Envelope Antigen Research Articles

The impact of hepatitis B surface antigen seroconversion on the durability of functional cure induced by pegylated interferon alpha treatment

BackgroundHepatitis B surface antigen (HBsAg) loss is regarded as a pivotal criterion for assessing functional cure in patients diagnosed chronic hepatitis B (CHB). We conducted the research to investigate the real-world performance of HBsAg seroconversion in sustaining HBsAg loss.MethodsThis retrospective analysis confirmed 295 patients who attained HBsAg loss through combination therapy involving nucleos(t)ide analogues (NAs) and pegylated interferon alpha (peg-IFNα). Employing Kaplan–Meier estimates method to conduct survival analysis. The forest plot was used to visualize the results of multivariate Cox regression, and selected variables were included in the nomogram.ResultsHBsAg seroreversion was observed in 45 patients during follow-up periods, with a lower recurrence risk in patients with HBsAg seroconversion at the end of peg-IFNα therapy (EOT) (10.3% vs 37.3% at 96-week, P < 0.0001). Moreover, the sustainability of hepatitis B surface antibody (anti-HBs) in participants continuing therapy after HBsAg seroconversion was superior to those discontinued prematurely (72.5% vs 54.5% at 96 weeks, P = 0.012). Additionally, the former group was also relatively less likely to experience HBsAg reversion during long-term observation (8.4% vs 14.3% at 96 weeks, P = 0.280). Hepatitis B envelope antigen (HBeAg) status, anti-HBs status and consolidation treatment screened by multivariable analysis were utilized to construct a predictive model for HBsAg reversion. The concordance index(C-index = 0.77) and calibration plots indicated satisfactory discrimination and consistency of nomogram.ConclusionsHBsAg seroconversion was beneficial for sustaining functional cure in patients treated with peg-IFNα. Continuing consolidation therapy after HBsAg seroconversion also contributed to maintain HBsAg seroconversion and improve the durability of HBsAg loss. The nomogram illustrated its efficacy as a valuable instrument in showcasing survival probability of functional cure.

Signal peptide exchange alters HIV-1 envelope antigenicity and immunogenicity.

HIV-1 envelope (Env) is the key target for antibodies (Abs) against the virus and thus an important HIV-1 vaccine component. Env is synthesized from a gp160 precursor with a signal peptide (SP) at its N-terminus. This study investigated the influence of the SP on Env antigenicity and immunogenicity. Env proteins from two HIV-1 isolates, AA05 and AC02, were analyzed as gp120 and gp160 in their native wild-type (WT) forms and as chimeras with swapped SPs (AA05-02 and AC02-05). The WT and chimeric Env were assessed for antigenicity and glycosylation using monoclonal antibodies (mAbs) and glycan probes. Immunogenicity was tested in mice using three vaccine types: gp120 protein, gp120 DNA+gp120 protein, and gp120 DNA+gp160 DNA. The recombinant AC02 gp120 protein was antigenically superior to AA05 as indicated by higher reactivity with most mAbs tested. When SPs were swapped, the antigenicity of the chimeric gp120s (AA05-02 and AC02-05) resembled that of the gp120s from which the SPs were derived; AA05-02 was similar to AC02 and vice versa. Glycan probe reactivity followed a similar pattern: AA05-02 and AC02 showed similar affinity to high-mannose specific mAbs and lectins. Interestingly, the antigenicity of gp160s showed an opposite pattern; membrane-bound gp160 expressed with the AA05 SP (AA05 and AC02-05) showed greater mAb binding than gp160 with the AC02 SP (AC02 and AA05-02). Mice immunized with gp120 protein showed that AA05-02 induced stronger cross-reactive binding Ab responses than AA05 WT, and AC02 elicited stronger responses than AC02-05, indicating AC02 SP enhanced gp120 immunogenicity. However, when DNA vaccines were included (gp120 DNA+gp120 protein and gp120 DNA+gp160 DNA), the use of heterologous SPs diminished the immunogenicity of the WT immunogens. Among the three vaccine regimens tested, only gp120 DNA+gp160 DNA immunization elicited low-level Tier 2 neutralizing Abs, with AA05 WT inducing Abs with greater neutralization capabilities than AA05-02. These data demonstrate that the SP can significantly impact the antigenicity and immunogenicity of HIV-1 Env proteins. Hence, while SP swapping is a common practice in constructing Env immunogens, this study highlights the importance of careful consideration of the effects of replacing native SPs on the immunogenicity of Env vaccines.

Efficacy and safety of therapeutic vaccines for the treatment of chronic hepatitis B: A systematic review and meta-analysis of randomized controlled trials update.

Most people diagnosed with chronic hepatitis B (CHB) need treatment to help reduce the risk of liver disease and limit disease transmission. Therapeutic vaccine (TV) candidates have been under study for their clinical effects on inducing HBV-specific host immune responses. This review aimed to systematically synthesize updated evidence on the efficacy and safety of TVs in patients with CHB. This systematic review was performed by searching different databases from January to February 2021. Completed randomized controlled trials that reported TVs' efficacy and/or safety for treating CHB compared with the standard of care (SOC) or placebo were included. Efficacy and safety estimates were reported as the logarithm of the odds ratio and risk differences, respectively. I2 > 50% was considered significant heterogeneity. Significant publication bias was considered when Egger's test P value < .10. The risk of bias was assessed using the Cochrane Risk of Bias tool. The GRADE methodology was used to assess the certainty of the evidence for each outcome. Twenty-four articles with 2889 pooled samples were included. TVs made a significant difference in hepatitis B envelope antigen (HBeAg) SC (log OR = 0.76, P = .01) and (log OR = 0.40, P = .03) compared to placebo and combination therapy, respectively. HBeAg SC was significantly affected by TVs at the end of follow up (log OR = 0.49, P = .01), with significant HBsAg mean difference (MD = -0.62, P = .00). At the end of treatment, the TVs had no significant effect on HBV DNA negativity over the SOC (log OR = 0.62, P = .09) or placebo (log OR = -0.07, P = .91). TVs do not significantly affect the risk of serious adverse events (RD 0.02, 95% CI 0.00-0.04). In patients with CHB, TVs had significant effects on HBeAg SC compared to the SOC or placebo. There was no significant difference between serious adverse events. TVs are promising treatment strategy to overcome CHB.

Paternal Preconception Hepatitis B Virus Infection and Risk of Congenital Heart Disease in Offspring

Previous evidence suggests that maternal hepatitis B virus (HBV) infection during prepregnancy or pregnancy is associated with congenital heart diseases (CHDs) in offspring. However, the association of paternal HBV infection with CHDs is not well examined. To explore the association of paternal preconception HBV infection with CHDs in offspring. This retrospective cohort study used propensity score matching of data from the Chinese National Free Preconception Checkup Project (NFPCP) from January 1, 2010, to December 31, 2018. Male participants whose wives were aged 20 to 49 years, were uninfected with HBV, and successfully conceived within 1 year after prepregnancy examination were enrolled. Data were analyzed from March 2023 to February 2024. The primary exposure was paternal preconception HBV infection status, including uninfected, previous infection (both serum hepatitis B surface antigen and hepatitis B envelope antigen negative), and new infection (serum hepatitis B surface antigen positive). Maternal HBV immune status was further classified as immune or susceptible. The main outcome was CHDs, which were collected from the birth defect registration card of the NFPCP. Logistic regression with robust error variances was used to estimate the association between paternal preconception HBV infection and CHDs in offspring. A total of 6 675 540 couples participated in the NFPCP service. After matching husbands with and without preconception HBV infection in a 1:4 ratio, 3 047 924 couples (median age of husbands, 27 years [IQR, 25-30 years]) were included in this study. Of these couples, 0.025% had offspring with CHDs. Previous paternal HBV infection was independently associated with CHDs in offspring (adjusted relative risk [ARR], 1.40; 95% CI, 1.11-1.76) compared with no infection. Similar results were obtained in subgroup analyses according to maternal HBV immune status. Compared with couples with uninfected husbands and susceptible wives, the risk of CHDs in offspring among couples with previously HBV-infected husbands was similar in couples with wives with susceptible immune status (ARR, 1.49; 95% CI, 1.10-2.03) and in those with wives with immunity (ARR, 1.49; 95%CI, 1.07-2.09). A significantly higher CHD risk in offspring was found among couples with newly infected husbands and immune wives (ARR, 1.38; 95% CI, 1.05-1.82), but there was no difference in risk among those with newly infected husbands and susceptible wives (ARR, 0.99; 95% CI, 0.72-1.36). No interactions were found between maternal immune status and paternal HBV infection. In this cohort study using propensity score matching, previous paternal preconception HBV infection was associated with CHD risk in offspring. The findings suggest that personalized reproductive guidance regarding HBV screening and staying free of HBV infection should be provided for both wives and husbands.

Chronic hepatitis B virus infection in Eastern Ethiopia: Clinical characteristics and determinants of cirrhosis.

Chronic hepatitis B (CHB) virus infection is a major cause of liver-associated morbidity and mortality, particularly in low-income countries. A better understanding of the epidemiological, clinical, and virological characteristics of CHB will guide appropriate treatment strategies and improve the control and management of CHB in Ethiopia. To investigate the characteristics of CHB in Eastern Ethiopia and assess the efficacy and safety of antiviral treatment. This cohort study included 193 adults who were human immunodeficiency virus-negative with CHB between June 2016 and December 2019. Baseline assessments included chemistry, serologic, and viral markers. χ 2 tests, Mann-Whitney U tests, and logistic regression analyses were used to identify the determinants of cirrhosis. Tenofovir disoproxil fumarate (TDF) was initiated using treatment criteria from the Ethiopian CHB pilot program. A total of 132 patients (68.4%) were men, with a median age of 30 years [interquartile range (IQR): 24-38]. At enrollment, 60 (31.1%) patients had cirrhosis, of whom 35 (58.3%) had decompensated cirrhosis. Khat use, hepatitis B envelope antigen positivity, and a high viral load were independently associated with cirrhosis. Additionally, 66 patients (33.4%) fulfilled the treatment criteria and 59 (30.6%) started TDF. Among 29 patients who completed 24 months of treatment, the median aspartate aminotransferase to platelet ratio index declined from 1.54 (IQR: 0.66-2.91) to 1.10 (IQR: 0.75-2.53) (P = 0.002), and viral suppression was achieved in 80.9% and 100% of patients after 12 months and 24 months of treatment, respectively. Among the treated patients, 12 (20.3%) died within the first 6 months of treatment, of whom 8 had decompensated cirrhosis. This study highlights the high prevalence of cirrhosis, initial mortality, and the efficacy of TDF treatment. Scaling up measures to prevent and control CHB infections in Ethiopia is crucial.

Prevalence of HBV genotypes among patients attending Moi Teaching and Referral Hospital liver clinic.

Hepatitis B virus (HBV) belongs to the genus Orthohepadnavirus, of Hepadnaviridae family, smallest human deoxyribonucleic acid (DNA) virus with 3200 bp in a partially double-stranded circular DNA. Globally, about 2 billion people are infected with over 65 million of the chronically infected residing in Africa. Ten HBV genotypes (A-J) have been reported across the globe. Based on the World Health Organization (WHO) African Regions including Kenya have high HBV prevalence rates yet the data on prevalence rates of the various HBV genotypes and their associated biomarkers is very scanty. A cross-sectional descriptive study with purposive sampling was conducted in which a census of patients with chronic Hepatitis B (CHB) with history >6-month were reviewed for eligibility. Demographics data was abstracted from patient files and blood samples drawn for genotyping, viral load using Rotor gene Q Polymerase Chain Reaction (PCR) equipment, Hepatitis B surface Antigen (HBsAg), Hepatitis B envelope antigen (HbeAg) and Hepatitis B core antibody (Anti-HBc) using Cobas e411 machine. Out of a total of 83 patients, 43 (52%) were eligible; males 29 (67.4%), females 14 (32.6%) with mean ages of 35.1±10.8 and 34.3±9.3 respectively. Genotypes A were 34(79.1%), B were 5(11.6%), C-D were 0 while E-J were 9(20.9%). All cases of genotype B were associated with co-infection of genotype A. Majority were HBeAg negative with HBV DNA >10 IU/ml (81.4% and 86.0% respectively) with distribution among all the genotypes. Across genotypes, viral load mean percentage comparisons were: A vs. A/B = 2600 (p = 0.09), A vs. E-J = 5260 (p = 0.09) and A/B vs. E-J = 200 (p = 0.28). The most prevalent genotype was A followed by mixed co-infection of genotype A/B. Genotype A was associated with HBV DNA viral loads > 10IU/ml and high rates of HBeAg negativity. Genotypes E-J were also detected though not characterized.

Variations in Plasma Glucose, Testosterone, and Tumor Necrosis Factor-alpha in Relationship with Polycystic Ovary Syndrome and Viral Seromarkers in Infertile Women: A Case–Control Observational Study

Study Background: Polycystic ovary syndrome (PCOS) is a common cause of infertility in Nigeria which is associated with insulin resistance. Insulin resistance may be induced by elevated inflammatory cytokines, androgen excess (testosterone), and irregular menstruation or anovulation. Aim and Objective: This work was designed to determine possible variations in plasma glucose, testosterone, and tumor necrosis factor-alpha (TNFα) in relationship with PCOS and viral seromarkers in infertile women. Materials and Methods: Two hundred and fourteen (214) primary infertility women with PCOS aged 37 ± 4.93 years diagnosed through ultrasound were recruited as test subjects while one hundred (100) age-matched primary infertility women without PCOS were recruited as control. All subjects were negative to Giemsa thick blood film staining for the detection of Plasmodium and Ziehl–Neelsen staining for the detection of acid–fast bacilli. HIVp24 antigen and antibody, plasma testosterone, antibody to hepatitis C virus (anti-HCV), and envelope antigen to hepatitis B Virus (HBeAg) were determined in the subjects by enzyme-linked immunosorbent assay while blood glucose was measured spectrophotometrically. Results: The results obtained showed a higher frequency of 0.93% (2) HIVP24antigen-antibody, 6.5% (17) anti-HCV, 14.5% (31) HBeAg, and 0.5% (1) HIVP24 + HBeAg (except for HIVP24 antigen and antibody) in PCOS women than the frequency of viral seromarkers of 1% (1) HIVP24 antigen and antibody, 6% (6) anti-HCV, 8% (8) HBeAg, and 0% (0) HIVP24 + HBeAg in non-PCOS control women. There was a significant association between PCOS and expression of viral seromarkers; there was a significantly higher fasting plasma glucose and testosterone level in all PCOS women with or without viral seromarkers (P &lt; 0.05). There was a significantly higher plasma TNFα in PCOS women that expressed viral seromarkers than in PCOS women who do not express any of the viral seromarkers (P &lt; 0.05). There was a significantly higher plasma TNFα in PCOS and non-PCOS women although more in PCOS women that expressed viral seromarkers than in women without any viral seromarker (P &lt; 0.05). Conclusion: PCOS may be characterized by elevated plasma fasting glucose, testosterone, and expression of viral seromarkers while viral infection could also trigger higher plasma TNFα in PCOS women than in non-PCOS women infected with viral agent.

Molecular Characterization of Hepatitis B Virus among HIV Positive and HIV Negative Pregnant Antenatal Women in Federal Capital Territory Abuja Hospital

A significant contributor to chronic hepatitis, cirrhosis and hepatocellular carcinoma is the Hepatitis B Virus (HBV). Hepatitis B Virus (HBV) is a major cause of Chronic Hepatitis, cirrhosis and Hepatocellular Cancer (HCC). The incidence of HBV-related HCC cases is projected to increase for at least two decades due to the high prevalence of chronic HBV infection throughout the world. The overall aim of this study is to determine the sero-prevalence and molecular characterization of hepatitis B virus among HIV positive and HIV negative antenatal women attending Federal Capital Territory Abuja hospitals. A total number of 302 samples were collected from 302 participants between the ages of 18-55 years. The samples were screened for HIV, HBV, HBV serology markers, using rapid test kits, HBV Viral load and HBV genotyping was carried out using multiplex PCR method and data was analyzed using appropriate tools. Nine tested positive for HIV, 34 tested positive for HBV and 2 tested positive for both HIV and HBV, corresponding to 2.9 % (95% CI; 1.2 – 3.8) prevalence for HIV, 11.3% (95% CI; 8.7 – 13.6) for Hepatitis B and 0.7% for HIV/HBV co-infection. Age 25-35 years old had the highest prevalence of HBV 22(7.3%) followed by those of less than 25 years old 8(2.8%) and 1(0.7%) each for age range 36-45 years, 2(0.7%) and 46-55 years. HBeAb and HBcAb were expressed highest among subject within the age range of 25 – 35 year 14 (41.2%) and 22 (64.7 %,) participants respectively, followed by the age range of less than 25 years 5 (14.7%) and 8 (36.4%), for HBeAb and HBcAb respectively. There was no Hepatitis B envelop antigen (HBeAg) nor Hepatitis B surface antibody (HBsAb) among the study group. Of the 34 samples, 20 (62%) had undetectable viral load, while 14 (38%) had detectable viral load. Genotype E was three times more prevalent among those of 25 years old and above than those less than 25 years old detected (75% and 25%). However, genotype B/E mixed was more expressed (60% of cases) among those less than 25 years old, than those greater than 25 years of age (40%). There was no significant difference in the prevalence of genotype E and B/E serotype between HBV+/HIV-patients and their HBV+/HIV+ counterpart (P=0.08 and P=0.15, respectively). HBV Genotype E single infection viral load was significantly (P=0.01) more expressed among those 25 years of age and above than less than 25 years old (4,354,703 ± 346865 IU/ml versus 55.6 ±28.1 IU/ml). Mixed infection genotype B/E was significantly (P=0.04) more expressed among those less than 25 years of age than those 25 years old and above (730.9 ± 238 IU/ml versus IU/ml versus 91.1 ± 48 IU/ml). There was no significant difference between the mean of HBV Viral load HBV+/HIV- patients and their HBV+/HIV+ counterpart (T-test =0.009; P=0.92). In conclusion FCT is 11.3% prevalence rate of HBV and genotypes E and B/E are in circulation among pregnant women among the pregnant women attending antenatal clinic in FCT hospital in Abuja.

Maternal hepatitis B status and Sex at birth: A cross-sectional study in a Ghanaian population

Maternal carrier status of hepatitis B has been associated with excess sons while maternal immunity to it has been associated with excess daughters at birth. However, the proportion of males at birth (sex ratio) is relatively low in Sub-Saharan Africa despite the relatively high prevalence of hepatitis B. However, no known study has tested this hypothesis in the Ghanaian population; hence the aim of the study. The study was cross-sectional between January and September 2023 at the Tamale Central Maternal and Child Health unit. The study involved 380 mothers of whom mothers with daughters (MD) were 145 (38.2 %) while the rest were mothers with sons (MS). The mothers were aged between 18 and 43 years and were sampled within one week of delivery to singleton births. Maternal venous blood samples were collected and tested for hepatitis B surface antigen (HBsAg), surface antibody (HBsAb), envelop antigen (HBeAg) envelope antibody (HBeAb) and core antibody (HBcAb) using immunochromatographic technique and total testosterone (TT), using ELISA. There was no significant difference in the serum total testosterone level between MD and MS (0.32 ± 0.13 vs 0.32 ± 0.27, P = 0.991). Moreover, while the mothers were seropositive for HBsAg (10.5 %), HBsAb (35.5 %), HBeAg (0.0 %), HBeAb (5.3 %) and HBcAb (11.8 %), there was no significant association between sex at birth and maternal hepatitis B status for HBsAg (ꭓ2: 0.531, P = 0.472), HBsAb (ꭓ2: 2.655, P = 0.140), HBeAb (ꭓ2: 0.251, P = 0.633) and HBcAb (ꭓ2: 0.101, P = 1.000). Maternal hepatitis B status may not be associated with the offspring sex at birth in the studied population from Ghana.

Prolonged delivery of HIV-1 vaccine nanoparticles from hydrogels

Immunization is a straightforward concept but remains for some pathogens like HIV-1 a challenge. Thus, new approaches towards increasing the efficacy of vaccines are required to turn the tide. There is increasing evidence that antigen exposure over several days to weeks induces a much stronger and more sustained immune response compared to traditional bolus injection, which usually leads to antigen elimination from the body within a couple of days. Therefore, we developed a poly(ethylene) glycol (PEG) hydrogel platform to investigate the principal feasibility of a sustained release of antigens to mimic natural infection kinetics. Eight-and four-armed PEG macromonomers of different MWs (10, 20, and 40 kDa) were end-group functionalized to allow for hydrogel formation via covalent cross-linking. An HIV-1 envelope (Env) antigen in its trimeric (Envtri) or monomeric (Envmono) form was applied. The soluble Env antigen was compared to a formulation of Env attached to silica nanoparticles (Env-SiNPs). The latter are known to have a higher immunogenicity compared to their soluble counterparts. Hydrogels were tunable regarding the rheological behavior allowing for different degradation times and release timeframes of Env-SiNPs over two to up to 50 days. Affinity measurements of the VCR01 antibody which specifically recognizes the CD4 binding site of Env, revealed that neither the integrity nor the functionality of Envmono-SiNPs (Kd = 2.1 ± 0.9 nM) and Envtri-SiNPs (Kd = 1.5 ± 1.3 nM), respectively, were impaired after release from the hydrogel (Kd before release: 2.1 ± 0.1 and 7.8 ± 5.3 nM, respectively). Finally, soluble Env and Env-SiNPs which are two physico-chemically distinct compounds, were co-delivered and shown to be sequentially released from one hydrogel which could be beneficial in terms of heterologous immunization or single dose vaccination. In summary, this study presents a tunable, versatile applicable, and effective delivery platform that could improve vaccination effectiveness also for other infectious diseases than HIV-1.

Detekcija dobrovoljnog darivatelja krvi s preboljelom infekcijom hepatitisa Bprikaz bolesnice

Introduction: Hepatitis B is liver inflammation caused by the hepatitis B virus, with more than 250 million documented cases worldwide in the chronic form of infection. Markers of hepatitis B infection can be measured in the blood during or after infection and may be present in the form of specific hepatitis B surface antigen (HBsAg) or antibodies to hepatitis B surface (HBs), core (HBc), or envelope (HBe) antigens. Case report: A 42-year-old female, who successfully donated blood for the first time, underwent mandatory serological and molecular testing along with additional testing for other hepatitis B markers. Standard screening showed the absence of HBsAg in the blood, but additional serological testing confirmed the presence of total antibody to hepatitis B core antigen (anti-HBc). Upon repeated reactive results, the sample was sent for confirmatory testing to a reference center. After obtaining all the results, it was determined that the voluntary blood donor had the presence of anti-HB cand HBs antibodies, indicating a prior contact with the hepatitis B virus. While serological tests suggested a resolved hepatitis B infection, the possibility of a persistent liver infection could not be ruled out, despite the absence of detectable hepatitis B virus DNA in the blood. Therefore, the individual has been permanently excluded from the list of potential blood donors. Conclusion: Mandatory serological and molecular testing of blood donors for the hepatitis B virus successfully detects potentially infected individuals and carriers of hepatitis B markers. However, additional testing further enhances the safety of both recipients and blood donors. This case study highlights the importance of comprehensive screening for hepatitis B markers, as relying solely on HBsAg screening would not have identified the voluntary blood donor as a resolved hepatitis B case. Thus, comprehensive screening ensures a higher level of safety in blood transfusion and contributes to overall healthcare protection.

Hepatitis B in Pediatric Population: Observational Retrospective Study in Romania.

Hepatitis B virus (HBV) is a frequent cause of chronic hepatitis worldwide, with an estimated 5.6 million children under 5 years being infected. In Romania, there are no available epidemiology reports on large cohorts in children. We aimed to assess the profile of pediatric chronic HBV infection in southern Romania. We conducted an observational retrospective study on 506 HBV-infected children. Based on alaninaminotransferase (ALT), HBV serology and viremia, we identified four states of the disease. We correlated age, gender, household HBV infection, coinfection with other viruses and laboratory parameters. Most patients were in a positive HBV envelope antigen (HBeAg) immune-active state (65.4%). Age at diagnosis was significantly lower for those with household infection (p < 0.05). ALT values were not significantly different between positive or negative HBeAg patients in the immune-active state (p = 0.780). ALT values were higher in patients with hepatitis D virus (HDV)-associated infection (p < 0.001). Children with a household HBV infection had a high viraemia more frequently when compared to those with no infected relative (79.3% vs. 67.4%) (p < 0.001), but the ALT values were not significantly different (p = 0.21). Most of the patients are in an immune-active state (high ALT, high viremia). The percentages of HBV- and HDV-associated infections are high, but lower than the reported prevalence in Romania in the general population.

Antibody Response to Influenza Hemagglutinin Conserved Stalk Domain after Sequential Immunization with Old Vaccine Strains.

Hemagglutinin (HA) is the major envelope glycoprotein and antigen on the surface of influenza virions. The glycoprotein comprises a globular head and a stalk region. While immunodominant epitopes on influenza HA head are highly variable, the stalk domain is conserved. The variability of the HA head causes the antigenic drift that made the requirement of annual update of vaccine strains. Induction of antibody against the stalk domain has been proposed as an approach for a broadly protective influenza vaccine strategy. Sequential exposure to influenza strains with highly diverse HA heads but conserved stalks have been shown to induce antibody to the low immunogenic stalk domain. Here, we tested this approach by using old influenza vaccine strains that are decades apart in evolution. Inactivated whole virion vaccine of influenza A/Puerto Rico/8/1934, A/USSR/92/1977, and A/Thailand/102/2009 (H1N1) was sequentially immunized into BALB/c mice in comparison to immunization using single strain (A/Thailand/102/2009 (H1N1)). The sequentially immunized mice developed higher levels of binding antibody to the stalk domain. These suggested that using old vaccine strains in sequential vaccination may be a possible approach to induce antibody to the conserved stalk domain.

Hepatic fibrosis among chronic hepatitis B virus-infected patients: North-Western Nigeria experience

Abstract Background: Chronic hepatitis B (CHB) virus infection is a global health problem, affecting two billion individuals worldwide, with 257 million suffering from chronic infection. This condition can lead to severe complications, including fulminant hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Fibrosis serves as the common pathway through which CHB infection progresses to cirrhosis and HCC. Liver biopsy is considered the gold standard assessment method, although it is a procedure that is often avoided. However, the feared complications associated with it can be averted with preventive measures. In this study, we aim to assess the fibrosis pattern among CHB patients using liver biopsy, as well as its tolerability and histological outcome within our locality. Materials and Methods: This was a cross-sectional descriptive study conducted at Aminu Kano Teaching Hospital (AKTH), Kano, Nigeria. Sixty-eight patients with CHB infection were consecutively recruited over a period of 7 months. Following a focused history and physical examination, various tests including complete blood count, liver enzymes, serum proteins, prothrombin time, and international normalized ratio were conducted. A liver biopsy was performed on all eligible consenting subjects without contraindications. The histological findings and results of investigations were recorded and analyzed accordingly. Results: The mean age of the study subjects was 32.43 ± 10.50 years with a male-to-female ratio of 2:1. More than 80% of the patients were negative for HBe antigen (envelope antigen). Out of the 68 patients successfully biopsied, 42 (61.7%) had histological evidence of necroinflammation, with 22% exhibiting significant inflammation. Additionally, 35 patients (56.5%) displayed evidence of fibrosis, with 46.5% of them having significant fibrosis. Conclusion: More than half of the CHB patients examined exhibited evidence of fibrosis and necroinflammation.

Mpox global health emergency: Insights into the virus, immune responses, and advancements in vaccines PART II: Insights into the advancements in vaccines.

Mpox is currently a global health emergency. This review (Part II) aims to provide insights into Mpox vaccines and their advancements, offering easily digestible information for healthcare workers and researchers. Current Mpox vaccines are all live-attenuated, previously approved for smallpox, and are classified into non-replicating (Modified Vaccinia Ankara-Bavarian Nordic or MVA-BN) and replicating vaccines (Lister clone16m8 KM Biologic or LC16m8KMB and Acambis2000 or ACAM2000). Replicating vaccines offer long-lasting immunity but are contraindicated for immunocompromised individuals and those with extensive dermatitis. Replicating vaccines are administered as a single dose via epicutaneous scarification, while the non-replicating vaccine is given as two subcutaneous doses. Regulatory approvals in various countries are based on animal challenge studies, with limited effectiveness data available. Only LC16m8 is approved for children in Japan, while the others are approved for individuals aged 18 and older. Clinical trials are currently investigating the efficacy and safety of MVA-BN, particularly in children and for post-exposure prophylaxis (PEP). Novel Mpox vaccines that provide cross-protection against orthopoxviruses are needed, with DNA, subunit, and mRNA platforms under development. MPXV-neutralizing antibody-inducing target antigens for vaccine development include the outer envelope antigens of extracellular enveloped virus (EEV): A35R and B6R, and the inner membrane antigens of intracellular mature virus (IMV): M1R, A29L, H3L, and E8L. Two mRNA vaccines are currently in early clinical stages. Importantly, the COVID-19 pandemic underscored the importance of addressing vaccine disparities and improving global access. Transformative approaches are being explored to overcome this challenge and to enhance access in low- and middle-income countries.

Characteristics and antiviral treatment eligibility of patients diagnosed with hepatitis B at a teaching hospital in Ghana: Implications for prevention and management.

Hepatitis B virus (HBV) infection poses a considerable public health challenge in limited-resource settings especially in the sub-Saharan African region. Even though HBV infection is incurable, timely treatment is effective in preventing disease progression to liver cirrhosis or hepatocellular carcinoma. However, not all infected patients require treatment. The aim of the study was to determine the clinical, immunological, and virological profiles of treatment naïve patients with HBV infection, seen at the outpatient clinic of the Cape Coast Teaching Hospital. Additionally, the study sought to determine the antiviral treatment eligibility rate based on the 2015 guidelines of the World Health Organization (WHO) compared with the new 2024 guidelines. A hospital-based cross-sectional study involving total sampling of 220 treatment naïve HBV surface antigen positive clients was carried out. A structured questionnaire was used to collect data that were analyzed with STATA version 16. The median age at diagnosis was 34 years (IQR 26.0-41.5) with a male to female ratio of 1:1.5. A total of 138 participants (62.7%) were diagnosed with HBV infection following voluntary testing. There was a median delay of 8.5 months (IQR 3.0-22.5) between initial diagnosis and patients' presentation for medical care. In all, 24 patients (10.9%) had abnormal clinical examination findings, 172 patients (78.2%) had HBV DNA levels ≤ 2000 IU/ml whereas 8 (3.6%) were seropositive for the HBV envelope antigen. A few patients had concomitant human immunodeficiency virus (2.7%) and hepatitis C virus (1.4%) infections. Treatment eligibility rate based on the WHO 2015 guidelines was 6.4% (n = 14), however, with the updated 2024 guidelines, treatment eligibility was 42.3% (n = 93). Increasing the screening rate among the general population, early linkage to clinical care of screen positives and vaccination of screen negatives will help reduce HBV-related clinical conditions in resource-limited settings.

Role of Xenosialylation in Post-Infectious and Post-Vaccination Complications, Including Covid-19 and Anti-SARS-CoV-2 Vaccination.

The host glycosylation mechanism, with sialic acids as a key component, is essential for synthesizing carbohydrate components in viral glycoproteins. We hypothesize a correlation between the presence of the Neu5Gc on the host tissue and the development of infectious complications, adverse vaccine reactions, and autoimmune diseases. In certain mammals, including humans, the loss of the Cytidine Monophospho-N-Acetylneuraminic Acid Hydroxylase gene (negative-CMAH) prevents the synthesis of Neu5Gc, which acts as a Mammalian-associated Carbohydrate Antigen (MCA), (XeSiAs-Neu5Gc). When negative-CMAH species consume products from positive-CMAH mammals or are exposed to non-human cell-derived medicines, Neu5Gc can be integrated into their glycocalyx through a process called xenosialylation, eliciting an inflammatory response (xenosialitis) and prompting the production of circulating anti-Neu5Gc antibodies aimed at eliminating Neu5Gc. We hypothesize that in the case of xenosialylation, neutralizing antiviral antibodies from infections or vaccinations-including those for SARS-CoV-2-may cross-react with the XeSiAs-Neu5Gc glycans, as these resemble viral envelope antigens produced by the host's glycosylation. Additionally, circulating anti-Neu5Gc antibodies may also react with other circulating antibodies, including newly formed antiviral ones with a XeSiAs-Neu5Gc-contaminated Fc region. This can lead to the serum removal of the anti-inflammatory antibodies, leaving only hyperinflammatory IgG agalactosylated antibodies. Such conditions are also seen in various inflammatory and autoimmune diseases. We hypothesize that the combination of antibody cross-reaction and the removal of the XeSiAs-Neu5Gc-contaminated Fc region anti-inflammatory antibodies may intensify severe inflammatory responses like cytokine storms and coagulopathies in COVID-19 patients and those vaccinated. Assessing serum levels of total XeSiAs-Neu5Gc antibodies could be a valuable method for identifying patients at risk of severe complications from viral infections and vaccinations, including SARS-CoV-2. This strategy may also deepen our understanding of the pathogenesis of autoimmune diseases linked to post-infectious and post-vaccination complications, particularly for viruses utilizing the host glycosylation machinery, such as SARS-CoV-2, IAV, EBV, and others.

Prognostic Significance of Alpha-Fetoprotein in Staging of Chronic Hepatitis B Infection

Background Ascertaining the stage of chronic hepatitis-B infection (CHBI) remains one of the major predicaments to effective therapeutic decision. There is pressing need to forestall dearth of such reliable biomarker(s). Despite the promising tendency of alpha-fetoprotein (AFP), it has not been assessed in staging CHBI.ObjectiveThis study was to determine the prognosis of serum AFP as a biomarker for staging CHBI. MethodsParticipants were grouped into three based on their hepatitis-B envelope antigen (HBeAg) status and alanine aminotransferase (ALT) level. By denoting HbeAg(+) as (EP), HbeAg(-) as (EN), elevated ALT as (H) and normal ALT as (I), the stages were EPH, ENH and ENI. AFP was assayed, One-way ANOVA, Multivariate linear regression and area under curve were adopted for the analysis. ResultsAFP was significantly elevated, (P &lt; 0.05) in EPH, which equally has the highest prevalence of elevated AFP (64.7%). After adjusting for confounding factors, odds ratio was 1.438 (95% CI, 0.62–1.948), while area under the curve for predicting EPH was (0.828, 95% CI, 0.778 –0.895).ConclusionsThe finding of elevated AFP in CHBI is an independent prognostic marker of EPH. It is often associated with necroinflammation; thus, it is a reliable indicator for treatment initiation.Rwanda J Med Health Sci 2023;6(3):355-366

NAFLD is associated with less severe liver fibrosis in chronic hepatitis B: A multi-center, retrospective study

Introduction and ObjectivesChronic hepatitis B (CHB) may progress to more serious liver diseases and it is often accompanied by non-alcoholic fatty liver disease (NAFLD). NAFLD and CHB share risk factors for liver fibrosis and cirrhosis, but the influence of NAFLD on fibrosis progression is controversial. This retrospective study evaluated the prevalence of NAFLD in patients with CHB and investigated associations between NAFLD and liver fibrosis in a large multi-center cohort of hepatitis B patients submitted to liver biopsy. Patients and MethodsTreatment-naïve patients with CHB who underwent liver biopsy were analyzed. Propensity score matching (PSM) was performed to adjust the confounders between patients with and without NAFLD. ResultsA total of 1496 CHB patients were included. Two hundred and ninety (19.4%) patients were diagnosed with NAFLD by liver biopsy. The proportions of significant liver fibrosis (52.8% vs. 63.9%, P<0.001), advanced liver fibrosis (27.2% vs. 36.5%, P=0.003), and cirrhosis (13.4% vs. 19.7%, P=0.013) was considerably lower in CHB patients with NAFLD compared to those without NAFLD. 273 patients were included in each group after PSM adjusted for age, sex, hepatitis B envelope antigen status, and hepatitis B virus DNA. Liver fibrosis remained less severe in CHB patients with NAFLD than those without NAFLD (P<0.05) after PSM. The presence of NAFLD was considered an independent negative factor of significant liver fibrosis (odds ratio (OR) 0.692, P=0.013) and advanced liver fibrosis (OR 0.533, P = 0.002) in CHB patients. ConclusionsNAFLD is not uncommon in CHB patients with the prevalence of 19.4%. The presence of NAFLD is associated with less severe liver fibrosis in CHB patients. Registration No. of the study/trialNCT03097952.

Peptide delivery of a multivalent mRNA SARS-CoV-2 vaccine

Lipid nanoparticles (LNP) have been instrumental in the success of mRNA vaccines and have opened up the field to a new wave of therapeutics. However, what is ahead beyond the LNP? The approach herein used a nanoparticle containing a blend of Spike, Membrane and Envelope antigens complexed for the first time with the RALA peptide (RALA-SME). The physicochemical characteristics and functionality of RALA-SME were assessed. With >99% encapsulation, RALA-SME was administered via intradermal injection in vivo, and all three antigen-specific IgG antibodies were highly significant. The IgG2a:IgG1 ratio were all >1.2, indicating a robust TH1 response, and this was further confirmed with the T-Cell response in mice. A complete safety panel of markers from mice were all within normal range, supported by safety data in hamsters. Vaccination of Syrian Golden hamsters with RALA-SME derivatives produced functional antibodies capable of neutralising SARS-CoV-2 from both Wuhan-Hu-1 and Omicron BA.1 lineages after two doses. Antibody levels increased over the study period and provided protection from disease-specific weight loss, with inhibition of viral migration down the respiratory tract. This peptide technology enables the flexibility to interchange and add antigens as required, which is essential for the next generation of adaptable mRNA vaccines.