Serum IgG Antibodies Research Articles

Seroepidemiology of pertussis immunity in five provinces of China: A population-based, cross-sectional study

ABSTRACT This study aimed to evaluate the seroprevalence of Bordetella pertussis and persistence of antibodies following vaccination. We recruited 6060 healthy subjects from five provinces of China during 2017–2018. Serum IgG antibodies against pertussis toxin (anti-PT IgG) and filamentous hemagglutinin (anti-FHA IgG), and serum IgA antibodies against pertussis toxin (anti-PT IgA) were measured by ELISA. Geometric mean concentration (GMC), seropositivity rate, and recent infection rate were calculated. Among 0–6 years-olds, the anti-PT IgG, anti-PT IgA, and anti-FHA IgG GMCs were 6.4 IU/ml (95% CI 6.1–6.8), 2.8 IU/ml (95% CI 2.7–2.8), and 13.3 IU/ml (95% CI 12.4–14.2), respectively. The anti-PT IgG GMC increased in accordance with the primary vaccination series (4–6 months) and the toddler booster (18–24 months), but declined thereafter through to age 5 years [4.7 IU/ml (95% CI 4.2–5.4)]. The seropositivity rate of pertussis in >6 year-olds was 9.0% (95% CI 8.1–9.9) and the recent infection rate was 3.3% (95% CI, 2.7–3.8). Recent infection rate began to increase from 6 years of age, with peaks at 9, 20, 40, and ≥60 years of age. The anti-PT IgG GMCs of children aged 0–6 years who were vaccinated with DTaP, DTaP-IPV//PRP～T, and DTaP-Hib were 5.9 IU/ml (95% CI 5.6–6.3), 20.7 IU/ml (95% CI 15.6–27.8), and 11.7 IU/ml (95% CI 7.5–18.1) (p < .001), respectively (p < .001). Pertussis vaccination improves anti-PT IgG levels, however these wane soon after vaccination. Sero-estimated recent infection rates appear to increase from school age into adolescence and adulthood. Pertussis vaccine boosters should be considered in these age groups.

Anti-Porphyromonas gingivalis Antibody Levels in Patients With Stroke and Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Atrial fibrillation (AF) and stroke are two highly related conditions, with periodontitis and periodontal pathogens, such as Porphyromonas gingivalis (Pg), appearing to be the most prominent common risk factors. In this study, we evaluated studies assessing Pg infection via serum/plasma anti-Pg antibodies in patients with AF and/or stroke. Online databases (PubMed, Scopus, Embase, and the Web of Science) were screened for studies showing the association between anti-Pg antibodies with stroke and/or AF. Relevant data were extracted, and a subsequent random-effects meta-analysis was performed to calculate the pooled odds ratio (OR) or standardized mean difference (SMD) and 95% confidence intervals (CIs) for Pg seropositivity or anti-Pg antibody levels in stroke patients compared to controls. Sixteen studies were included in the systematic review. Based on the meta-analysis performed, there was no significant difference in Pg IgA and IgG levels between patients with stroke and controls (IgA: SMD 0.11, 95% CI -0.02 to 0.25, p = 0.1; IgG: SMD -0.12, 95% CI -1.24 to 0.99, p = 0.83). Similarly, no difference was observed between these groups in terms of Pg IgA and IgG seropositivity (IgA: OR 1.63, 95% CI 1.06-2.50, p = 0.026; IgG: OR 2.30, 95% CI 1.39-3.78, p < 0.001). Subsequently, we reviewed the results of six articles investigating serum or plasma IgG antibodies against Pg in patients with AF. Our results revealed a strict association between Pg infection and AF, with AF patients exhibiting either higher anti-Pg antibody levels or a higher prevalence of positive serum Pg antibodies. Our study supports the clinical utility of Pg infection assessment in patients with periodontitis and those with AF and solicits more focused studies to corroborate its use in clinical settings to enhance overall outcomes, reduce the risk of complications like stroke, and help fine-tune personalized therapies.

Epidemiological and clinical characteristics of dengue fever in Fuzhou, China, in 2023.

This study aimed to analyze the epidemiological and clinical characteristics of dengue fever (DF) in Fuzhou, the capital city of Fujian Province, southeast China. A retrospective analysis was performed on 251 cases of DF diagnosed at the fever clinic of the Second Affiliated Hospital of Fujian University of Chinese Medicine in Fuzhou City, Fujian Province. Epidemic characteristics, such as the number of cases, age distribution, sex distribution, seasonal distribution, and spatial distribution in each region, were analyzed. The patients' clinical manifestations, signs, auxiliary examinations, and prognoses were analyzed. The age distribution of DF cases was mainly concentrated in 30-39 years (20.72%) and 50-59 years (21.12%). There were no sex differences among the patients. Of these cases, 60.16% were concentrated on the lower floors, with retirees having the highest proportion. The seasonal peak of DF in Fuzhou area was from September to November. The SDE plot showed that the cases were mainly concentrated in Jin'an and Gulou districts. Etiological tests revealed serum NS1 antigen (97.61%), serum IgM antibody (15.14%), and serum IgG antibody (0.40%). There were no significant differences in clinical manifestations between the children's and non-children's groups. Laboratory tests have shown that the disease is prone to multi-system dysfunction, including the blood system, digestive system, urinary system and internal environment. ROC curve analysis showed that WBC, N, LY, PLT, and CRP levels had specific diagnostic values for DF. The epidemiological situation and clinical characteristics of DF in Fuzhou City were analyzed to guide the formulation of reasonable prevention and treatment measures.

Association between serum antibodies to oral microorganisms and nonalcoholic fatty liver disease in adults

BackgroundAlterations in the bacteria, such as the periodontal bacteria, might be considered potential risk factors for nonalcoholic fatty liver disease (NAFLD). Most studies analyzing this association have focused mainly on a specific periodontal bacteria (Porphyromonas gingivalis) and have involved relatively small study populations (tens or hundreds of individuals). To address this gap, a sizable, nationally representative adult population was utilized to investigate the association between the incidence of NAFLD and high serum IgG antibodies for 19 periodontal bacteria.MethodsTo explore this association, data from the Third National Health and Nutrition Examination Survey (NHANES III)—which provides a cross-sectional representation of the noninstitutionalized U.S. population, encompassing 33,994 individuals—were analyzed. Participants aged 40 years and above with data on NAFLD—determined by the gold standard of ultrasound examination (USON)—as well as comprehensive records of serum IgG antibodies against periodontal bacteria, were included, resulting in a final analysis subset of 6,330 individuals.ResultsUsing a cluster analysis based on the Socransky classification scheme for oral microorganisms, antibody titers for the 19 bacteria were grouped into four clusters—Red-Green, Orange-Blue, Yellow-Orange, and Orange-Red. When these clusters, as well as individual antibody relationships with NAFLD, were examined, the adjusted odds ratios (ORs) ranged from 0.958 [95% confidence interval (CI): 0.916, 1.003] to 1.021 [95% CI: 0.987, 1.055]. This indicated that no statistically significant associations were found (P > 0.05), underscoring the absence of a meaningful link.ConclusionsIn summary, it was discovered that there is currently no evidence to correlate serum antibodies to periodontal pathogens with NAFLD in the nationally representative NHANES III.Clinical trial numberNot applicable.

Serum IgG Antibody against Helicobacter pylori and the CagA-VacA s1 Genotype as a Predictor of Gastric Cancer Development: A Case-control Study

Helicobacter pylori (H. pylori)-induced inflammation increases the risk of developing various upper gastrointestinal conditions which may progress to gastric cancer (CA). Early prediction and detection of infection are crucial for reducing cancer-induced mortality rates. The present case-control study aimed to investigate the combination of serum and molecular markers and H. pylori-associated gastro-duodenal conditions as risk factors for predicting CA development in dyspeptic patients. Consecutive gastric biopsies and blood samples were collected from 100 adult dyspeptic patients. Serum IgG antibody levels against H. pylori were determined, and receiver operating characteristic (ROC) analysis was performed. The expression of the virulence genes cagA and vacA was evaluated by polymerase chain reaction (PCR). A significant association was reported between the disease condition and the status of several risk factors, such as family history, serum IgG antibody concentration, and the virulence genes cagA and vacA. Among the 71 H. pylori-positive patients, 35.2% (25/71) had CA. Both cagA and vacA genes were found in 46 out of 71 (64.7%) patients, and 92% (23/25) of CA patients carried the cagA+vacA s1 gene. ROC analysis of the serum IgG concentrations revealed AUC values of 0.81 and 0.78 for differentiating patients with non-ulcer dyspepsia from those with ulceration/inflammation and CA, respectively. The concordance between the IgG-positive and PCR-positive patients was 84% (k value=0.41). Patients who had a family history of CA with an increased serum IgG concentration and the presence of H. pylori cagA-vacA s1 genotypes may be considered strong predictors of future development of gastric pathologies, including CA.

Enhanced Broad-Spectrum Efficacy of an L2-Based mRNA Vaccine Targeting HPV Types 6, 11, 16, 18, with Cross-Protection Against Multiple Additional High-Risk Types

Background: Current L1-based human papillomavirus (HPV) vaccines provide type-specific protection but offer limited cross-protection against non-vaccine HPV types. Therefore, developing a broad-spectrum HPV vaccine is highly desirable. Methods: In this study, we optimized mRNA constructs and developed a multivalent L2-based mRNA vaccine encoding L2 aa 2-130, which includes all known neutralizing epitopes from four prevalent HPV types (HPV-6, -11, -16, and -18). We evaluated its immunogenicity in a mouse model and compared the efficacy of a commercially available mRNA delivery reagent with a custom-synthesized lipid nanoparticle (LNP) formulation. Results: We identified that a construct containing E01 (a 5′-untranslated region) and SL2.7 (a poly(A) polymerase recruitment sequence) significantly increased protein expression. The L2-based mRNA vaccine induced robust and long-lasting humoral immune responses, with significant titers of cross-reactive serum IgG antibodies against L2 epitopes. Notably, the vaccine elicited cross-neutralizing antibodies and conferred cross-protective immunity not only against vaccine-targeted HPV types but also against non-vaccine HPV types, following intravaginal challenge in mice. We also found that LNP delivered mRNA more effectively in vivo. Conclusions: The L2-based mRNA vaccine developed in this study shows significant potential for broad-spectrum protection against multiple HPV types. This approach offers a promising strategy for reducing the global burden of HPV-associated cancers.

CpG-adjuvanted virus-like particle vaccine induces protective immunity against Leishmania donovani infection.

Visceral leishmaniasis (VL) poses a significant public health challenge due to the lack of an approved human vaccine. We attempted to enhance the efficacy of virus-like particle vaccines expressing the Leishmania donovani promastigote surface antigen (LdPSA-VLP) by adjuvanting with CpG oligodeoxynucleotide (CpG-ODN). Here, adjuvanted vaccine-induced immune responses and their efficacies in mice challenged with mCherry-expressing L. donovani promastigotes were evaluated. Adjuvanted LdPSA-VLP vaccination significantly elevated parasite-specific IgG, IgG1, IgG2a, and IgG2b serum antibody levels. Additionally, vaccinated mice exhibited enhanced germinal center B cells and splenic T cell activities, compared to unimmunized mice. Importantly, adjuvanted LdPSA-VLPs reduced the levels of inflammatory cytokines IFN-γ and IL-6 in visceral organs, leading to decreased total parasite burden and protection against L. donovani challenge. Our findings indicate that CpG-ODN enhanced the protection conferred by LdPSA-VLPs, offering a promising step toward effective VL vaccine development.

Comparative Efficacy of Parenteral and Mucosal Recombinant Probiotic Vaccines Against SARS-CoV-2 and S. pneumoniae Infections in Animal Models.

The accumulation of specific IgG antibodies in blood serum is considered a key criterion for the effectiveness of vaccination. For several vaccine-preventable infections, quantitative indicators of the humoral response have been established, which, when reached, provide a high probability of protection against infection. The presence of such a formal correlate of vaccine effectiveness is crucial, for example, in organizing preventive measures and validating newly developed vaccines. However, can effective protection against infection occur when the level of serum antibodies is lower than that provided by parenteral vaccination? Will protection be sufficient if the same vaccine antigen is administered via mucosal membranes without achieving high levels of specific IgG circulating in the blood? In this study, we compared the immunogenicity and protective efficacy of parenteral and mucosal forms of vaccines in experimental animals, targeting infections caused by the SARS-CoV-2 coronavirus and Streptococcus pneumoniae. We investigated the protective properties of a fragment of the coronavirus S1 protein administered intramuscularly with an adjuvant and orally as part of the probiotic strain Enterococcus faecium L3 in a Syrian hamster model. A comparative assessment of the immunogenicity and protective efficacy of a recombinant tandem (PSP) of immunogenic peptides from S. pneumoniae surface proteins, administered either parenterally or orally, was performed in a Balb/c mouse model. Both models demonstrated significant differences in the immunogenicity of parenteral and oral vaccine antigens, but comparable protective efficacy.

Strain- and Subtype-Specific Replication of Genotype 3 Hepatitis E Viruses in Mongolian Gerbils

Since Mongolian gerbils are broadly susceptible to hepatitis E virus (HEV), including genotypes 1, 4, 5, and 8 (HEV-1, HEV-5, HEV-5, and HEV-8) and rat HEV, they are a useful small animal model for HEV. However, we have observed that the subtypes HEV-3k and HEV-3ra in genotype 3 HEV (HEV-3) were not infected efficiently in the gerbils. A small-animal model for HEV-3 is also needed since HEV-3 is responsible for major zoonotic HEV infections. To investigate whether gerbils can be used as animal models for other subtypes of HEV-3, we injected gerbils with five HEV-3 subtypes (HEV-3b, -3e, -3f, -3k, and -3ra) and compared the infectivity of the subtypes. We detected viral RNA in the gerbils’ feces. High titers of anti-HEV IgG antibodies in serum were induced in all HEV-3b/ch-, HEV-3f-, and HEV-3e-injected gerbils. Especially, the HEV-3e-injected animals released high levels of viruses into their feces for an extended period. The virus replication was limited in the HEV-3b/wb-injected and HEV-3k-injected groups. Although viral RNA was detected in HEV-3ra-injected gerbils, the copy numbers in fecal specimens were low; no antibodies were detected in the sera. These results indicate that although HEV-3′s infectivity in gerbils depends on the subtype and strain, Mongolian gerbils have potential as a small-animal model for HEV-3. A further comparison of HEV-3e with different genotype strains (HEV-4i and HEV-5) and different genera (rat HEV) revealed different ALT elevations among the strains, and liver damage occurred in HEV-4i- and HEV-5-infected but not HEV-3e- or rat HEV-infected gerbils, demonstrating variable pathogenicity across HEVs from different genera and genotypes in Mongolian gerbils. HEV-4i- and HEV-5-infected Mongolian gerbils might be candidate animal models to examine HEV’s pathogenicity.

Factors Associated with IgG/IgM Levels after SARS-CoV-2 Vaccination in Patients with Head and Neck Cancer.

This study evaluated the factors influencing IgG/IgM antibody levels in 120 patients with head and neck cancer (HNC) following vaccination with inactivated SARS-CoV-2 vaccines. Each patient's demographic and clinical data were documented, and serum IgG and IgM antibodies were detected using a commercial magnetic chemiluminescence enzyme immunoassay kit. The results indicated that while all patients had received at least one vaccine dose, 95 tested positive for IgG and 25 were negative. A higher proportion of IgG-positive patients had received three vaccine doses. Comparatively, gamma-glutamyl transferase levels were elevated in IgM-negative patients. The study further differentiated patients based on their treatment status: 46 were treatment-naive and 74 had received chemotherapy combined with immune checkpoint inhibitors (ICT) at enrollment. Despite similar baseline characteristics and time from vaccination to antibody detection, IgM positivity was significantly lower in the ICT group, with no significant difference in IgG positivity between the treatment-naive and ICT groups. A multivariable analysis identified the number of vaccine doses as an independent factor of IgG positivity, while ICT emerged as an independent risk factor for IgM positivity. Additionally, IgG titers generally declined over time, although patients with higher baseline IgG levels maintained higher titers longer. In conclusion, ICT in patients with HNC does not significantly affect IgG levels post-vaccination. However, booster vaccinations have been shown to be associated with higher IgG positivity, although these levels gradually decrease over time.

Toxoplasma Gondii infection and cardiovascular mortality: sex-specific differences in a United States population-based cohort study

BackgroundAlthough Toxoplasma gondii (T. gondii) infection has been linked to cardiac injury, the extent to which it increases the risk of cardiovascular disease (CVD) mortality remains unclear. We aimed to assess the association between T. gondii infection and CVD mortality in the United States population.MethodsThis study used data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2009 and 2014 to investigate the association between T. gondii infection and CVD mortality. The T. gondii infection status was determined by measuring serum T. gondii IgG antibody levels. CVD mortality outcomes were ascertained through linkage with the national mortality index records. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) of T. gondii infection on CVD mortality.ResultsA total of 10,237 (Male, n = 5010; Female, n = 5227) individuals aged ≥ 20 years were included in the analysis, of which 1,632 were positive for T. gondii serum IgG antibodies. After a median follow-up of eight years, there were 312 deaths due to CVD. In multivariable-adjusted analyses, the risk of death from CVD was 40% higher in T. gondii-seropositive men compared with seronegative men (HR: 1.40; 95%CI: 1.02–1.93), but not in women (HR: 0.87; 95% CI: 0.57–1.34). These results remained consistent in further stratified and sensitivity analyses.ConclusionIn this large population-based cohort study, T. gondii infection was associated with an increased risk of CVD mortality in men, but not in women. Further studies are required to elucidate the underlying mechanisms and potential sex-specific differences in the effects of T. gondii infection on CVD mortality. Future investigations should focus on validating these results and exploring the potential implications for cardiovascular risk assessment and management.

Examination of diet quality and alcohol on serum IgG levels after first and second COVID-19 vaccines.

The change of IgG of COVID-19 vaccine was thought to be an effect of diet quality or daily habits. This study aimed to correlate diet quality and healthy living factors with serum IgG response in the blood. Participants were selected from volunteers who had their first vaccination and did not have COVID-19 disease (Male = 21 Female = 40). Serum IgG levels were measured on average (avg) 28 days after the COVID-19 vaccine. Information was obtained directly from the participants by questionnaire method (Food consumption record, frequency of food consumption, Diet Quality Index [(DQI], etc.). A significant difference was observed in the IgG levels of the second measurement of age (young/middle) and gender (male/female) (p < 0.05). A significant difference was found in the first measurement of serum IgG levels and IgG avgs of those with medium diet quality and those who did not drink alcohol (p < 0.05). When the IgG2/1 ratio was examined between alcohol users and nonalcohol, a significant increase was observed about two times in non-alcohol users (p = 0.039). There is a positive significant moderate strength relationship between the second measurements of IgG and anthropometric measurements and the first, second, and avg measurements of IgG with DQI. It was found that there was a negative significant medium-strength relationship between individuals' amount of alcohol consumption and IgG avg (r = -0.535, p = 0.009). Medium diet quality has been seen to affect antibody levels positively. At the same time, it is thought that alcohol use negatively affects serum IgG antibody response in the long term. Other than that, there was shown to be a correlation between IgG levels and DQI.

Rotavirus-Specific Maternal Serum Antibodies and Vaccine Responses to RV3-BB Rotavirus Vaccine Administered in a Neonatal or Infant Schedule in Malawi.

High titres of rotavirus-specific maternal antibodies may contribute to lower rotavirus vaccine efficacy in low- and middle-income countries (LMICs). RV3-BB vaccine (G3P[6]) is based on a neonatal rotavirus strain that replicates well in the newborn gut in the presence of breast milk. This study investigated the association between maternal serum antibodies and vaccine response in infants administered the RV3-BB vaccine. Serum was collected antenatally from mothers of 561 infants enrolled in the RV3-BB Phase II study conducted in Blantyre, Malawi, and analysed for rotavirus-specific serum IgA and IgG antibodies using enzyme-linked immunosorbent assay. Infant vaccine take was defined as cumulative IgA seroconversion (≥3 fold increase) and/or stool vaccine shedding. Maternal IgA or IgG antibody titres did not have a negative impact on vaccine-like stool shedding at any timepoint. Maternal IgG (but not IgA) titres were associated with reduced take post dose 1 (p < 0.005) and 3 (p < 0.05) in the neonatal vaccine schedule group but not at study completion (week 18). In LMICs where high maternal antibodies are associated with low rotavirus vaccine efficacy, RV3-BB in a neonatal or infant vaccine schedule has the potential to provide protection against severe rotavirus disease.

Ipsilateral or contralateral boosting of mice with mRNA vaccines confers equivalent immunity and protection against a SARS-CoV-2 Omicron strain.

Boosting with mRNA vaccines encoding variant-matched spike proteins has been implemented to mitigate their reduced efficacy against emerging SARS-CoV-2 variants. Nonetheless, in humans, it remains unclear whether boosting in the ipsilateral or contralateral arm with respect to the priming doses impacts immunity and protection. Here, we boosted K18-hACE2 mice with either monovalent mRNA-1273 (Wuhan-1 spike) or bivalent mRNA-1273.214 (Wuhan-1 + BA.1 spike) vaccine in the ipsilateral or contralateral leg after a two-dose priming series with mRNA-1273. Boosting in the ipsilateral or contralateral leg elicited equivalent levels of serum IgG and neutralizing antibody responses against Wuhan-1 and BA.1. While contralateral boosting with mRNA vaccines resulted in the expansion of spike-specific B and T cells beyond the ipsilateral draining lymph node (DLN) to the contralateral DLN, administration of a third mRNA vaccine dose at either site resulted in similar levels of antigen-specific germinal center B cells, plasmablasts/plasma cells, T follicular helper cells, and CD8+ T cells in the DLNs and the spleen. Furthermore, ipsilateral and contralateral boosting with mRNA-1273 or mRNA-1273.214 vaccines conferred similar homologous or heterologous immune protection against SARS-CoV-2 BA.1 virus challenge with equivalent reductions in viral RNA and infectious virus in the nasal turbinates and lungs. Collectively, our data show limited differences in B and T cell immune responses after ipsilateral and contralateral site boosting by mRNA vaccines that do not substantively impact protection against an Omicron strain.IMPORTANCESequential boosting with mRNA vaccines has been an effective strategy to overcome waning immunity and neutralization escape by emerging SARS-CoV-2 variants. However, it remains unclear how the site of boosting relative to the primary vaccination series shapes optimal immune responses or breadth of protection against variants. In K18-hACE2 transgenic mice, we observed that intramuscular boosting with historical monovalent or variant-matched bivalent vaccines in the ipsilateral or contralateral limb elicited comparable levels of serum spike-specific antibody and antigen-specific B and T cell responses. Moreover, boosting on either side conferred equivalent protection against a SARS-CoV-2 Omicron challenge strain. Our data in mice suggest that the site of intramuscular boosting with an mRNA vaccine does not substantially impact immunity or protection against SARS-CoV-2 infection.

Bovine Respiratory Syncytial Virus Nanovaccine Induces Long-Lasting Humoral Immunity in Mice.

With limited therapies and vaccines available, human respiratory syncytial virus (HRSV) has a significant negative health impact on all age groups but particularly on infants, young children, and older adults. Bovine respiratory syncytial virus (BRSV) is pathogenically and antigenically similar to HRSV. Building upon previous studies using a BRSV nanovaccine coencapsulating multiple proteins, this work demonstrates the development and comparative evaluation of a coencapsulated nanovaccine to a cocktail nanovaccine formulation composed of polyanhydride nanoparticles encapsulating BRSV postfusion (F) glycoprotein and CpG ODN 1668 coadjuvant delivered simultaneously with nanoparticles encapsulating BRSV attachment glycoprotein (G) and CpG ODN 1668. These nanovaccine formulations were administered to C57BL/6 mice by one of two prime-boost regimens (i.e., intranasal/intranasal or intranasal/subcutaneous) followed by assessment of humoral immunity. The cocktail nanovaccine induced sustained anti-F and anti-G serum IgG antibody responses for 12 weeks postprimary immunization. Using polyanhydride particles to deliver G protein in a prime-boost regime also significantly induced serum anti-G antibodies compared to protein and coadjuvant alone. Serum IgG induced by the nanovaccine demonstrated virus-neutralizing capability from 42 to 119 days postprimary immunization. Further, anti-F IgG antibodies were detected in the bronchoalveolar lavage fluid of vaccinated animals. Finally, the nanovaccine induced long-lived anti-F antibody secreting plasma cells that were detectable in the bone marrow 205 days postprimary immunization. Overall, the BRSV nanovaccine(s) successfully induced long-lived humoral immune responses capable of virus neutralization, making this a promising vaccine candidate for further evaluation in other relevant animal models.

Influenza A Vaccine Candidates Based on Virus-like Particles Formed by Coat Proteins of Single-Stranded RNA Phages Beihai32 and PQ465.

Efficient control of influenza A infection can potentially be achieved through the development of broad-spectrum recombinant vaccines based on conserved antigens. The extracellular domain of the transmembrane protein M2 of influenza A virus (M2e) is highly conserved but poorly immunogenic and needs to be fused to an adjuvant protein or carrier virus-like particles (VLPs) to increase immunogenicity and provide protection against infection. In this study, we obtained VLPs based on capsid proteins (CPs) of single-stranded RNA phages Beihai32 and PQ465 bearing the M2e peptides. Four copies of the M2e peptide were linked to the C-terminus of the CP of phage Beihai32 and to the N and C termini of the CP of phage PQ465. The hybrid proteins, being expressed in Escherichia coli, formed spherical VLPs of about 30 nm in size. Immunogold transmission electron microscopy showed that VLPs formed by the phage PQ465 CP with a C-terminal M2e fusion present the M2e peptide on the surface. Subcutaneous immunization of mice with VLPs formed by both CPs containing four copies of the M2e peptide at the C termini induced high levels of M2e-specific IgG antibodies in serum and provided mice with protection against lethal influenza A virus challenge. In the case of an N-terminal fusion of M2e with the phage PQ465 CP, the immune response against M2e was significantly lower. CPs of phages Beihai32 and PQ465, containing four copies of the M2e peptide at their C termini, can be used to develop recombinant influenza A vaccine.

Comprehensive Microbiological and Metagenomic Analysis of the Guillain–Barré Syndrome Outbreak in Lima, 2019

In 2018/2019, two large Guillain–Barré Syndrome (GBS) outbreaks took place in Peru. Here, we report a comprehensive analysis of biological samples from GBS patients from the 2019 outbreak. We applied metagenomic, microbiologic, and serological analyses to different biological samples collected from GBS patients. Further phenotypic and genomic characterization was conducted on Campylobacter jejuni isolates from GBS samples. Microbiologic and metagenomic analyses revealed several patients with multiple co-infections, yet no common infectious agents were found other than C. jejuni. Four C. jejuni isolates were isolated from rectal swabs. Twenty-one patients had detectable IgG serum antibodies related to C. jejuni, of whom seven had IgM antibodies. Genomic analyses showed that these four strains were clonal (ST2993) and contained the class A lipooligosaccharide biosynthesis locus. These results further support the idea that that C. jejuni is the etiological agent that triggered the GBS outbreak in Peru in 2019 and that the strains are not restricted to Peru, hence could be regarded as a broad public health concern. Furthermore, though we cannot delineate the role played by co-infections in GBS development, results obtained herein highlight metagenomic analysis as a potential new tool for depicting a yet unknown area of research in GBS.

Humoral immune response as an indicator for protection against Covid-19 after anti-SARS-COV2-booster vaccination in hematological and oncological patients.

Cancer patients are at a higher risk to develop severe COVID-19 symptoms after SARS-CoV-2 infection compared to the general population and regularly show an impaired immune response to SARS-CoV-2 vaccination. In our oncological center, 357 patients with hematological and oncological diseases were monitored for neutralizing antibodies from October 2021 over 12 months. All patients had received three anti-SARS-CoV-2 vaccinations with an mRNA-(Comirnaty/BionTech or Spikevax/Moderna) or a vector vaccine (Vakzevria/AstraZeneca or JCOVDEN/Johnson&Johnson). Neutralizing anti-SARS-CoV-2 IgG antibodies in the patients' sera were detected within 3 months before, 3-10 weeks and 5-7 months after the booster vaccination (third vaccination). 112 patients developed a breakthrough SARS-CoV-2 infection during the observation period. High anti-SARS-Cov-2 antibody levels before infection significantly protected against symptomatic Covid-19 disease (p = .003). The median antibody titer in patients with asymptomatic Covid-19 disease was 2080 BAU/ml (binding antibody units per Milliliter) and 765 BAU/ml in symptomatic patients. 98% of the solid tumor patients reached seroconversion after the booster vaccination in comparison to 79% of the hematological patients. High antibody titers of >2080 BAU/ml after the booster vaccination were detected in 61% of the oncological and 34.8% of the hematological patients. 7-10 months after the booster vaccination, the anti-SARS-CoV-2 antibody titer declined to an average of 849 BAU/ml. Considering the heterogenous humoral immune response of cancer patients observed in this study, an individual vaccination strategy based on regular measurement of anti-SARS-CoV-2 antibody levels should be considered in contrast to fixed vaccination intervals.

Application of PLGA-PEG-PLGA Nanoparticles to Percutaneous Immunotherapy for Food Allergy.

Compared with oral or injection administration, percutaneous immunotherapy presents a promising treatment modality for food allergies, providing low invasiveness and safety. This study investigated the efficacy of percutaneous immunotherapy using hen egg lysozyme (HEL)-loaded PLGA-PEG-PLGA nanoparticles (NPs), as an antigen model protein derived from egg white, compared with that of HEL-loaded chitosan hydroxypropyltrimonium chloride (CS)-modified PLGA NPs used in previous research. The intradermal retention of HEL in excised mouse skin was measured using Franz cells, which revealed a 2.1-fold higher retention with PLGA-PEG-PLGA NPs than that with CS-modified PLGA NPs. Observation of skin penetration pathways using fluorescein-4-isothiocyanate (FITC)-labeled HEL demonstrated successful delivery of HEL deep into the hair follicles with PLGA-PEG-PLGA NPs. These findings suggest that after NPs delivery into the skin, PEG prevents protein adhesion and NPs aggregation, facilitating stable delivery deep into the skin. Subsequently, in vivo percutaneous administration experiments in mice, with concurrent iontophoresis, demonstrated a significant increase in serum IgG1 antibody production with PLGA-PEG-PLGA NPs compared with that with CS-PLGA NPs after eight weeks of administration. Furthermore, serum IgE production in each NP administration group significantly decreased compared with that by subcutaneous administration of HEL solution. These results suggest that the combination of PLGA-PEG-PLGA NPs and iontophoresis is an effective percutaneous immunotherapy for food allergies.

Shedding reduction and immunity modulation in piglets with an inactivated Mycoplasma hyopneumoniae vaccine encapsulated in nanostructured SBA-15 silica

Mycoplasma (M.) hyopneumoniae is a primary etiological agent of porcine enzootic pneumonia (PEP), a disease that causes significant economic losses to pig farming worldwide. Current commercial M. hyopneumoniae vaccines induce partial protection, decline in preventing transmission of this pathogen or inducing complete immunity, evidencing the need for improving vaccines against PEP. In our study, we aimed to test the effectiveness of the SBA-15 ordered mesoporous silica nanostructured particles as an immune adjuvant of a vaccine composed of M. hyopneumoniae strain 232 proteins encapsulated in SBA-15 and administered by intramuscular route in piglets to evaluate the immune responses and immune-protection against challenge. Forty-eight 24-day-old M. hyopneumoniae-free piglets were divided into four experimental groups with different protocols, encompassing a commercial vaccine against M. hyopneumoniae, SBA-15 vaccine, SBA-15 adjuvant without antigens and a non-immunized group. All piglets were challenged with the virulent strain 232 of M. hyopneumoniae. Piglets that received the SBA-15 and commercial vaccine presented marked immune responses characterized by anti-M. hyopneumoniae IgA and IgG antibodies in serum, anti-M. hyopneumoniae IgA antibodies in nasal mucosa and showed an upregulation of IL-17 and IL-4 cytokines and downregulation of IFN-γ in lungs 35 days post-infection. Piglets immunized with SBA-15 vaccine presented a reduction of bacterial shedding compared to piglets immunized with a commercial bacterin. In addition, piglets from SBA-15 adjuvant suspension group presented increased IL-17 gene expression in the lungs without involvement of Th1 and Th2 responses after challenge. These results indicated that SBA-15 vaccine induced both humoral and cell-mediated responses in the upper respiratory tract and lungs, first site of replication and provided protection against M. hyopneumoniae infection with a homologous strain with reduction of lung lesions and bacterial shedding. Finally, these results enhance the potential use of new technologies such as nanostructured particles applied in vaccines for the pig farming industry.