Vaccines, Volume 11, Issue 11 (November 2023) – 106 articles

Mucosal vaccination appears to be suitable to protect against SARS-CoV-2 infection. In this study, we tested an intranasal mucosal vaccine candidate for COVID-19 that consisted of a cationic liposome containing a trimeric SARS-CoV-2 spike protein and CpG-ODNs, a Toll-like receptor 9 agonist, as an adjuvant. In vitro and in vivo experiments indicated the absence of toxicity following the intranasal administration of this vaccine formulation. First, we found that subcutaneous or intranasal vaccination protected hACE-2 transgenic mice from infection with the wild-type (Wuhan) SARS-CoV-2 strain, as shown by weight loss and mortality indicators. However, when compared with subcutaneous administration, the intranasal route was more effective in the pulmonary clearance of the virus and induced higher neutralizing antibodies and anti-S IgA titers. In addition, the intranasal vaccination afforded protection against gamma, delta, and omicron virus variants of concern. Furthermore, the intranasal vaccine formulation was superior to intramuscular vaccination with a recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 spike glycoprotein (Oxford/AstraZeneca) in terms of virus lung clearance and production of neutralizing antibodies in serum and bronchial alveolar lavage (BAL). Finally, the intranasal liposomal formulation boosted heterologous immunity induced by previous intramuscular vaccination with the Oxford/AstraZeneca vaccine, which was more robust than homologous immunity. Full article

Neuraminidase (NA)-based immunity could reduce the harmful impact of novel antigenic variants of influenza viruses. The detection of neuraminidase-inhibiting (NI) antibodies in parallel with anti-hemagglutinin (HA) antibodies may enhance research on the immunogenicity and duration of antibody responses to influenza vaccines. To assess anti-NA antibodies after vaccination with seasonal inactivated influenza vaccines, we used the enzyme-linked lectin assay, and anti-HA antibodies were detected in the hemagglutination inhibition assay. The dynamics of the anti-NA antibody response differed depending on the virus subtype: antibodies to A/H3N2 virus neuraminidase increased later than antibodies to A/H1N1pdm09 subtype neuraminidase and persisted longer. In contrast to HA antibodies, the fold increase in antibody titers to NA after vaccination poorly depended on the preexisting level. At the same time, NA antibody levels after vaccination directly correlated with titers before vaccination. A difference was found in response to NA antigen between split and subunit-adjuvanted vaccines and in NA functional activity in the vaccine formulations. Full article

The effectiveness of SARS-CoV-2 vaccines varies among individuals. During the COVID-19 global pandemic, SARS-CoV-2 infection showed significant Th1 characteristics, suggesting that the immune disorder and production of SARS-CoV-2 antibodies may be related to Th1/Th2 bias. However, the molecular mechanisms underlying Th1/Th2 bias effects on host immune responses to viruses remain unclear. In this study, the top three subjects with the highest and lowest changes in anti-SARS-CoV-2 antibodies after receiving three doses of SARS-CoV-2 vaccination were selected and defined as the elevated group (E) and the control group (C), respectively. Peripheral blood was collected, single-cell sequencing was performed before and after the third dose of the SARS-CoV-2 vaccine, and the changes in T cell clusters were analyzed. Compared with the C group, the Treg pre-vaccination proportion was lower in E, while the post-vaccination proportion was higher, suggesting that Tregs may be crucial in this process. Differential analysis results of Tregs between the two groups revealed that differentially expressed genes (DEGs) were significantly enriched in the IL4 pathway. Correlation analysis between DEGs and serum antibody showed that the expression of NR4A2, SOCS1, and SOCS3 in Tregs was significantly correlated with serum antibodies, suggesting that the immune response in E group changed to Th2 bias, thereby promoting host humoral immune responses. On the other hand, antibody-related genes SOCS1 and NR4A2, as well as lnc-RNA MALAT1 and NEAT1, were highly expressed in the CD4-MALAT1 subclusters. In summary, our study revealed that Th2 bias promotes humoral immune responses in humans by increasing SOCS1 in T cells after SARS-CoV-2 vaccination. Moreover, NR4A2, SOCS1, MALAT1, and NEAT1 were identified as the potential key biomarkers or treatment targets for enhanced SARS-CoV-2 antibody production by influencing the Th1/Th2 balance in T cells. Our findings have important implications for population stratification and tailored therapeutics for more effective SARS-CoV-2 vaccines. Full article

Recently, genetically stable novel OPVs (nOPV) were developed by modifying the genomes of Sabin viruses of conventional OPVs to reduce the risk of reversion to neurovirulence and therefore the risk of generating circulating vaccine-derived polioviruses. There is a need for specific and sensitive methods for the identification and quantification of nOPV viruses individually and in mixtures for clinical trials and potentially for manufacturing quality control and environmental surveillance. In this communication, we evaluated and improved the quantitative multiplex one-step reverse transcriptase polymerase chain reaction (qmosRT-PCR) assay for the identification and quantification of nOPV viruses in samples with different formulations and virus concentrations and in virus-spiked stool samples. The assay was able to specifically identify at least 1 log₁₀ CCID₅₀/mL of each serotype in the presence of the two other serotypes at high concentrations (6–7 log₁₀ CCID₅₀/mL) in the same sample. In addition, the lowest viral concentration that the assay was able to detect in stool samples was 17 CCID₅₀/mL for nOPV1 and nOPV2 viruses and 6 CCID₅₀/mL for nOPV3. We also found high correlation between the expected and observed (by qmosRT-PCR) concentrations of spiked viruses in stool samples for all three nOPV viruses, with R-squared values above 0.95. The analysis of samples collected from an nOPV2 clinical trial showed that 100% of poliovirus type 2 was detected and few samples showed the presence of type 1 and 3 residuals from previous vaccinations with bOPV (at least 4 weeks prior vaccination with nOPV2), confirming the high sensitivity of the method. The qmosRT-PCR was specific and sensitive for the simultaneous identification and quantification of all three nOPV viruses. It can be used as an identity test during the nOPV manufacturing process and in evaluation of virus excretion in nOPV clinical trials. Full article

Influenza is a contagious respiratory disease caused by the influenza virus. Vaccination proves an effective approach to preventing influenza and minimizing the risk of experiencing associated complications. However, the influenza vaccine coverage rate among Israeli college students is low due to a sense of complacency, lack of knowledge, and vaccine hesitancy. The current study examined the relationship between the level of trust in the healthcare system and influenza vaccine hesitancy among college students in Israel. This cross-sectional study was conducted via an online questionnaire in April–May 2023. In total, 610 students were surveyed, of whom 57% had been vaccinated against influenza in the past; however, only 12% were vaccinated this year. Negative, significant, and moderate relationships were found between the level of trust in the healthcare system and influenza vaccine hesitancy. Students who had been vaccinated in the past had a higher level of trust in the healthcare system and a lower level of vaccination hesitancy. The linear regression model revealed that the variables of being a woman, not Jewish, vaccinated, and trusting the Ministry of Health, family doctor, and health professionals were associated with a decrease in vaccine hesitancy. These findings are in line with previous research in the field. Based on the present results, it may be advisable to develop intervention programs aimed at increasing confidence in the healthcare system and vaccinations by providing knowledge and addressing students’ concerns regarding vaccination. Full article

Polymyxin B (PMB) is an antibiotic that exhibits mucosal adjuvanticity for ovalbumin (OVA), which enhances the immune response in the mucosal compartments of mice. Frequent breakthrough infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants indicate that the IgA antibody levels elicited by the mRNA vaccines in the mucosal tissues were insufficient for the prophylaxis of this infection. It remains unknown whether PMB exhibits mucosal adjuvanticity for antigens other than OVA. This study investigated the adjuvanticity of PMB for the virus proteins, hemagglutinin (HA) of influenza A virus, and the S1 subunit and S protein of SARS-CoV-2. BALB/c mice immunized either intranasally or subcutaneously with these antigens alone or in combination with PMB were examined, and the antigen-specific antibodies were quantified. PMB substantially increased the production of antigen-specific IgA antibodies in mucosal secretions and IgG antibodies in plasma, indicating its adjuvanticity for both HA and S proteins. This study also revealed that the PMB-virus antigen complex diameter is crucial for the induction of mucosal immunity. No detrimental effects were observed on the nasal mucosa or olfactory bulb. These findings highlight the potential of PMB as a safe candidate for intranasal vaccination to induce mucosal IgA antibodies for prophylaxis against mucosally transmitted infections. Full article

The coronavirus disease 2019 (COVID-19) pandemic exposed the vulnerability of pregnant women to excess morbidity and mortality, as well as the disproportionate disease burden in certain racial, ethnic, and sociodemographic groups. Vaccine hesitancy represents a major threat to public health, and crafting messages that reach vulnerable groups and address their intersectionality remains a weakness for pandemic preparedness. We sought to investigate factors that influenced vaccine acceptance and social media ad response in a mixed-methods study of Spanish-speaking women living in the rural Western United States who were pregnant or recently pregnant between November 2022 and June 2023. Direct interviews were translated, transcribed, and coded, while the ad ratings were analyzed using linear mixed models. Participants most favorably rated ads that featured doctors and text-heavy content describing benefits of vaccination. Qualitative data illustrated how information from trusted medical providers along with generational and cultural history of vaccine acceptance positively impacted perspectives on vaccination. Immigration status had varying influences on vaccination perspectives. Future vaccination campaigns targeting Spanish-speaking pregnant individuals in rural communities should use medical providers as ad messengers and dispel fears that vaccine acceptance may lead to problems with immigration status. Full article

Microarray patches (MAPs) have the potential to be a safer, more acceptable, easier-to-use, and more cost-effective means for the administration of vaccines than injection by needle and syringe. Here, we report findings from a randomized, partially double-blinded, placebo-controlled Phase I trial using the Vaxxas high-density MAP (HD-MAP) to deliver a measles rubella (MR) vaccine. Healthy adults (N = 63, age 18–50 years) were randomly assigned 1:1:1:1 to four groups: uncoated (placebo) HD-MAPs, low-dose MR HD-MAPs (~3100 median cell-culture infectious dose [CCID₅₀] measles, ~4300 CCID₅₀ rubella); high-dose MR-HD-MAPs (~9300 CCID₅₀ measles, ~12,900 CCID₅₀ rubella); or a sub-cutaneous (SC) injection of an approved MR vaccine, MR-Vac (≥1000 CCID₅₀ per virus). The MR vaccines were stable and remained viable on HD-MAPs when stored at 2–8 °C for at least 24 months. When MR HD-MAPs stored at 2–8 °C for 24 months were transferred to 40 °C for 3 days in a controlled temperature excursion, loss of potency was minimal, and MR HD-MAPs still met World Health Organisation (WHO) specifications. MR HD-MAP vaccination was safe and well-tolerated; any systemic or local adverse events (AEs) were mild or moderate. Similar levels of binding and neutralizing antibodies to measles and rubella were induced by low-dose and high-dose MR HD-MAPs and MR-Vac. The neutralizing antibody seroconversion rates on day 28 after vaccination for the low-dose HD-MAP, high-dose HD-MAP and MR-Vac groups were 37.5%, 18.8% and 35.7%, respectively, for measles, and 37.5%, 25.0% and 35.7%, respectively, for rubella. Most participants were seropositive for measles and rubella antibodies at baseline, which appeared to negatively impact the number of participants that seroconverted to vaccines delivered by either route. The data reported here suggest HD-MAPs could be a valuable means for delivering MR-vaccine to hard-to-reach populations and support further development. Clinical trial registry number: ACTRN12621000820808. Full article

Group A Streptococcus (GAS) is a major human pathogen for which there is no licensed vaccine. To protect against infection, a strong systemic and mucosal immune response is likely to be necessary to prevent initial colonization and any events that might lead to invasive disease. A broad immune response will be necessary to target the varied GAS serotypes and disease presentations. To this end, we designed a representative panel of recombinant proteins to cover the stages of GAS infection and investigated whether mucosal and systemic immunity could be stimulated by these protein antigens. We immunized mice sublingually, intranasally and subcutaneously, then measured IgG and IgA antibody levels and functional activity through in vitro assays. Our results show that both sublingual and intranasal immunization in the presence of adjuvant induced both systemic IgG and mucosal IgA. Meanwhile, subcutaneous immunization generated only a serum IgG response. The antibodies mediated binding and killing of GAS cells and blocked binding of GAS to HaCaT cells, particularly following intranasal and subcutaneous immunizations. Further, antigen-specific assays revealed that immune sera inhibited cleavage of IL-8 by SpyCEP and IgG by Mac/IdeS. These results demonstrate that mucosal immunization can induce effective systemic and mucosal antibody responses. This finding warrants further investigation and optimization of humoral and cellular responses as a viable alternative to subcutaneous immunization for urgently needed GAS vaccines. Full article

Significant progress has been made in vaccine development worldwide. This study examined the WHO African Region’s vaccine introduction trends from 2000 to 2022, excluding COVID-19 vaccines. We extracted data on vaccine introductions from the WHO/UNICEF joint reporting form for 17 vaccines. We examined the frequency and percentages of vaccine introductions from 2000 to 2022, as well as between two specific time periods (2000–2010 and 2011–2022). We analysed Gavi eligible and ineligible countries separately and used a Chi-squared test to determine if vaccine introductions differed significantly. Three vaccines have been introduced in all 47 countries within the region: hepatitis B (HepB), Haemophilus influenzae type b (Hib), and inactivated polio vaccine (IPV). Between 2011 and 2022, HepB, Hib, IPV, the second dose of measles-containing vaccine (MCV2), and pneumococcal conjugate vaccine (PCV) were the five most frequently introduced vaccines. Hepatitis A vaccine has only been introduced in Mauritius, while Japanese encephalitis vaccine has not been introduced in any African country. Between 2000–2010 and 2011–2022, a statistically significant rise in the number of vaccine introductions was noted (p < 0.001) with a significant positive association between Gavi eligibility and vaccine introductions (p < 0.001). Significant progress has been made in the introduction of new vaccines between 2000 and 2022 in the WHO African Region, with notable introductions between 2011 and 2022. Commitments from countries, and establishing the infrastructure required for effective implementation, remain crucial. Full article

Significant progress has been achieved in the realm of therapeutic interventions for multiple myeloma (MM), leading to transformative shifts in its clinical management. While conventional modalities such as surgery, radiotherapy, and chemotherapy have improved the clinical outcomes, the overarching challenge of effecting a comprehensive cure for patients afflicted with relapsed and refractory MM (RRMM) endures. Notably, adoptive cellular therapy, especially chimeric antigen receptor T-cell (CAR-T) therapy, has exhibited efficacy in patients with refractory or resistant B-cell malignancies and is now also being tested in patients with MM. Within this context, the B-cell maturation antigen (BCMA) has emerged as a promising candidate for CAR-T-cell antigen targeting in MM. Alternative targets include SLAMF7, CD38, CD19, the signaling lymphocyte activation molecule CS1, NKG2D, and CD138. Numerous clinical studies have demonstrated the clinical efficacy of these CAR-T-cell therapies, although longitudinal follow-up reveals some degree of antigenic escape. The widespread implementation of CAR-T-cell therapy is encumbered by several barriers, including antigenic evasion, uneven intratumoral infiltration in solid cancers, cytokine release syndrome, neurotoxicity, logistical implementation, and financial burden. This article provides an overview of CAR-T-cell therapy in MM and the utilization of BCMA as the target antigen, as well as an overview of other potential target moieties. Full article

SARS-CoV-2 mRNA vaccines are administered as effective prophylactic measures for reducing virus transmission rates and disease severity. To enhance the durability of post-vaccination immunity and combat SARS-CoV-2 variants, boosters have been administered to two-dose vaccinees. However, long-term humoral responses following booster vaccination are not well characterized. A 16-member cohort of healthy SARS-CoV-2 naïve participants were enrolled in this study during a three-dose BNT162b2 vaccine series. Serum samples were collected from vaccinees over 420 days and screened for antigen (Ag)-specific antibody titers, IgG subclass distribution, and neutralizing antibody (nAb) responses. Vaccine boosting restored peak Ag-specific titers with sustained α-RBD IgG and IgA antibody responses when measured at six months post-boost. RBD- and spike-specific IgG4 antibody levels were markedly elevated in three-dose but not two-dose immune sera. Although strong neutralization responses were detected in two- and three-dose vaccine sera, these rapidly decayed to pre-immune levels by four and six months, respectively. While boosters enhanced serum IgG Ab reactivity and nAb responses against variant strains, all variants tested showed resistance to two- and three-dose immune sera. Our data reflect the poor durability of vaccine-induced nAb responses which are a strong predictor of protection from symptomatic SARS-CoV-2 infection. The induction of IgG4-switched humoral responses may permit extended viral persistence via the downregulation of Fc-mediated effector functions. Full article

Advances in vaccinology have resulted in various new vaccines being introduced into recommended immunization schedules. Armenia introduced the rotavirus vaccine (RV) and the pneumococcal conjugate vaccine (PCV) into its national schedule in 2012 and 2014, respectively. Using data from the Armenia Demographic and Health Survey, the uptake of the RV and the PCV among children aged younger than three years was estimated. Multilevel logistic regression models were used to evaluate individual- and community-level factors associated with uptake. Intra-cluster correlations were estimated to explain variations in uptake between clusters. The uptake proportionof each RV dose were 90.0% and 86.6%, while each PCV dose had values of 83.5%, 79.4%, and 75.5%, respectively. Non-uptake was highest among children less than 6 months old, children with one sibling, children from a wealthy family, or children whose living distance to a health clinic was problematic. Significant variability in non-uptake due to cluster differences was found for both RV doses (30.5% and 22.8%, respectively) and for the second PCV dose (53.9%). When developing strategies for new vaccine implementation, characteristics of the child, such as age, siblingship, and distance to a health clinic or residence, should be considered. Further exploration of cluster differences may provide insights based on the increased uptake of these and other new vaccines. Full article

This study found a higher percentage of CD8⁺ T cells in piglets immunized with a CVC1302-adjuvanted inactivated foot-and-mouth disease virus (FMDV) vaccine. We wondered whether the CVC1302-adjuvanted inactivated FMDV vaccine promoted cellular immunity by promoting the antigen cross-presentation efficiency of ovalbumin (OVA) through dendritic cells (DCs), mainly via cytosolic pathways. This was demonstrated by the enhanced levels of lysosomal escape of OVA in the DCs loaded with OVA and CVC1302. The higher levels of ROS and significantly enhanced elevated lysosomal pH levels in the DCs facilitated the lysosomal escape of OVA. Significantly enhanced CTL activity levels was observed in the mice immunized with OVA-CVC1302. Overall, CVC1302 increased the cross-presentation of exogenous antigens and the cross-priming of CD8⁺ T cells by alkalizing the lysosomal pH and facilitating the lysosomal escape of antigens. These studies shed new light on the development of immunopotentiators to improve cellular immunity induced by vaccines. Full article

Immunotherapy using systemic immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T cells has revolutionized cancer treatment, but it only benefits a subset of patients. Systemic immunotherapies cause severe autoimmune toxicities and cytokine storms. Immune-related adverse events (irAEs) plus the immunosuppressive tumor microenvironment (TME) have been linked to the inefficacy of systemic immunotherapy. Intratumoral immunotherapy that increases immunotherapeutic agent bioavailability inside tumors could enhance the efficacy of immunotherapies and reduce systemic toxicities. In preclinical and clinical studies, intratumoral administration of immunostimulatory agents from small molecules to xenogeneic cells has demonstrated antitumor effects not only on the injected tumors but also against noninjected lesions. Herein, we review and discuss the results of these approaches in preclinical models and clinical trials to build the landscape of intratumoral immunotherapeutic agents and we describe how they stimulate the body’s immune system to trigger antitumor immunity as well as the challenges in clinical practice. Systemic and intratumoral combination immunotherapy would make the best use of the body’s immune system to treat cancers. Combining precision medicine and immunotherapy in cancer treatment would treat both the mutated targets in tumors and the weakened body’s immune system simultaneously, exerting maximum effects of the medical intervention. Full article

In mammals, the role of interleukin-18 (IL-18) in the immune response is to drive inflammatory and, normally therefore, anti-viral responses. IL-18 also shows promise as a vaccine adjuvant in mammals. Chicken IL-18 (chIL-18) has been cloned. The aim of this study was to investigate the potential of chIL-18 to act as a vaccine adjuvant in the context of a live recombinant Fowlpox virus vaccine (fpIBD1) against Infectious bursal disease virus (IBDV). fpIBD1 protects against mortality, but not against damage to the bursa of Fabricius caused by IBDV infection. The Fowlpox virus genome itself contains several candidate immunomodulatory genes, including potential IL-18 binding proteins (IL-18bp). We knocked out (Δ) the potential IL-18bp genes in fpIBD1 and inserted (::) the cDNA encoding chIL-18 into fpIBD1 in the non-essential ORF030, generating five new viral constructs –fpIBD1::chIL-18, fpIBD1ΔORF073, fpIBD1ΔORF073::chIL-18, fpIBD1ΔORF214, and fpIBD1ΔORF214::chIL-18. The subsequent protection from challenge with virulent IBDV, as measured by viral load and bursal damage, given by these altered fpIBD1 strains, was compared to that given by the original fpIBD1. Complete protection was provided following challenge with IBDV in chicken groups vaccinated with either fpIBDIΔ073::IL-18 or fpIBD1Δ214::IL-18, as no bursal damage nor IBDV was detected in the bursae of the birds. The results show that chIL-18 can act as an effective vaccine adjuvant by improving the fpIBD1 vaccine and providing complete protection against IBDV challenge. Full article

Worldwide, conjugated pneumococcal vaccines (PCVs) have proven effective against invasive pneumococcal disease, but non-invasive pneumonia is a major cause of mortality in young children and serotypes vary geographically, affecting effectiveness. We analyze nationwide death certificate data between 2003–2017 to assess the impact of PCVs on pneumonia mortality among young children from Peru. We report descriptive statistics and perform timeseries analysis on annual mortality rates (AMRs) and monthly frequencies of pneumonia deaths. Children under 5 years of age accounted for 6.2% (n = 10,408) of all pneumonia deaths (N = 166,844), and 32.3% (n = 3363) were children between 1–4 years of age, of which 95.1% did not report pneumonia etiology. Comparing periods before and after PCV introduction in 2009, mean AMRs dropped 13.5% and 26.0% for children between 1–4 years of age (toddlers/preschoolers), and children under 1 year of age (infants), respectively. A moderate correlation (Spearman’s r = 0.546, p < 0.01) in the monthly frequency of pneumonia deaths was estimated between both age groups. Quadratic regression suggests a change in direction around 2005 (highest pneumonia mortality) for both age groups, but percentage change analysis identified an inflection point in 2013 for infants only, not for toddlers/preschoolers, suggesting that the impact of PCVs might be different for each age group. Full article

The declaration of the conclusion of the COVID-19 pandemic notwithstanding, coronavirus remains prevalent in circulation, and the potential emergence of novel variants of concern introduces the possibility of new outbreaks. Moreover, it is not clear how quickly and to what extent the effectiveness of vaccination will decline as the virus continues to mutate. One possible solution to combat the rapidly mutating coronavirus is the creation of safe vaccine platforms that can be rapidly adapted to deliver new, specific antigens in response to viral mutations. Recombinant probiotic microorganisms that can produce viral antigens by inserting specific viral DNA fragments into their genome show promise as a platform and vector for mucosal vaccine antigen delivery. The authors of this study have developed a convenient and universal technique for inserting the DNA sequences of pathogenic bacteria and viruses into the gene that encodes the pili protein of the probiotic strain E. faecium L3. The paper presents data on the immunogenic properties of two E. faecium L3 vaccine strains, which produce two different fragments of the coronavirus S1 protein, and provides an assessment of the protective efficacy of these oral vaccines against coronavirus infection in Syrian hamsters. Full article

Background: Pregnant women are at an increased risk of hospitalisation, admission to the intensive care unit, mechanical ventilation, and death from SARS-CoV-2 infection. The aim of this study is to determine the predictive factors associated with COVID-19 vaccine uptake during pregnancy over time in a population with a high background uptake of maternal influenza and pertussis vaccination. Methods: This is a population-based, cohort study of all pregnant women who gave birth in Victoria, Australia between 1 July 2021 and 30 June 2022. Data from the Victorian Perinatal Data Collection were analysed using univariable and multivariable logistic regression. Results: This study reports on 77,719 women who gave birth over a 12 month period, of whom 49,281 (63.4%) received a COVID-19 vaccine, 54,887 (70.6%) received an influenza vaccination and 63,594 (81.8%) received a pertussis vaccine by the time of delivery. Pregnant women aged >30 years (aOR 1.31 CI 1.27, 1.36), who had >=8 antenatal visits (aOR 1.08 CI 1.04, 1.12), and those who received influenza vaccine (aOR 1.23 CI 1.19, 1.28) were more likely to have received a COVID-19 vaccine. Those who smoked (aOR 0.7 CI 0.66, 0.74), were First Nations (aOR 0.83 CI 0.74, 0.93) and those who gave birth in public hospitals (aOR 0.65 CI 0.63, 0.68) were less likely to receive COVID-19 vaccine in the first 12 months of the rollout. Conclusion: Maternal age, smoking, parity and Indigenous status were factors associated with delayed and sustained lower coverage, even in a population with background maternal influenza and pertussis coverage of 70.6% and 81.8%, respectively. Full article

Seasonal influenza is a leading cause of death in the U.S., causing significant morbidity, mortality, and economic burden. Despite the proven efficacy of vaccinations, rates remain notably low, especially among Medicaid enrollees. Leveraging Medicaid claims data, this study characterizes influenza vaccination rates among Medicaid enrollees and aims to elucidate factors influencing vaccine uptake, providing insights that might also be applicable to other vaccine-preventable diseases, including COVID-19. This study used Medicaid claims data from nine U.S. states (2016–2021], encompassing three types of claims: fee-for-service, major Medicaid managed care plan, and combined. We included Medicaid enrollees who had an in-person healthcare encounter during an influenza season in this period, excluding those under 6 months of age, over 65 years, or having telehealth-only encounters. Vaccination was the primary outcome, with secondary outcomes involving in-person healthcare encounters. Chi-square tests, multivariable logistic regression, and Fisher’s exact test were utilized for statistical analysis. A total of 20,868,910 enrollees with at least one healthcare encounter in at least one influenza season were included in the study population between 2016 and 2021. Overall, 15% (N = 3,050,471) of enrollees received an influenza vaccine between 2016 and 2021. During peri-COVID periods, there was an increase in vaccination rates among enrollees compared to pre-COVID periods, from 14% to 16%. Children had the highest influenza vaccination rates among all age groups at 29%, whereas only 17% were of 5–17 years, and 10% were of the 18–64 years were vaccinated. We observed differences in the likelihood of receiving the influenza vaccine among enrollees based on their health conditions and medical encounters. In a study of Medicaid enrollees across nine states, 15% received an influenza vaccine from July 2016 to June 2021. Vaccination rates rose annually, peaking during peri-COVID seasons. The highest uptake was among children (6 months–4 years), and the lowest was in adults (18–64 years). Female gender, urban residency, and Medicaid-managed care affiliation positively influenced uptake. However, mental health and substance abuse disorders decreased the likelihood. This study, reliant on Medicaid claims data, underscores the need for outreach services. Full article

The emergence of Omicron variants coincided with declining vaccine-induced protection against SARS-CoV-2. Two bivalent mRNA vaccines, mRNA-1273.222 (Moderna) and BNT162b2 Bivalent (Pfizer-BioNTech), were developed to provide greater protection against the predominate circulating variants by including mRNA that encodes both the ancestral (original) strain and BA.4/BA.5. We estimated their relative vaccine effectiveness (rVE) in preventing COVID-19-related outcomes in the US using a nationwide dataset linking primary care electronic health records and pharmacy/medical claims data. The study population (aged ≥18 years) received either vaccine between 31 August 2022 and 28 February 2023. We used propensity score weighting to adjust for baseline differences between groups. We estimated the rVE against COVID-19-related hospitalizations (primary outcome) and outpatient visits (secondary) for 1,034,538 mRNA-1273.222 and 1,670,666 BNT162b2 Bivalent vaccine recipients, with an adjusted rVE of 9.8% (95% confidence interval: 2.6–16.4%) and 5.1% (95% CI: 3.2–6.9%), respectively, for mRNA-1273.222 versus BNT162b2 Bivalent. The incremental relative effectiveness was greater among adults ≥ 65; the rVE against COVID-19-related hospitalizations and outpatient visits in these patients was 13.5% (95% CI: 5.5–20.8%) and 10.7% (8.2–13.1%), respectively. Overall, we found greater effectiveness of mRNA-1273.222 compared with the BNT162b2 Bivalent vaccine in preventing COVID-19-related hospitalizations and outpatient visits, with increased benefits in older adults. Full article

There is limited available data addressing whether inactivated COVID-19 vaccination before conception is associated with adverse neonatal outcomes. This cohort study included all singleton live births at our center from March 1 to June 30, 2022. According to whether a maternal inactivated COVID-19 vaccination had been administered within 3 months before conception or not, neonates were identified as being in the vaccinated or unvaccinated group. Vaccination information and clinical characteristics were extracted for analysis. Furthermore, neonatal outcomes were analyzed and compared between these two groups in the present study. The cohort included 856 eligible newborns, of whom 369 were exposed to maternal vaccination before conception and 487 were unexposed newborns. No differences were observed in rates of preterm birth, newborns being small for gestational age, or neonatal intensive care unit admission between exposed and unexposed newborns. Furthermore, even after adjusting for social–economic status and maternal characteristics, there remained no significant differences in these neonatal outcomes. Our study revealed no statistically significant differences between newborns born to women who received inactivated vaccines prior to conception compared with those who did not receive any vaccinations. In addition, our study also highlights the importance of considering COVID-19 vaccination before conception. Full article

Although the Government of Nepal has achieved high and sustained childhood vaccination coverage, reaching under-immunized and zero-dose children requires different approaches. Behavioral science offers promise in better understanding the drivers of vaccination and development of more effective programs; however, the application of behavioral science to immunization programs in Nepal is nascent. Through the Behavioral Science Immunization Network, JSI, UNICEF Nepal, and Dhulikhel Hospital–Kathmandu University School of Medical Sciences established a Behavioral Science Center to engage a diverse group of stakeholders in increasing the capacity of practitioners to use behavioral science in immunization programming. As a result of the engagement during formative research, government stakeholders requested and applied tools from behavioral science to solve different immunization challenges. Of particular value was the use of the Journey to Health and Immunization framework, which helped stakeholders identify behavioral and social drivers of zero-dose communities in Kathmandu. Our experience in Nepal demonstrates that there is strong demand for approaches and tools from behavioral science to use in relation to immunization and that this type of engagement model is effective for generating demand for and strengthening capacity to use behavioral science approaches. Full article

Background: The variation in the reported vaccine safety and effectiveness could contribute to the high rates of vaccine hesitancy among the general population and healthcare workers in areas where monkeypox (mpox) is circulating. In this review, our objective was to evaluate the safety, immunogenicity, effectiveness, and efficacy of the mpox vaccines. Methods: An extensive search for articles across multiple databases was performed, including searching six databases (PubMed Central, PubMed Medline, Scopus, Web of Science, Cochrane, ProQuest), two pre-print databases (European PMC Preprint and MedRxiv), and Google Scholar. Results: A total of 4290 citations were retrieved from the included databases. Following the removal of duplicates and the initial screening of records, a total of 36 studies were included into the analysis. Additionally, we identified five more studies through manual searches, resulting in a total of 41 eligible articles for qualitative synthesis. The study findings revealed that mpox vaccines demonstrate the ability to generate adequate antibodies; however, their effectiveness may decrease over time, exhibiting varying safety profiles. Most of the included studies consistently reported substantial levels of effectiveness and efficacy against mpox. Interestingly, the number of vaccine doses administered was found to influence the degree of immunogenicity, subsequently impacting the overall effectiveness and efficacy of the vaccines. Furthermore, we found that smallpox vaccines exhibited a form of cross-protection against mpox. Conclusions: Vaccines can be used to prevent mpox and effectively control its spread. Full article

Swine influenza A viruses (SwIAVs) are pathogens of both veterinary and medical significance. Intranasal (IN) vaccination has the potential to reduce flu infection. We investigated the efficacy of split SwIAV H1N2 antigens adsorbed with a plant origin nanoparticle adjuvant [Nano11–SwIAV] or in combination with a STING agonist ADU-S100 [NanoS100–SwIAV]. Conventional pigs were vaccinated via IN and challenged with a heterologous SwIAV H1N1-OH7 or 2009 H1N1 pandemic virus. Immunologically, in NanoS100–SwIAV vaccinates, we observed enhanced frequencies of activated monocytes in the blood of the pandemic virus challenged animals and in tracheobronchial lymph nodes (TBLN) of H1N1-OH7 challenged animals. In both groups of the virus challenged pigs, increased frequencies of IL-17A⁺ and CD49d⁺IL-17A⁺ cytotoxic lymphocytes were observed in Nano11–SwIAV vaccinates in the draining TBLN. Enhanced frequency of CD49d⁺IFNγ⁺ CTLs in the TBLN and blood of both the Nano11-based SwIAV vaccinates was observed. Animals vaccinated with both Nano11-based vaccines had upregulated cross-reactive secretory IgA in the lungs and serum IgG against heterologous and heterosubtypic viruses. However, in NanoS100–SwIAV vaccinates, a slight early reduction in the H1N1 pandemic virus and a late reduction in the SwIAV H1N1-OH7 load in the nasal passages were detected. Hence, despite vast genetic differences between the vaccine and both the challenge viruses, IN vaccination with NanoS100–SwIAV induced antigen-specific moderate levels of cross-protective immune responses. Full article

Alzheimer disease (AD) is one of the most common and disabling neuropathies in the ever-growing aged population around the world, that especially affects Western countries. We are in urgent need of finding an effective therapy but also a valid prophylactic means of preventing AD. There is a growing attention currently paid to DNA vaccination, a technology particularly used during the COVID-19 era, which can be used also to potentially prevent or modify the course of neurological diseases, including AD. This paper aims to discuss the main features and hurdles encountered in the immunization and therapy against AD using DNA vaccine technology. Ultimately, this work aims to effectively promote the efforts in research for the development of safe and effective DNA and RNA vaccines for AD. Full article

Breakthrough infections in SARS-CoV-2 vaccinated individuals are an ideal circumstance for the simultaneous exploration of both the vaccine-induced memory reaction to the spike (S) protein and the primary response to the membrane (M) and nucleocapsid (N) proteins generated by natural infection. We monitored 15 healthcare workers who had been vaccinated with two doses of Pfizer BioNTech BNT162b2 and were then later infected with the SARS-CoV-2 B.1.617.2. (Delta) variant, analysing the antiviral humoral and cellular immune responses. Natural infection determined an immediate and sharp rise in anti-RBD antibody titres and in the frequency of both S-specific antibody secreting cells (ASCs) and memory B lymphocytes. T cells responded promptly to infection by activating and expanding already at 2–5 days. S-specific memory and emerging M- and N-specific T cells both expressed high levels of activation markers and showed effector capacity with similar kinetics but with different magnitude. The results show that natural infection with SARS-CoV-2 in vaccinated individuals induces fully functional and rapidly expanding T and B lymphocytes in concert with the emergence of novel virus-specific T cells. This swift and punctual response also covers viral variants and captures a paradigmatic case of a healthy adaptive immune reaction to infection with a mutating virus. Full article

Vaccination is a groundbreaking approach in preventing and controlling infectious diseases. However, the effectiveness of vaccines can be greatly enhanced by the inclusion of adjuvants, which are substances that potentiate and modulate the immune response. This review is based on extensive searches in reputable databases such as Web of Science, PubMed, EMBASE, Scopus, and Google Scholar. The goal of this review is to provide a thorough analysis of the advances in the field of adjuvant research, to trace the evolution, and to understand the effects of the various adjuvants. Historically, alum was the pioneer in the field of adjuvants because it was the first to be approved for use in humans. It served as the foundation for subsequent research and innovation in the field. As science progressed, research shifted to identifying and exploiting the potential of newer adjuvants. One important area of interest is nano formulations. These advanced adjuvants have special properties that can be tailored to enhance the immune response to vaccines. The transition from traditional alum-based adjuvants to nano formulations is indicative of the dynamism and potential of vaccine research. Innovations in adjuvant research, particularly the development of nano formulations, are a promising step toward improving vaccine efficacy and safety. These advances have the potential to redefine the boundaries of vaccination and potentially expand the range of diseases that can be addressed with this approach. There is an optimistic view of the future in which improved vaccine formulations will contribute significantly to improving global health outcomes. Full article

The placental transfer of antibodies that mediate bacterial clearance via phagocytes is likely important for protection against invasive group B Streptococcus (GBS) disease. A robust functional assay is essential to determine the immune correlates of protection and assist vaccine development. Using standard reagents, we developed and optimized an opsonophagocytic killing assay (OPKA) where dilutions of test sera were incubated with bacteria, baby rabbit complement (BRC) and differentiated HL60 cells (dHL60) for 30 min. Following overnight incubation, the surviving bacteria were enumerated and the % bacterial survival was calculated relative to serum-negative controls. A reciprocal 50% killing titer was then assigned. The minimal concentrations of anti-capsular polysaccharide (CPS) IgG required for 50% killing were 1.65–3.70 ng/mL (depending on serotype). Inhibition of killing was observed using sera absorbed with homologous CPS but not heterologous CPS, indicating specificity for anti-CPS IgG. The assay performance was examined in an interlaboratory study using residual sera from CPS-conjugate vaccine trials with international partners in the Group B Streptococcus Assay STandardisatiON (GASTON) Consortium. Strong correlations of reported titers between laboratories were observed: ST-Ia r = 0.88, ST-Ib r = 0.91, ST-II r = 0.91, ST-III r = 0.90 and ST-V r = 0.94. The OPKA is an easily transferable assay with accessible standard reagents and will be a valuable tool to assess GBS-specific antibodies in natural immunity and vaccine studies. Full article