenged states across these groups. Our initial assessment of the arthritis model indicated that adult mice presented more severe knee swelling than their younger counterparts. In contrast, we found that neither histological assessment, bone mineral density, nor the number of osteoclasts differs. Our data revealed an age-associated but not immune challenge increase in total IgG; the only subtype affected by immune challenge was IgG1 and partially IgG3. Interestingly, the sialylation of IgG2b and IgG3 is affected by age and immune challenges but not stimulated further by immune challenges in adult mice. This suggests a shift in IgG towards a pro-inflammatory and potentially pathogenic state with age and inflammation. Full article

Despite significant strides in vaccine research and the availability of vaccines for many infectious diseases, the threat posed by both known and emerging infectious diseases persists. Moreover, breakthrough infections following vaccination remain a concern. Therefore, the development of novel vaccines is imperative. These vaccines must exhibit robust protective efficacy, broad-spectrum coverage, and long-lasting immunity. One promising avenue in vaccine development lies in leveraging T-cells, which play a crucial role in adaptive immunity and regulate immune responses during viral infections. T-cell recognition can target highly variable or conserved viral proteins, and memory T-cells offer the potential for durable immunity. Consequently, T-cell-based vaccines hold promise for advancing vaccine development efforts. This review delves into the latest research advancements in T-cell-based vaccines across various platforms and discusses the associated challenges. Full article

Tuberculosis, caused by Mycobacterium tuberculosis (M. tuberculosis), remains a formidable global health challenge, affecting a substantial portion of the world’s population. The current tuberculosis vaccine, bacille Calmette–Guérin (BCG), offers limited protection against pulmonary tuberculosis in adults, underscoring the critical need for innovative vaccination strategies. Cytokines are pivotal in modulating immune responses and have been explored as potential adjuvants to enhance vaccine efficacy. The strategic inclusion of cytokines as adjuvants in tuberculosis vaccines holds significant promise for augmenting vaccine-induced immune responses and strengthening protection against M. tuberculosis. This review delves into promising cytokines, such as Type I interferons (IFNs), Type II IFN, interleukins such as IL-2, IL-7, IL-15, IL-12, and IL-21, alongside the use of a granulocyte–macrophage colony-stimulating factor (GM-CSF) as an adjuvant, which has shown effectiveness in boosting immune responses and enhancing vaccine efficacy in tuberculosis models. Full article

Outbreaks caused by foot-and-mouth disease (FMD) A/ASIA/G-VII lineage viruses have often occurred in Middle Eastern and Southeast Asian countries since 2015. Because A/ASIA/G-VII lineage viruses are reported to have distinct antigenic relatedness with available commercial FMD vaccine strains, it is necessary to investigate whether inoculation with vaccines used in Korea could confer cross-protection against A/ASIA/G-VII lineage viruses. In the present study, we conducted two vaccination challenge trials to evaluate the efficacy of three commercial FMD vaccines (O/Manisa + O/3039 + A/Iraq, O/Campos + A/Cruzeiro + A/2001, and O/Primorsky + A/Zabaikalsky) against heterologous challenge with ASIA/G-VII lineage viruses (A/TUR/13/2017 or A/BHU/3/2017 strains) in pigs. In each trial, clinical signs, viremia, and salivary shedding of virus were measured for 7 days after challenge. In summary, the O/Campos + A/Cruzeiro + A/2001 vaccine provided full protection against two A/ASIA/G-VII lineage viruses in vaccinated pigs, where significant protection was observed. Although unprotected animals were observed in groups vaccinated with O/Manisa + O/3039 + A/Iraq or O/Primorsky + A/Zabaikalsky vaccines, the clinical scores and viral RNA levels in the sera and oral swabs of vaccinated animals were significantly lower than those of unvaccinated controls. Full article

During the COVID-19 pandemic, several vaccines were developed to limit the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, due to SARS-CoV-2 mutations and uneven vaccination coverage among populations, a series of COVID-19 waves have been caused by different variants of concern (VOCs). Despite the updated vaccine formulations for the new VOC, the benefits of additional COVID-19 vaccine doses have raised many doubts, even among high-risk groups such as healthcare workers (HCWs). We examined the factors underlying hesitancy to receive COVID-19 booster vaccine doses and analysed the anti-SARS-CoV-2 IgG antibody response after booster vaccination among HCWs. Our study found that 42% of the HCWs were hesitant about the second booster dose, while 7% reported no intent to get vaccinated with any additional doses. As reasons for not vaccinating, participants most frequently highlighted lack of time, negative experiences with previous vaccinations, and immunity conferred by past infections. In addition, we found the lowest post-vaccination antibody titres among HCWs who did not receive any vaccine booster dose and the highest among HCWs vaccinated with two booster doses. Full article

Real-world clinical experience of using anti-programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer (SCLC) patients has rarely been reported. In this study, we aimed to perform a retrospective multicenter clinical analysis of extensive-stage SCLC patients receiving first-line therapy with anti-PD-L1 ICIs combined with chemotherapy. Between November 2018 and March 2022, 72 extensive-stage SCLC patients receiving first-line atezolizumab or durvalumab in combination with chemotherapy, according to the cancer center databases of Linkou, Chiayi, and Kaohsiung Chang Gung Memorial Hospitals, were retrospectively included in the analysis. Twenty-one patients (29.2%) received atezolizumab and fifty-one (70.8%) received durvalumab. Objective response (OR) and disease control (DC) rates of 59.7% and 73.6%, respectively, were observed with first-line ICI plus chemotherapy. The median progression-free survival (PFS) was 6.63 months (95% confidence interval (CI), 5.25–8.02), and the median overall survival (OS) was 16.07 months (95% CI, 15.12–17.0) in all study patients. A high neutrophil-to-lymphocyte ratio (NLR; >4) and a high serum lactate dehydrogenase (LDH) concentration (>260 UL) were identified as independent unfavorable factors associated with shorter OS in the multivariate analysis. Regarding safety, neutropenia was the most common grade 3 treatment-related adverse event (AE), but no treatment-related deaths occurred in the study patients. First-line anti-PD-L1 ICIs combined with chemotherapy are effective and safe for male extensive-stage SCLC patients. Further therapeutic strategies may need to be developed for patients with unfavorable outcomes (e.g., baseline high NLR and serum LDH level). Full article

The COVID-19 pandemic has globally disrupted immunisation practices, impacting vulnerable populations such as pregnant women (PW), who harbour concerns about future children’s immunisations. This study aimed to assess the pandemic’s impact on PW’s attitudes towards childhood vaccinations. During three consecutive flu seasons from October 2019 to January 2022, a cross-sectional study was conducted in a large Italian teaching hospital using a questionnaire. The chi-square test was performed to compare each season. Across the 2019–2020 to 2021–2022 seasons, course attendance by PW surged from 105 to 340. Significant shifts in vaccination intentions were noted, including a 7.5% decrease in measles vaccination intent (p = 0.02) and a 10% decrease in that of pertussis (p = 0.004) from 2019–2020 to 2020–2021. While perceived contagion risk decreased, disease severity perceptions increased, with few significant differences. A statistically significant reduction was noted in the proportion of participants suspecting economic motives behind NHS workers’ promotion of childhood vaccinations. Furthermore, the pandemic period saw an increase in the perceived utility of non-institutional websites and the advice of physicians outside the NHS. These findings will help develop evidence-based, tailored interventions and communication strategies to address vaccine hesitancy and ensure optimal vaccination coverage among children born during and after the pandemic. Full article

Bacterial ghosts (BGs) are hollow bacterial cell envelopes with intact cellular structures, presenting as promising candidates for various biotechnological and biomedical applications. However, the yield and productivity of BGs have encountered limitations, hindering their large-scale preparation and multi-faceted applications of BGs. Further optimization of BGs is needed for the commercial application of BG technology. In this study, we screened out the most effective lysis protein ID52-E-W4A among 13 mutants based on phage ID52 lysis protein E and optimized the liquid culture medium for preparing Escherichia coli Nissle 1917 (EcN). The results revealed a significantly higher lysis rate of ID52-E-W4A compared to that of ID52-E in the 2xYT medium. Furthermore, EcN BGs were cultivated in a fermenter, achieving an initial OD₆₀₀ as high as 6.0 after optimization, indicating enhanced BG production. Moreover, the yield of ID52-E-W4A-induced BGs reached 67.0%, contrasting with only a 3.1% yield from φX174-E-induced BGs. The extended applicability of the lysis protein ID52-E-W4A was demonstrated through the preparation of Salmonella pullorum ghosts and Salmonella choleraesuis ghosts. Knocking out the molecular chaperone gene slyD and dnaJ revealed that ID52-mediated BGs could still undergo lysis. Conversely, overexpression of integral membrane enzyme gene mraY resulted in the loss of lysis activity for ID52-E, suggesting that the lysis protein ID52-E may no longer rely on SlyD or DnaJ to function, with MraY potentially being the target of ID52-E. This study introduces a novel approach utilizing ID52-E-W4A for recombinant expression, accelerating the BG formation and thereby enhancing BG yield and productivity. Full article

This study follows 99 subjects vaccinated with Pfizer/BioNTech COVID-19 vaccines over two years, with particular focus on the last year of observation (between days 360 and 720). The response to the vaccination was assessed with Diasorin’s SARS-CoV-2 TrimericSpike IgG. Screening for SARS-CoV-2 infection was performed with Abbott’s SARS-CoV-2 Nucleocapsid IgG immunoassay. Data from questionnaires were also analyzed. Two years after the first vaccine dose administration, 100% of the subjects were positive for anti-spike SARS-CoV-2 IgG and the median antibody level was still high (3600 BAU/mL), dropping insignificantly over the last year. Simultaneously, a substantial increase in seropositivity in anti-nucleocapsid SARS-CoV-2 IgG was noted, reaching 33%. There was no statistically significant agreement between anti-N seropositivity and reported COVID-19. Higher anti-spike concentrations and lower COVID-19 incidence was seen in the older vaccinees. It was noted that only subjects boosted between days 360 and 720 showed an increase in anti-spike IgG concentrations. The higher antibody concentrations (median 7440 BAU/mL) on day 360 were noted in participants not infected over the following year. Vaccination, including booster administrations, and natural, even unrecognized, contact with SARS-CoV-2 entwined two years after the primary vaccination, leading to high anti-spike antibody concentrations. Full article

Respiratory tract diseases caused by influenza virus and SARS-CoV-2 can represent a serious threat to the health of pregnant women. Immunological remodulation for fetus tolerance and physiological changes in the gestational chamber expose both mother and child to fearful complications and a high risk of hospitalization. Vaccines to protect pregnant women from influenza and COVID-19 are strongly recommended and vaccine co-administration could be advantageous to increase coverage of both vaccines. The attitude to accept both vaccines is affected by several factors: social, cultural, and cognitive-behavioral. In Palermo, Italy, during the 2021–2022 influenza season, a cross-sectional study was conducted to evaluate pregnant women’s intention to adhere to co-administration of influenza and COVID-19 vaccines. The determinants of vaccination attitude were investigated through the administration of a questionnaire and the Health Action Process Approach theory was adopted to explore the cognitive behavioral aspects. Overall, 120 pregnant women were enrolled; mean age 32 years, 98.2% (n = 118) of Italian nationality and 25.2% (n = 30) with obstetric or pathological conditions of pregnancy at risk. Factors significantly associated with the attitude to co-administration of influenza and COVID-19 vaccines among pregnant women were: high level of education (OR = 13.96; p < 0.001), positive outcome expectations (OR = 2.84; p < 0.001), and self-efficacy (OR = 3.1; p < 0.001). Effective strategies to promote the co-administration of the influenza vaccine and the COVID-19 vaccine should be based on the communication of the benefits and positive outcomes of vaccine co-administration and on the adequate information of pregnant women. Full article

Multivalent pneumococcal vaccines have been developed successfully to combat invasive pneumococcal diseases (IPD) and reduce the associated healthcare burden. These vaccines employ pneumococcal capsular polysaccharides (PnPs), either conjugated or unconjugated, as antigens to provide serotype-specific protection. Pneumococcal capsular polysaccharides used for vaccine often contain residual levels of cell wall polysaccharides (C-Ps), which can generate a non-serotype specific immune response and complicate the desired serotype-specific immunity. Therefore, the C-P level in a pneumococcal vaccine needs to be controlled in the vaccine process and the anti C-P responses need to be dialed out in clinical assays. Currently, two types of cell-wall polysaccharide structures have been identified: a mono-phosphocholine substituted cell-wall polysaccharide C-Ps1 and a di-phosphocholine substituted C-Ps2 structure. In our effort to develop a next-generation novel pneumococcal conjugate vaccine (PCV), we have generated a monoclonal antibody (mAb) specific to cell-wall polysaccharide C-Ps2 structure. An antibody-enhanced HPLC assay (AE-HPLC) has been established for serotype-specific quantification of pneumococcal polysaccharides in our lab. With the new anti C-Ps2 mAb, we herein extend the AE-HPLC assay to the quantification and identification of C-Ps2 species in pneumococcal polysaccharides used for vaccines. Full article

This systematic review and meta-analysis aimed to compare the immunogenicity and safety of an additional heterologous (viral vector) versus homologous (mRNA) COVID-19 vaccine dose among non-seroconverted immunocompromised patients after a two-dose primary series of mRNA vaccine. We searched studies published up to 21 June 2023 in PubMed, Scopus, and Embase. The meta-analysis was conducted to compare the seropositivity rates based on anti-SARS-CoV-2 spike protein IgG (anti-S IgG) and SARS-CoV-2-specific T-cell immune response rates, assessed by interferon-γ release assay at 4 weeks, and the incidences of serious adverse events (SAEs) within 28 days between the two vaccine regimens. In four included randomized controlled trials (RCTs), there were no statistically significant differences in the seropositive rate of anti-S IgG (risk ratio [RR]: 0.79, 95% CI: 0.48–1.29) and the concentration of SARS-CoV-2 interferon-γ (RR: 1.19, 95% CI: 0.96–1.48) between heterologous and homologous regimens. The heterologous regimen exhibited a significantly lower incidence of injection pain (RR: 0.55, 95% CI: 0.45–0.69), but a higher incidence of headache (RR: 1.44, 95% CI: 1.02–2.02) compared with the homologous regimen. No vaccine-related SAEs were reported within 28 days following vaccination. An additional heterologous or homologous COVID-19 vaccine dose was well tolerated and demonstrated a comparable vaccine immunogenicity among non-seroconverted immunocompromised patients who were initially vaccinated with a two-dose COVID-19 mRNA vaccine. This finding supports the recommendations of an extended primary series of COVID-19 vaccination in immunocompromised persons. Full article

Public antibody responses have been found against many infectious agents. Structural convergence of public antibodies is usually determined by immunoglobulin V genes. Recently, a human antibody public class against SARS-CoV-2 was reported, where the D gene (IGHD3-22) encodes a common YYDxxG motif in heavy-chain complementarity-determining region 3 (CDR H3), which determines specificity for the receptor-binding domain (RBD). In this review, we discuss the isolation, structural characterization, and genetic analyses of this class of antibodies, which have been isolated from various cohorts of COVID-19 convalescents and vaccinees. All eleven YYDxxG antibodies with available structures target the SARS-CoV-2 RBD in a similar binding mode, where the CDR H3 dominates the interaction with antigen. The antibodies target a conserved site on the RBD that does not overlap with the receptor-binding site, but their particular angle of approach results in direct steric hindrance to receptor binding, which enables both neutralization potency and breadth. We also review the properties of CDR H3-dominant antibodies that target other human viruses. Overall, unlike most public antibodies, which are identified by their V gene usage, this newly discovered public class of YYDxxG antibodies is dominated by a D-gene-encoded motif and uncovers further opportunities for germline-targeting vaccine design. Full article

In the current COVID-19 landscape dominated by Omicron subvariants, understanding the timing and efficacy of vaccination against emergent lineages is crucial for planning future vaccination campaigns, yet detailed studies stratified by subvariant, vaccination timing, and age groups are scarce. This retrospective study analyzed COVID-19 cases from December 2021 to January 2023 in Catalonia, Spain, focusing on vulnerable populations affected by variants BA.1, BA.2, BA.5, and BQ.1 and including two national booster campaigns. Our database includes detailed information such as dates of diagnosis, hospitalization and death, last vaccination, and cause of death, among others. We evaluated the impact of vaccination on disease severity by age, variant, and vaccination status, finding that recent vaccination significantly mitigated severity across all Omicron subvariants, although efficacy waned six months post-vaccination, except for BQ.1, which showed more stable levels. Unvaccinated individuals had higher hospitalization and mortality rates. Our results highlight the importance of periodic vaccination to reduce severe outcomes, which are influenced by variant and vaccination timing. Although the seasonality of COVID-19 is uncertain, our analysis suggests the potential benefit of annual vaccination in populations >60 years old, probably in early fall, if COVID-19 eventually exhibits a major peak similar to other respiratory viruses. Full article