Vaccines, Volume 12, Issue 1 (January 2024) – 108 articles

Since the 2000s, sporadic outbreaks of whooping cough have been reported in advanced countries, where the acellular pertussis vaccination rate is relatively high, and in developing countries. Small-scale whooping cough has also continued in many countries, due in part to the waning of immune protection after childhood vaccination, necessitating the development of an improved pertussis vaccine and vaccination program. Currently, two different production platforms are being actively pursued in Korea; one is based on the aP (acellular pertussis) vaccine purified from B. pertussis containing pertussis toxoid (PT), filamentous hemagglutin (FHA) and pertactin (PRN), and the other is based on the recombinant aP (raP), containing genetically detoxified pertussis toxin ADP-ribosyltransferase subunit 1 (PtxS1), FHA, and PRN domain, expressed and purified from recombinant E. coli. aP components were further combined with diphtheria and tetanus vaccine components as a prototype DTaP vaccine by GC Pharma (GC DTaP vaccine). We evaluated and compared the immunogenicity and the protective efficacy of aP and raP vaccines in an experimental murine challenge model: humoral immunity in serum, IgA secretion in nasal lavage, bacterial clearance after challenge, PTx (pertussis toxin) CHO cell neutralization titer, cytokine secretion in spleen single cell, and tissue resident memory CD4+ T cell (CD4+ T_RM cell) in lung tissues. In humoral immunogenicity, GC DTaP vaccines showed high titers for PT and PRN and showed similar patterns in nasal lavage and IL-5 cytokine secretions. The GC DTaP vaccine and the control vaccine showed equivalent results in bacterial clearance after challenge, PTx CHO cell neutralization assay, and CD4+ T_RM cell. In contrast, the recombinant raP vaccine exhibited strong antibody responses for FHA and PRN, albeit with low antibody level of PT and low titer in PTx CHO neutralization assay, as compared to control and GC DTaP vaccines. The raP vaccine provided a sterile lung bacterial clearance comparable to a commercial control vaccine after the experimental challenge in murine model. Moreover, raP exhibited a strong cytokine response and CD4+ T_RM cell in lung tissue, comparable or superior to the experimental and commercial DTaP vaccinated groups. Contingent on improving the biophysical stability and humoral response to PT, the raP vaccine warrants further development as an effective alternative to aP vaccines for the control of a pertussis outbreak. Full article

Measles is targeted for elimination since 2001, with a significant reduction in cases recorded worldwide, but outbreaks occur periodically due to immunization gaps. This study analyzes the evolution of vaccination coverage rates (VCRs) in Romania, a EU country with large measles epidemics during the last two decades, including an ongoing outbreak in 2023. Vaccination against measles has been part of the National Immunization Program since 1979, initially as a single dose, and from 1994 onwards it has had two doses. The initially high national VCRs of >97% gradually declined from 2010 onward and remained constantly under 90%, with further decreases during the COVID-19 pandemic. The lowest VCRs for both vaccine doses in the last decade were recorded in 2022 and were 83.4% for the first dose and 71.4% for the second dose, with significant differences among Romania’s 42 counties. Several factors contributed to this decline, including failure to attend the general practitioners’ offices, increased number of children lost to follow-up due to population movements, missed vaccination opportunities due to temporary medical contraindications, a surge in vaccine hesitancy/refusal, a decreasing number of general practitioners and discontinuities in vaccine supply. The persisting suboptimal VCRs in Romania threaten the progress toward measles elimination. Full article

Four mutants varying the length of the G and SH genes, including a G-truncated mutant (ΔG) and three G/SH-truncated mutants (ΔSH/G-1, ΔSH/G-2, and ΔSH/G-3), were generated via serially passaging the avian metapneumovirus strain SNU21004 into the cell lines Vero E6 and DF-1 and into embryonated chicken eggs. The mutant ΔG particles resembled parental virus particles except for the variance in the density of their surface projections. G and G/SH truncation significantly affected the viral replication in chickens’ tracheal ring culture and in infected chickens but not in the Vero E6 cells. In experimentally infected chickens, mutant ΔG resulted in the restriction of viral replication and the attenuation of the virulence. The mutants ΔG and ΔSH/G-1 upregulated three interleukins (IL-6, IL-12, and IL-18) and three interferons (IFNα, IFNβ, and IFNγ) in infected chickens. In addition, the expression levels of innate immunity-related genes such as Mda5, Rig-I, and Lgp2, in BALB/c mice were also upregulated when compared to the parental virus. Immunologically, the mutant ΔG induced a strong, delayed humoral immune response, while the mutant ΔSH/G-1 induced no humoral immune response. Our findings indicate the potential of the mutant ΔG but not the mutant ΔSH/G-1 as a live attenuated vaccine candidate. Full article

Tick-borne encephalitis (TBE) is a serious neurological disease caused by TBE virus (TBEV). Because antiviral treatment options are not available, vaccination is the key prophylactic measure against TBEV infections. Despite the availability of effective vaccines, cases of vaccination breakthrough infections have been reported. The multienzymatic non-structural protein 3 (NS3) of orthoflaviviruses plays an important role in polyprotein processing and virus replication. In the present study, we evaluated NS3 of TBEV as a potential vaccine target for the induction of protective immunity. To this end, a recombinant modified vaccinia virus Ankara that drives the expression of the TBEV NS3 gene (MVA-NS3) was constructed. MVA-NS3 was used to immunize C57BL/6 mice. It induced NS3-specific immune responses, in particular T cell responses, especially against the helicase domain of NS3. However, MVA-NS3-immunized mice were not protected from subsequent challenge infection with a lethal dose of the TBEV strain Neudoerfl, indicating that in contrast to immunity to prME and NS1, NS3-specific immunity is not an independent correlate of protection against TBEV in this mouse model. Full article

Vaccination provides the best protection against the increasing infections of SARS-CoV-2. The magnitude and type of anti-SARS-CoV-2 vaccine side effects (SEs) depend on parameters that are not fully understood. In this cross-sectional study, the associations between different anti-SARS-CoV-2 vaccine SEs and age, sex, the presence of chronic diseases, medication intake, history of allergies, and infections with SARS-CoV-2 were investigated. Our survey used the Google platform and had 866 participants, contacted through e-mails, social media and chain referral sampling (margin of error ≈ 4.38%, 99% confidence). More than 99% of the participants received the BNT162b2 and ChAdOx1-S vaccines. Being female, having chronic diseases, taking medicines routinely and the presence of a SARS-CoV-2 infection (p < 0.05) were associated with strong SEs after the BNT162b2 vaccine second dose. Having a history of allergies and a female sex (p < 0.01) were associated with strong SEs after the ChAdOx1-S vaccine second dose. Furthermore, the results reveal, for the first time, the associations between having a history of allergies, chronic diseases, medication usage, and SEs of a strong magnitude for the BNT162b2 and ChAdOx1-S vaccines. Additionally, this study supports the association of the female sex and infection with SARS-CoV-2 with an increased potential of developing stronger SEs with certain anti-SARS-CoV-2 vaccines. Full article

The COVID-19 pandemic led to the rapid and worldwide development of highly effective vaccines against SARS-CoV-2. However, there is significant individual-to-individual variation in vaccine efficacy due to factors including viral variants, host age, immune status, environmental and host genetic factors. Understanding those determinants driving this variation may inform the development of more broadly protective vaccine strategies. While host genetic factors are known to impact vaccine efficacy for respiratory pathogens such as influenza and tuberculosis, the impact of host genetic variation on vaccine efficacy against COVID-19 is not well understood. To model the impact of host genetic variation on SARS-CoV-2 vaccine efficacy, while controlling for the impact of non-genetic factors, we used the Diversity Outbred (DO) mouse model. We found that DO mice immunized against SARS-CoV-2 exhibited high levels of variation in vaccine-induced neutralizing antibody responses. While the majority of the vaccinated mice were protected from virus-induced disease, similar to human populations, we observed vaccine breakthrough in a subset of mice. Importantly, we found that this variation in neutralizing antibody, virus-induced disease, and viral titer is heritable, indicating that the DO serves as a useful model system for studying the contribution of genetic variation of both vaccines and disease outcomes. Full article

During the coronavirus diseases 2019 (COVID-19) pandemic, the safety and efficacy of vaccination during pregnancy, particularly regarding the risk of preterm birth, have been a subject of concern. This systematic review aims to evaluate the impact of COVID-19 vaccination on preterm birth risk and to inform clinical practice and public health policies. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a database search included PubMed, Embase, and Scopus, conducted up until October 2023. Inclusion criteria focused on studies that examined COVID-19 vaccination during pregnancy and its correlation with preterm birth, defined as a birth before 37 weeks of gestation. Six studies met these criteria, encompassing 35,612 patients. A quality assessment was performed using the Newcastle–Ottawa Scale and the Cochrane Collaboration’s tool, with the risk of bias evaluated via a funnel plot analysis and an Egger’s regression test. The studies demonstrated geographical diversity, mainly from Israel, Romania, and the United States, with a blend of prospective and retrospective designs. The patient cohort’s mean age was 31.2 years, with common comorbidities such as gestational diabetes and obesity affecting 9.85% of the total population. The vaccination types varied across the studies, with BNT162b2 being the most used. The results indicated a low heterogeneity among the included studies, evidenced by a Cochran’s Q statistic of 2.10 and an I² statistic of 13%. The meta-analysis yielded a pooled odds ratio (OR) for a preterm birth risk post-vaccination of approximately 1.03 (95% CI: 0.82–1.30), suggesting no significant increase in preterm birth risk was associated with COVID-19 vaccination. Notable findings included a low preterm birth rate (as low as 0.6% and up to 6.1%) with minimal differences in neonatal outcomes, such as birth weight and APGAR (appearance, pulse, grimace, activity, and respiration) scores between vaccinated and unvaccinated groups. This study concludes that a COVID-19 vaccination during pregnancy does not significantly increase the risk of preterm birth. These findings are crucial for reassuring healthcare providers and pregnant women about the safety of COVID-19 vaccines and supporting their use in public health strategies during the pandemic. Full article

Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan that can elicit a robust immune response during infection. Macrophage cells have been shown to play an important role in the immune response against T. gondii. In our previous study, the eukaryotic translation initiation factor 5A (eIF-5A) gene of T. gondii was found to influence the invasion and replication of tachyzoites. In this study, the recombinant protein of T. gondii eIF-5A (rTgeIF-5A) was incubated with murine macrophages, and the regulatory effect of TgeIF-5A on macrophages was characterized. Immunofluorescence assay showed that TgeIF-5A was able to bind to macrophages and partially be internalized. The Toll-like receptor 4 (TLR4) level and chemotaxis of macrophages stimulated with TgeIF-5A were reduced. However, the phagocytosis and apoptosis of macrophages were amplified by TgeIF-5A. Meanwhile, the cell viability experiment indicated that TgeIF-5A can promote the viability of macrophages, and in the secretion assays, TgeIF-5A can induce the secretion of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and nitric oxide (NO) from macrophages. These findings demonstrate that eIF-5A of T. gondii can modulate the immune response of murine macrophages in vitro, which may provide a reference for further research on developing T. gondii vaccines. Full article

We have developed Convacell^®—a COVID-19 vaccine based on the recombinant nucleocapsid (N) protein of SARS-CoV-2. This paper details Convacell’s^® combined phase I/II and IIb randomized, double-blind, interventional clinical trials. The primary endpoints were the frequency of adverse effects (AEs) and the titers of specific anti-N IgGs induced by the vaccination; secondary endpoints included the nature of the immune response. Convacell^® demonstrated high safety in phase I with no severe AEs detected, 100% seroconversion by day 42 and high and sustained for 350 days anti-N IgG levels in phase II. Convacell^® also demonstrated a fused cellular and humoral immune response. Phase IIb results showed significant post-vaccination increases in circulating anti-N IgG and N protein-specific IFNγ⁺-producing PBMC quantities among 438 volunteers. Convacell^® showed same level of immunological efficacy for single and double dose vaccination regimens, including for elderly patients. The clinical studies indicate that Convacell^® is safe and highly immunogenic. Full article

Long COVID and its symptoms have not been examined in different subpopulations of U.S. adults. Using the 2022 BRFSS (n = 445,132), we assessed long COVID and each symptom by sociodemographic characteristics and health-related variables. Multivariable logistic regression was conducted to examine factors associated with long COVID and the individual symptoms. Prevalence differences were conducted to examine differences in long COVID by vaccination status. Overall, more than one in five adults who ever had COVID-19 reported symptoms consistent with long COVID (21.8%). The most common symptom was tiredness or fatigue (26.2%), followed by difficulty breathing or shortness of breath (18.9%), and loss of taste or smell (17.0%). Long COVID was more common among adults under 65 years, women, American Indian or Alaska Native or other/multi race group, smokers, and people with a disability, depression, overweight or obesity compared to their respective counterparts. The prevalence of long COVID was higher among unvaccinated adults (25.6%) than vaccinated adults (21.6%) overall, and for 20 of 32 subgroups assessed. These findings underscore the benefits of vaccination, the importance of early treatment, and the need to better inform health care resource allocation and support services for those experiencing long COVID. Full article

With the worldwide spread of SARS-CoV-2 disease, people with cystic fibrosis (CF), especially solid organ transplant recipients, have quickly been identified as a risk group for severe disease. Studies have shown low antibody response to SARS-CoV-2 vaccines in recipients of solid organ transplant compared to the healthy population. Information on immune response in CF patients with solid organ transplantation is limited, especially regarding long-term efficacy. The aim of this real-world study was a long-term assessment of humoral immune response induced by three and four doses of the SARS-CoV-2 mRNA vaccine. S1RBD and IgG antibodies were measured every 12 weeks over a period of 27 months in twelve CF patients (five liver and seven lung transplantation recipients). A total of 83.3% of our patients showed a positive antibody response after three doses of the SARS-CoV-2 mRNA vaccine. A sustained immune response was observed in both groups over the observation period, with liver transplant recipients showing higher levels than lung transplant recipients. This study is among the first to show long-term data with constantly elevated or even increasing antibody levels. We conclude that this effect is most likely associated with repeated boostering in terms of infections and booster vaccinations. Full article

Respiratory Syncytial Virus (RSV) poses a significant global health concern as a major cause of lower respiratory tract infections (LRTIs). Over the last few years, substantial efforts have been directed towards developing vaccines and therapeutics to combat RSV, leading to a diverse landscape of vaccine candidates. Notably, two vaccines targeting the elderly and the first maternal vaccine have recently been approved. The majority of the vaccines and vaccine candidates rely solely on a prefusion-stabilized conformation known for its highly neutralizing epitopes. Although, so far, this antigen design appears to be successful for the elderly, our current understanding remains incomplete, requiring further improvement and refinement in this field. Pediatric vaccines still have a long journey ahead, and we must ensure that vaccines currently entering the market do not lose efficacy due to the emergence of mutations in RSV’s circulating strains. This review will provide an overview of the current status of vaccine designs and what to focus on in the future. Further research into antigen design is essential, including the exploration of the potential of alternative RSV proteins to address these challenges and pave the way for the development of novel and effective vaccines, especially in the pediatric population. Full article

In North America, range constraints due to burgeoning development increasingly encroach on wild horse habitat and necessitate effective but humane reproductive management. The largest free-roaming wild horse fertility control program by population (>3500) and territory size (≈300,000 acres) is located within Nevada’s Virginia Range. Data from a field study investigated porcine zona pellucida (pZP) immunocontraception via remote dart delivery to mares in this population. Analyses aimed to measure efficacy by treatment effects on annual birth rates and population demographics and to evaluate treatment frequency and season against these variables. Analyses included mares’ monthly data (January 2019–December 2022; 48 months), characterized by cumulative vaccination numbers subset into four classifications considering the vaccine as having no loss of efficacy or a loss within a 6-, 12-, and 18-month period post vaccination; from foaling data, the likelihood of being in foal and of conceiving in that month; and from age, as mature or immature (<1 years-old). A downward foaling rate and trend in the numbers of mature mares, descriptively presented at monthly intervals, showed markedly declining annual seasonal breeding peaks, with no observed change in foaling season or duration. Within four years, population coverage surpassed 70% and was associated with a 58% reduction in foaling, with only a 10% conception rate. Vaccinated mares increased proportionally: assuming a 12-month decay rate, the system reached stability at an average ≈1.0 vaccination/mare/year, providing a robust recommendation for treatment frequency contributing to best management practices. Full article

Background: Influenza viruses continue to cause a significant social and economic burden globally. Vaccination is recognized as the most effective measure to control influenza. Live attenuated influenza vaccines (LAIVs) are an effective means of preventing influenza, especially among children. A reverse genetics (RG) system is required to rapidly update the antigenic composition of vaccines, as well as to design LAIVs with a broader spectrum of protection. Such a system has been developed for the Russian LAIVs only for type A strains, but not for influenza B viruses (IBV). Methods: All genes of the B/USSR/60/69 master donor virus (B60) were cloned into RG plasmids, and the engineered B60, as well as a panel of IBV LAIV reassortants were rescued from plasmid DNAs encoding all viral genes. The engineered viruses were evaluated in vitro and in a mouse model. Results: The B60 RG system was successfully developed, which made it possible to rescue LAIV reassortants with the desired antigenic composition, including hybrid strains with hemagglutinin and neuraminidase genes belonging to the viruses from different IBV lineages. The LAIV candidate carrying the HA of the B/Victoria-lineage virus and NA from the B/Yamagata-lineage virus demonstrated optimal characteristics in terms of safety, immunogenicity and cross-protection, prompting its further assessment as a broadly protective component of trivalent LAIV. Conclusions: The new RG system for B60 MDV allowed the rapid generation of type B LAIV reassortants with desired genome compositions. The generation of hybrid LAIV reassortants with HA and NA genes belonging to the opposite IBV lineages is a promising approach for the development of IBV vaccines with broad cross-protection. Full article

The capability of antibodies to neutralize different SARS-CoV-2 variants varies among individuals depending on the previous exposure to wild-type or Omicron-specific immunogens by mono- or bivalent vaccinations or infections. Such profiles of neutralizing antibodies (nAbs) usually have to be assessed via laborious live-virus neutralization tests (NTs). We therefore analyzed whether a novel multivariant surrogate-virus neutralization test (sVNT) (adapted from a commercial microarray) that quantifies the antibody-mediated inhibition between the receptor angiotensin-converting enzyme 2 (ACE2) and variant-specific receptor-binding domains (RBDs) can assess the neutralizing activity against the SARS-CoV-2 wild-type, and Delta Omicron BA.1, BA.2, and BA.5 subvariants after a booster with Omicron-adapted bivalent vaccines in a manner similar to live-virus NTs. Indeed, by using the live-virus NTs as a reference, we found a significant correlation between the variant-specific NT titers and levels of ACE2-RBD binding inhibition (p < 0.0001, r ≤ 0.78 respectively). Furthermore, the sVNTs identified higher inhibition values against BA.5 and BA.1 in individuals vaccinated with Omicron-adapted vaccines than in those with monovalent wild-type vaccines. Our data thus demonstrate the ability of sVNTs to detect variant-specific nAbs following a booster with bivalent vaccines. Full article

Pharmacists are well-positioned to help increase pediatric immunization rates. This study assessed the types of pediatric vaccines offered in community pharmacies, compared participant/pharmacy characteristics and participants’ perceptions of barriers and pharmacists’ role in providing pediatric immunizations between pharmacy-based providers and non-providers, and assessed factors associated with pharmacy-based pediatric immunization provision. A cross-sectional survey was sent to Alabama community pharmacies from February to April 2023, of which 240 responded (20.5% response rate). Measures included whether they offered childhood vaccines in 2022 and the types of vaccines administered, participants’ perceptions of pharmacists’ role in pediatric immunization, and perceived barriers to providing pharmacy-based pediatric immunizations. Roughly half of pharmacies (50.8%) provided pediatric immunization services with influenza vaccines (91.0%) the most commonly provided vaccines and poliovirus-inactivated vaccines (4.9%) the least. Pharmacies providing pediatric immunization services significantly differed from non-providers. That is, the majority of providers practiced within a grocery or retail store; they were younger and practiced in a pharmacy with higher average daily prescription volume and a higher average pharmacy practice full-time equivalent; and they perceived lower implementation logistics barriers and a lower role of pharmacists regarding pediatric immunization. Multivariable logistic regression analysis indicated that implementation logistics is significantly associated with pharmacies offering pediatric immunization services after controlling for pharmacy/participant characteristics (p = 0.01). Therefore, ameliorating implementation logistics barriers should be considered when devising strategies to promote pediatric immunization services in community pharmacies. Full article

Dengue virus is an enveloped virus with an icosahedral assembly of envelope proteins (E). The E proteins are arranged as a head-to-tail homodimer, and domain III (EDIII) is placed at the edge of the dimer, converging to a pentamer interface. For a structure-based approach, cholera toxin B (CTB) was harnessed as a structural scaffold for the five-fold symmetry of EDIII. Pivoted by an RNA-mediated chaperone for the protein folding and assembly, CTB-EDIII of dengue serotype 1 (DV1) was successfully produced as soluble pentamers in an E. coli host with a high yield of about 28 mg/L. Immunization of mice with CTB-DV1EDIII elicited increased levels of neutralizing antibodies against infectious viruses compared to the control group immunized with DV1EDIII without CTB fusion. IgG isotype switching into a balanced Th1/Th2 response was also observed, probably triggered by the intrinsic adjuvant activity of CTB. Confirming the immune-enhancing potential of CTB in stabilizing the pentamer assembly of EDIII, this study introduces a low-cost bacterial production platform designed to augment the soluble production of subunit vaccine candidates, particularly those targeting flaviviruses. Full article

Immunosuppressed kidney transplant (KT) recipients produce a weaker response to COVID-19 vaccination than immunocompetent individuals. We tested antiviral IgG response in 99 KT recipients and 66 healthy volunteers who were vaccinated with mRNA-1273 Moderna or BNT162b2 Pfizer-BioNTech vaccines. A subgroup of participants had their peripheral blood leukocytes (PBLs) evaluated for the frequency of T helper 1 (Th1) cells producing IL-2, IFN-γ and/or TNF-α, and IL-10-producing T-regulatory 1 (Tr) cells. Among KT recipients, 45.8% had anti-SARS-CoV-2 IgG compared to 74.1% of healthy volunteers (p = 0.009); also, anti-viral IgG levels were lower in recipients than in volunteers (p = 0.001). In terms of non-responders (≤2000 U/mL IgG), Moderna’s group had 10.8% and Pfizer-BioNTech’s group had 34.3% of non-responders at 6 months (p = 0.023); similarly, 15.7% and 31.3% were non-responders in Moderna and Pfizer-BioNTech groups at 12 months, respectively (p = 0.067). There were no non-responders among controls. Healthy volunteers had higher Th1 levels than KT recipients, while Moderna produced a higher Th1 response than Pfizer-BioNTech. In contrast, the Pfizer-BioNTech vaccine induced a higher Tr1 response than the Moderna vaccine (p < 0.05); overall, IgG levels correlated with Th1(fT_TNF-α)/Tr1(fT_IL-10) ratios. We propose that the higher number of non-responders in the Pfizer-BioNTech group than the Moderna group was caused by a more potent activity of regulatory Tr1 cells in KT recipients vaccinated with the Pfizer-BioNTech vaccine. Full article

Endemic human coronaviruses (HCoV) NL63, 229E, OC43, and HKU1 cause respiratory infection. Following infection, a virus-specific serum antibody rise is usually observed, coinciding with recovery. In some cases, an infection is not accompanied by an immunoglobulin G (IgG) antibody rise in serum in the first month after HCoV infection, even though the infection has cleared in that month and the patient has recovered. We investigated the possible role of nasal immunoglobulin A (IgA). We measured spike (S) and nucleocapsid (N)-specific nasal IgA during and after an HCoV lower respiratory tract infection (LRTI) and compared the IgA responses between subjects with and without a significant IgG rise in serum (IgG responders (n = 31) and IgG non-responders (n = 14)). We found that most IgG responders also exhibited significant nasal IgA rise in the first month after the infection, whereas such an IgA rise was lacking in most IgG non-responders. Interestingly, the serum IgG non-responders presented with a significantly higher nasal IgA when they entered this study than during the acute phase of the LRTI. Our data suggest that nasal IgA could be part of a fast acute response to endemic HCoV infection and may play a role in clearing the infection. Full article

Background: The eradication of poliovirus and improving routine immunization (RI) coverage rates present significant challenges in Pakistan. There is a need for interventions that focus on strengthening community engagement to improve routine immunization coverage. Our primary objective is to assess the impact of an integrated strategy designed to enhance community engagement and maternal and child health immunization campaigns on immunization coverage in Pakistan’s high-risk union councils of polio-endemic districts. Method: We implemented an integrated approach for routine immunization and maternal and child health in the polio-endemic district of Pakistan. This approach involved setting up health camps and actively engaging and mobilizing the local community. An independent team conducted surveys at three key points: baseline, midline, and endline, to evaluate immunization coverage among children under the age of five. The primary outcome measures for the study were coverage of OPV, IPV, and changes in the proportion of unvaccinated and fully vaccinated children. To select clusters and eligible households in each cluster, we utilized a 30 × 15 cluster sampling technique. Multivariable associations between socio-demographic factors and changes in the proportion of fully vaccinated children at the UC level were assessed using hierarchical linear regression models. Results: A total of 256,946 children under the age of five (122,950 at baseline and 133,996 at endline) were enrolled in the study. By the endline, full immunization coverage had increased to 60% or more in all three study areas compared to the baseline. Additionally, there was a significant increase in the coverage of both OPV and IPV across all three provinces at the endline. The full immunization rates were assessed on three levels of the framework: the distal, intermediate (access and environment), and proximal level (camp attendance and effectiveness). At the distal level, on multivariate analysis, family size was found to be a significant predictor of change in immunity within the families (β = 0.68; p ≤ 0.0001). At the intermediate level, the likelihood of full immunization decreased with the decrease in knowledge about vaccination (β = −0.38; p = 0.002), knowledge about polio vaccine (β = −0.25; p = 0.011), and knowledge about IPV (β = −0.06; p = 0.546). Perceived obstacles to vaccination were fear of adverse events (β = −0.4; p ≤ 0.0001) and lack of education (β = 0.23; p = 0.031), which were found to be significant in bivariate and multivariate analyses. At the proximal level, community mobilization (β = 0.26; p = 0.008) and attendance at health camp (β = 0.21; p ≤ 0.0001) were found to enhance full immunization coverage. On the other hand, the most prominent reason for not attending health camp included no need to attend the health camp as the child was not ill (β = −0.13; p = 0.008). Conclusions: This study found that community mobilization and attendance at health camps significantly enhanced full immunization coverage. The findings highlight the importance of community engagement and targeted interventions in improving immunization coverage and addressing barriers to healthcare seeking. Full article

Abdominal obesity is highly prevalent in Mexico and has a poor prognosis in terms of the severity of coronavirus disease (COVID-19) and low levels of antibodies induced by infection and vaccination. We evaluated the humoral immune response induced by COVID-19 and five different vaccination schedules in Mexican individuals with abdominal obesity and the effects of other variables. This prospective longitudinal cohort study included 2084 samples from 389 participants. The levels of anti-S1/S2 and anti-RBD IgG antibodies were measured at various time points after vaccination. A high prevalence of hospitalization and oxygen use was observed in individuals with abdominal obesity (AO) who had COVID-19 before vaccination; however, they also had high levels of anti-S1/S2 and anti-RBD-neutralizing IgG antibodies. The same was true for vaccination-induced antibody levels. However, their longevity was low. Interestingly, we did not observe significant differences in vaccine reactogenicity between abdominally obese and abdominally non-obese groups. Finally, individuals with a higher body mass index, older age, and previous COVID-19 had higher levels of antibodies induced by COVID-19 and vaccination. Therefore, it is important to evaluate other immunological and inflammatory factors to better understand the pathogenesis of COVID-19 in the presence of risk factors and to propose effective vaccination schedules for vulnerable populations. Full article

Among emergent climate-sensitive infectious diseases, some mosquito-vectored arbovirus infections have epidemiological, social, and economic effects. Dengue virus (DENV), West Nile virus (WNV), and Chikungunya virus (CHIKV) disease, previously common only in the tropics, currently pose a major risk to global health and are expected to expand dramatically in the near future if adequate containment measures are not implemented. The lack of safe and effective vaccines is critical as it seems likely that emerging mosquito-vectored arbovirus infections will be con-trolled only when effective and safe vaccines against each of these infections become available. This paper discusses the clinical characteristics of DENV, WNV, and CHIKV infections and the state of development of vaccines against these viruses. An ideal vaccine should be able to evoke with a single administration a prompt activation of B and T cells, adequate concentrations of protecting/neutralizing antibodies, and the creation of a strong immune memory capable of triggering an effective secondary antibody response after new infection with a wild-type and/or mutated infectious agent. Moreover, the vaccine should be well tolerated, safe, easily administrated, cost-effective, and widely available throughout the world. However, the development of vaccines against emerging mosquito-vectored arbovirus diseases is far from being satisfactory, and it seems likely that it will take many years before effective and safe vaccines for all these infections are made available worldwide. Full article

Monocytes (Mos) are believed to play important roles during the generation of immune response. In our previous study, CVC1302, a complex of PRRs agonists, was demonstrated to recruit Mo into lymph nodes (LNs) in order to present antigen and secret chemokines (CXCL9 and CXCL10), which attracted antigen-specific CD4⁺ T cells. As it is known that Mos in mice are divided into two main Mo subsets (Ly6C⁺ Mo and Ly6C⁻ Mo), we aimed to clarify the CVC1302-recruiting Mo subset and functions in the establishment of immunity. In this study, we found that CVC1302 attracted both Ly6C⁺ Mo and Ly6C⁻ Mo into draining LNs, which infiltrated from different origins, injection muscles and high endothelial venule (HEV), respectively. We also found that the numbers of OVA⁺ Ly6C⁺ Mo in the draining LNs were significantly higher compared with OVA⁺ Ly6C⁻ Mo. However, the levels of CXCL9 and CXCL10 produced by Ly6C⁻ Mo were significantly higher than Ly6C⁺ Mo, which plays important roles in attracting antigen-specific CD4⁺ T cells. Under the analysis of their functions in initiating immune responses, we found that the ability of the Ly6C⁺ monocyte was mainly capturing and presenting antigens, otherwise; the ability of the Ly6C⁻ monocyte was mainly secreting CXCL9 and CXCL10, which attracted antigen-specific CD4⁺ T cells through CXCR3. These results will provide new insights into the development of new immunopotentiators and vaccines. Full article

The data on the risk of herpes zoster (HZ) in spondyloarthropathy (SpA) patients are sparse, especially regarding its association with the novel mRNA COVID-19 vaccines and immunosuppressants. We aimed to evaluate whether SpA diagnosis and/or immunosuppressant use affect HZ risk and the influence of mRNA COVID-19 vaccination. We assessed the association between SpA (psoriatic arthritis (PsA) and ankylosing spondylitis (AS)) diagnoses and HZ in a large population database with patients matched by age and sex to controls. We also assessed the association between the COVID-19 vaccine and new-onset HZ using two nested case–control studies, identifying all new HZ cases diagnosed from 1 January–31 December 2021 within the SpA and general population cohorts, matched randomly by sex, age and HZ index date to controls without HZ. Exposure to mRNA COVID-19 vaccination was ascertained in the 6 weeks prior to the index date both in cases and controls. In our results, the incidence rate of HZ was higher in PsA patients vs. the general population, at 1.03 vs. 0.64 per 100 person-years, respectively (adjusted HR = 1.55; 95%CI, 1.19–2.02). Within the SpA group, Jak-I treatment was associated with a higher risk of developing new-onset HZ (adjusted OR = 3.79; 1.15–12.5). Multivariable conditional logistic regression models we used showed no association between COVID-19 vaccination and new-onset HZ among the SpA patients (OR = 1.46; 0.68–3.14). Full article

Human papillomavirus (HPV) vaccine uptake among adolescent girls is critical to reducing the burden of HPV-related cancers in Nigeria. This study assesses the factors influencing caregivers’ acceptance of HPV vaccination for their charges, using the Fogg Behavior Model (FBM) as a theoretical framework. We analyzed cross-sectional data from 1429 caregivers of girls aged 9–17 in six Nigerian states, using a survey instrument based on the FBM. Participants were recruited via Facebook and Instagram advertisements and interviewed through Facebook Messenger in August and September 2023. The study received ethical clearance from Nigeria’s National Health Research Ethics Committee. We applied bivariate and multivariate analyses to assess the relationships between the caregiver’s perception of how likely their adolescent girl was to get vaccinated in the next 12 months and motivation, ability, social factors (such as discussions with family and friends), injunctive norms, previous COVID-19 vaccination, and respondents’ sociodemographic characteristics. Adjusted odds ratios derived from logistic regression analyses revealed that caregivers’ motivation and ability, as well as social factors, were significantly associated with their perception that the adolescent girl in their care would get vaccinated within the next 12 months. Our findings suggest that behavioral interventions tailored to enhance motivation, ability, and social support among caregivers could significantly increase HPV vaccine uptake among adolescent girls in Nigeria. Full article

As SARS-CoV-2 variants continue to emerge, vaccination remains a critical tool to reduce the COVID-19 burden. Vaccine reactogenicity and the impact on work productivity/daily activities are recognized as contributing factors to vaccine hesitancy. To encourage continued COVID-19 vaccination, a more complete understanding of the differences in reactogenicity and impairment due to vaccine-related side effects across currently available vaccines is necessary. The 2019nCoV-406 study (n = 1367) was a prospective observational study of reactogenicity and associated impairments in adults in the United States and Canada who received an approved/authorized COVID-19 vaccine. Compared with recipients of mRNA COVID-19 booster vaccines, a smaller percentage of NVX-CoV2373 booster recipients reported local and systemic reactogenicity. This study’s primary endpoint (percentage of participants with ≥50% overall work impairment on ≥1 of the 6 days post-vaccination period) did not show significant differences. However, the data suggest that NVX-CoV2373 booster recipients trended toward being less impaired overall than recipients of an mRNA booster; further research is needed to confirm this observed trend. The results of this real-world study suggest that NVX-CoV2373 may be a beneficial vaccine option with limited impact on non-work activities, in part due to the few reactogenicity events after vaccination. Full article

The growing use of biological drugs in immune-mediated chronic diseases has undoubtedly revolutionized their treatment. Yet, the topic of vaccinations in this group of patients still raises many concerns and implies many therapeutic problems that require discussion and standardization of management. The aim of this literature review is to present current knowledge regarding safety and efficacy of vaccinations in dermatological and rheumatological patients treated with biological drugs and JAK inhibitors. Additionally, this article provides recommendation from experts of the Polish Dermatological Society about proper use of vaccinations during therapy with biologics. Generally, all live attenuated vaccines are contraindicated during immunosuppressive/immunomodulatory therapy. If there is need, they should be administered long enough prior to the therapy or after cessation. Yet, inactivated vaccines mostly can be safely used, but the problem in this case is the effectiveness of the vaccination. Most studies report that the immune response in patients on biologics after administration of different inactivated vaccines is similar to or even better than in the control group. Thus, the importance of vaccination among patients on biologics must be emphasized to reduce omissions and the fear of possible side effects or insufficient post-vaccination response. Full article

Since late 2019, most efforts to control the COVID-19 pandemic have focused on developing vaccines. By mid-2020, some vaccines fulfilled international regulations for their application. However, these vaccines have shown a decline in effectiveness several weeks after the last dose, highlighting the need to optimize vaccine administration due to supply chain limitations. While methods exist to prioritize population groups for vaccination, there is a lack of research on how to optimally define the time between doses when two-dose vaccines are administrated to such groups. Under such conditions, modeling the real effect of each vaccine on the population is critical. Even though several efforts have been made to characterize vaccine effectiveness profiles, none of these initiatives enable characterization of the individual effect of each dose. Thus, this paper presents a novel methodology for estimating the vaccine effectiveness profile. It addresses the vaccine characterization problem by considering a deconvolution of relevant data profiles, treating them as an optimization process. The results of this approach enabled the independent estimation of the effectiveness profiles for the first and second vaccine doses and their use to find sweet spots for designing efficient vaccination strategies. Our methodology can enable a more effective and efficient contemporary response against the COVID-19 pandemic, as well as for any other disease in the future. Full article

We aimed to document vaccination coverage for five vaccines, predictors of each vaccine’s uptake and attitudes regarding adult vaccination. Adults visiting four pharmacies were randomly invited to participate during summer 2022. Among 395 participants (mean age 51.2 years, range 19–96), vaccination rates were 78.1% for influenza and 25.8% for herpes zoster (≥60 years old), 64.3% for pneumococcal disease (≥65 years old), 33.1% for tetanus, while 11.4% had received two and 74.8% ≥3 COVID-19 vaccine doses. Half of participants (50.1%) voiced some degree of hesitancy, and 1.3% were refusers. The strongest predictor of each vaccine’s uptake was doctor’s recommendation (OR range 11.33–37.66, p < 0.001) and pharmacist’s recommendation (4.01–19.52, p < 0.05), except for the COVID-19 vaccine, where the Attitude Towards Adult VACcination (ATAVAC) value of adult vaccination subscale’s score was the only predictor (OR: 5.75, p < 0.001). Regarding insufficient coverage, thematic content analysis revealed seven main themes. Insufficient knowledge, the absence of health professionals’ recommendation, perception of low susceptibility to disease, negligence and dispute of vaccine effectiveness were universal themes, whereas safety concerns and distrust in authorities were reported solely for COVID-19 vaccination. Designing public interventions aiming to increase trust in adult vaccination is essential in the aftermath of the COVID-19 pandemic. Health professionals’ role in recommending strongly adult vaccination is crucial. Full article