Comparable antibody levels in heterologous and homologous mRNA COVID-19 vaccination, with superior neutralizing and IgA antibody responses in mRNA homologous boosting.

BACKGROUND: Priming with two doses of AZD1222 (Oxford-AstraZeneca; ChAd) followed by a third mRNA vaccine boosting is considered in several countries, yet comparisons between heterologous and homologous booster efficacy remain unexplored. AIM: To evaluate and contrast the immunogenicity of homologous and heterologous boosting regimens. METHOD: The study examined antibody responses in 1113 subjects, comprising 895 vaccine-naïve individuals across different vaccination strategies (partial, primary series, heterologous booster, homologous booster) and 218 unvaccinated, naturally infected individuals. Assessments included neutralizing total antibodies (NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA levels. RESULTS: The study found mRNA vaccines to exhibit superior immunogenicity in primary series vaccination compared to ChAd, with mRNA-1273 significantly enhancing NTAbs, TAbs, anti-S-RBD IgG, and anti-S1 IgA levels (p < 0.001). Both booster types improved antibody levels beyond primary outcomes, with no significant difference in TAbs and anti-S-RBD IgG levels between regimens. However, homologous mRNA boosters significantly outperformed heterologous boosters in enhancing NTAbs and anti-S1 IgA levels, with the BNT/BNT/BNT regimen yielding particularly higher enhancements (p < 0.05). CONCLUSION: The study concludes that although TAbs and anti-S-RBD IgG antibody levels are similar for both regimens, homologous mRNA boosting outperform heterologous regimen by enhancing anti-S1 IgA and neutralizing antibody levels.

Follow-Up and Comparative Assessment of SARS-CoV-2 IgA, IgG, Neutralizing, and Total Antibody Responses After BNT162b2 or mRNA-1273 Heterologous Booster Vaccination.

BACKGROUND: Priming with ChAdOx1 followed by heterologous boosting is considered in several countries. Nevertheless, analyses comparing the immunogenicity of heterologous booster to homologous primary vaccination regimens and natural infection are lacking. In this study, we aimed to conduct a comparative assessment of the immunogenicity between homologous primary vaccination regimens and heterologous prime-boost vaccination using BNT162b2 or mRNA-1273. METHODS: We matched vaccinated naïve (VN) individuals (n = 673) with partial vaccination (n = 64), primary vaccination (n = 590), and primary series plus mRNA vaccine heterologous booster (n = 19) with unvaccinated naturally infected (NI) individuals with a documented primary SARS-CoV-2 infection (n = 206). We measured the levels of neutralizing total antibodies (NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA titers. RESULTS: Homologous primary vaccination with ChAdOx1 not only showed less potent NTAb, TAb, anti-S-RBD IgG, and anti-S1 IgA immune responses compared to primary BNT162b2 or mRNA-1273 vaccination regimens (p < 0.05) but also showed ~3-fold less anti-S1 IgA response compared to infection-induced immunity (p < 0.001). Nevertheless, a heterologous booster led to an increase of ~12 times in the immune response when compared to two consecutive homologous ChAdOx1 immunizations. Furthermore, correlation analyses revealed that both anti-S-RBD IgG and anti-S1 IgA significantly contributed to virus neutralization among NI individuals, particularly in symptomatic and pauci-symptomatic individuals, whereas among VN individuals, anti-S-RBD IgG was the main contributor to virus neutralization. CONCLUSION: The results emphasize the potential benefit of using heterologous mRNA boosters to increase antibody levels and neutralizing capacity particularly in patients who received primary vaccination with ChAdOx1.

Prevalence of hepatitis B and C viruses among migrant workers in Qatar.

Limited data exist on viral hepatitis among migrant populations. This study investigated the prevalence of current hepatitis B virus (HBV) infection and lifetime hepatitis C virus (HCV) infection among Qatar's migrant craft and manual workers (CMWs), constituting 60% of the country's population. Sera collected during a nationwide COVID-19 population-based cross-sectional survey on CMWs between July 26 and September 9, 2020, underwent testing for HBsAg and HCV antibodies. Reactive samples underwent confirmatory testing, and logistic regression analyses were employed to explore associations with HBV and HCV infections. Among 2528 specimens tested for HBV infection, 15 were reactive, with 8 subsequently confirmed positive. Three samples lacked sufficient sera for confirmatory testing but were included in the analysis through multiple imputations. Prevalence of current HBV infection was 0.4% (95% CI 0.2-0.7%). Educational attainment and occupation were significantly associated with current HBV infection. For HCV infection, out of 2607 specimens tested, 46 were reactive, and 23 were subsequently confirmed positive. Prevalence of lifetime HCV infection was 0.8% (95% CI 0.5-1.2%). Egyptians exhibited the highest prevalence at 6.5% (95% CI 3.1-13.1%), followed by Pakistanis at 3.1% (95% CI 1.1-8.0%). Nationality, geographic location, and occupation were significantly associated with lifetime HCV infection. HBV infection is relatively low among CMWs, while HCV infection falls within the intermediate range, both compared to global and regional levels.

Essential bioactive competence of laminarin (ß-glucan)/ laminaran extracted from Padina tetrastromatica and Sargassum cinereum biomass.

Marine algae-based drug discovery has recently received a lot of attention. This study was conducted to extract laminarin-enriched solvent extracts from Padina tetrastromatica and Sargassum cinereum and to evaluate their anticancer activity against the HeLa cell line in vitro (MTT assay). Furthermore, their toxicity was determined through a zebra fish model study. P. tetrastromatica and S. cinereum biomasses have a higher concentration of essential biomolecules such as carbohydrates, protein, and crude fiber, as well as essential minerals (Na, Mg, K, Ca, and Fe) and secondary metabolites. Methanol extracts, in particular, contain a higher concentration of vital phytochemicals than other solvent extracts. The laminarin quantification assay states that methanol extracts of P. tetrastromatica and S. cinereum are rich in laminarin, which is primarily confirmed by FTIR analysis. In an anticancer study, laminarin-MeE from P. tetrastromatica and S. cinereum at concentrations of 750 and 1000 µg mL-1 demonstrated 100% activity against HeLa cells. The Zebra fish model-based toxicity study revealed that the laminarin-enriched MeE of P. tetrastromatica and S. cinereum is non-toxic. These findings revealed that the laminarin-enriched MeE of P. tetrastromatica and S. cinereum has significant anticancer activity without causing toxicity.

Follow up and comparative assessment of IgG, IgA, and neutralizing antibody responses to SARS-CoV-2 between mRNA-vaccinated naïve and unvaccinated naturally infected individuals over 10 months.

BACKGROUND: Evidence on the effectiveness of vaccination-induced immunity compared to SARS-CoV-2 natural immunity is warranted to inform vaccination recommendations. AIM: In this study, we aimed to conduct a comparative assessment of antibody responses between vaccinated naïve (VN) and unvaccinated naturally infected individuals (NI) over 10 Months. METHOD: The study comprised fully-vaccinated naïve individuals (VN; n = 596) who had no history of SARS-CoV-2 infection, and received two doses of either BNT162b2 or mRNA-1273, and naturally infected individuals who had a documented history of SARS-CoV-2 infection and no vaccination record (NI cohort; n = 218). We measured the levels of neutralizing total antibodies (NtAbs), anti-S-RBD IgG, and anti-S1 IgA titers among VN and NI up to ∼10 months from administration of the first dose, and up to ∼7 months from SARS-CoV-2 infection, respectively. To explore the relationship between the antibody responses and time, Spearman's correlation coefficient was computed. Furthermore, correlations between the levels of NtAbs/anti-S-RBD IgG and NtAbs/anti-S1 IgA were examined through pairwise correlation analysis. RESULTS: Up to six months, VN individuals had a significantly higher NtAb and anti-S-RBD IgG antibody responses compared to NI individuals. At the 7th month, there was a significant decline in antibody responses among VN individuals, but not NI individuals, with a minimum decrease of 3.7-fold (p < 0.001). Among VN individuals, anti-S1 IgA levels began to decrease significantly (1.4-fold; p = 0.007) after two months, and both NtAb and S-RBD IgG levels began to decline significantly (NtAb: 2.0-fold; p = 0.042, S-RBD IgG: 2.4-fold; p = 0.035) after three months. After 10 months, the most significant decline among VN individuals was observed for S-RBD-IgG (30.0-fold; P < 0.001), followed by NtAb (15.7-fold; P < 0.001) and S-IgA (3.7-fold; P < 0.001) (most stable). Moreover, after 5 months, there was no significant difference in the IgA response between the two groups. CONCLUSION: These findings have important implications for policymakers in the development of vaccination strategies, particularly in the consideration of booster doses to sustain long-lasting protection against COVID-19.

Seroprevalence of herpes simplex virus type 1 and type 2 among the migrant workers in Qatar.

BACKGROUND: Limited data exists on herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections in migrant populations. This study investigated HSV-1 and HSV-2 seroprevalences and associations among craft and manual workers (CMWs) in Qatar who constitute 60% of Qatar's population. METHODS: A national population-based cross-sectional seroprevalence survey was conducted on the CMW population, all men, between July 26 and September 9, 2020. 2,612 sera were tested for anti-HSV-1 IgG antibodies using HerpeSelect 1 ELISA IgG kits and for anti-HSV-2 IgG antibodies using HerpeSelect 2 ELISA IgG kits (Focus Diagnostics, USA). Univariable and multivariable logistic regression analyses were conducted to identify associations with HSV-1 and HSV-2 infections. RESULTS: Serological testing identified 2,171 sera as positive, 403 as negative, and 38 as equivocal for HSV-1 antibodies, and 300 sera as positive, 2,250 as negative, and 62 as equivocal for HSV-2 antibodies. HSV-1 and HSV-2 seroprevalences among CMWs were estimated at 84.2% (95% CI 82.8-85.6%) and 11.4% (95% CI 10.1-12.6%), respectively. HSV-1 infection was associated with nationality, educational attainment, and occupation. HSV-2 infection was associated with age, nationality, and educational attainment. CONCLUSIONS: Over 80% of CMWs are infected with HSV-1 and over 10% are infected with HSV-2. The findings highlight the need for sexual health programs to tackle sexually transmitted infections among the CMW population.

Treatment with decitabine induces the expression of stemness markers, PD-L1 and NY-ESO-1 in colorectal cancer: potential for combined chemoimmunotherapy.

BACKGROUND: The mechanism of tumor immune escape and progression in colorectal cancer (CRC) is widely investigated in-vitro to help understand and identify agents that might play a crucial role in response to treatment and improve the overall survival of CRC patients. Several mechanisms of immune escape and tumor progression, including expression of stemness markers, inactivation of immunoregulatory genes by methylation, and epigenetic silencing, have been reported in CRC, indicating the potential of demethylating agents as anti-cancer drugs. Of these, a chemotherapeutic demethylating agent, Decitabine (DAC), has been reported to induce a dual effect on both DNA demethylation and histone changes leading to an increased expression of target biomarkers, thus making it an attractive anti-tumorigenic drug. METHODS: We compared the effect of DAC in primary 1076 Col and metastatic 1872 Col cell lines isolated and generated from patients' tumor tissues. Both cell lines were treated with DAC, and the expression of the NY-ESO-1 cancer-testis antigen, the PD-L1 immunoinhibitory marker, and the CD44, Nanog, KLF-4, CD133, MSI-1 stemness markers were analyzed using different molecular and immunological assays. RESULTS: DAC treatment significantly upregulated stemness markers in both primary 1076 Col and meta-static 1872 Col cell lines, although a lower effect occurred on the latter: CD44 (7.85 fold; ***p = 0.0001 vs. (4.19 fold; *p = 0.0120), Nanog (4.1 fold; ***p < 0.0001 vs.1.69 fold; ***p = 0.0008), KLF-4 (4.33 fold; ***p < 0.0001 vs.2.48 fold; ***p = 0.0005), CD133 (16.77 fold; ***p = 0.0003 vs.6.36 fold; *p = 0.0166), and MSI-1 (2.33 fold; ***p = 0.0003 vs.2.3 fold; ***p = 0.0004), respectively. Interestingly, in the metastatic 1872 Col cells treated with DAC, the expression of both PD-L1 and NY-ESO-1 was increased tenfold (*p = 0.0128) and fivefold (***p < 0.0001), respectively. CONCLUSIONS: We conclude that the upregulation of both stemness and immune checkpoint markers by DAC treatment on CRC cells might represent a mechanism of immune evasion. In addition, induction of NY-ESO-1 may represent an immuno-therapeutic option in metastatic CRC patients. Finally, the combination of DAC and anti-PD-1/anti-PD-L1 antibodies treatment should represent a potential therapeutic intervention for this group of patients.

Assessment of the Neutralizing Antibody Response of BNT162b2 and mRNA-1273 SARS-CoV-2 Vaccines in Naïve and Previously Infected Individuals: A Comparative Study.

The currently authorized mRNA COVID-19 vaccines, Pfizer-BNT162b2 and Moderna-mRNA-1273, offer great promise for reducing the spread of the COVID-19 by generating protective immunity against SARS-CoV-2. Recently, it was shown that the magnitude of the neutralizing antibody (NAbs) response correlates with the degree of protection. However, the difference between the immune response in naïve mRNA-vaccinated and previously infected (PI) individuals is not well studied. We investigated the level of NAbs in naïve and PI individuals after 1 to 26 (median = 6) weeks of the second dose of BNT162b2 or mRNA-1273 vaccination. The naïve mRNA-1273 vaccinated group (n = 68) generated significantly higher (~2-fold, p ≤ 0.001) NAbs than the naïve BNT162b2 (n = 358) group. The P -vaccinated group (n = 42) generated significantly higher (~3-fold; p ≤ 0.001) NAbs levels than the naïve-BNT162b2 (n = 426). Additionally, the older age groups produced a significantly higher levels of antibodies than the young age group (<30) (p = 0.0007). Our results showed that mRNA-1273 generated a higher NAbs response than the BNT162b2 vaccine, and the PI group generated the highest level of NAbs response regardless of the type of vaccine.

TRPV2: A Cancer Biomarker and Potential Therapeutic Target.

The Transient Receptor Potential Vanilloid type-2 (TRPV2) channel exhibits oncogenicity in different types of cancers. TRPV2 is implicated in signaling pathways that mediate cell survival, proliferation, and metastasis. In leukemia and bladder cancer, the oncogenic activity of TRPV2 was linked to alteration of its expression profile. In multiple myeloma patients, TRPV2 overexpression correlated with bone tissue damage and poor prognosis. In prostate cancer, TRPV2 overexpression was associated with the castration-resistant phenotype and metastasis. Loss or inactivation of TRPV2 promoted glioblastoma cell proliferation and increased resistance to CD95-induced apoptotic cell death. TRPV2 overexpression was associated with high relapse-free survival in triple-negative breast cancer, whereas the opposite was found in patients with esophageal squamous cell carcinoma or gastric cancer. Another link was found between TRPV2 expression and either drug-induced cytotoxicity or stemness of liver cancer. Overall, these findings validate TRPV2 as a prime candidate for cancer biomarker and future therapeutic target.

Cutaneous manifestations of internal malignancy.

BACKGROUND: Many malignancies affecting the internal organs display cutaneous manifestations which may be either specific (tumor metastases) or nonspecific lesions. AIMS: The study is aimed at determining the frequency and significance of cutaneous manifestations among patients with internal malignancy. MATERIALS AND METHODS: 750 cases of proven internal malignancy, who attended a cancer chemotherapy center in South India, were studied. Specific infiltrates were confirmed by histopathology, fine needle aspiration cytology (FNAC) and marker studies. RESULTS: Out of the 750 patients with internal malignancy, skin changes were seen in a total of 52 (6.93%) patients. CONCLUSION: Cutaneous metastases (specific lesions) were seen in 20 patients (2.66%): contiguous in 6 (0.8%), and non-contiguous in 14 (1.86%). Nonspecific skin changes were seen in 32 patients (4.26%). None of our patients presented with more than one type of skin lesions. Herpes zoster was the most common nonspecific lesion noticed in our patients, followed by generalized pruritus, multiple eruptive seborrheic keratoses, bullous disorder, erythroderma, flushing, purpura, pyoderma gangrenosum, insect bite allergy and lichenoid dermatitis.

Olmsted syndrome: report of two cases.

Olmsted syndrome is an uncommon genetic disorder with symmetrical, diffuse, transgredient, mutilating palmoplantar keratoderma and periorificial hyperkeratosis. Olmsted syndrome in a female patient is particularly rare, and we report two unrelated female patients of Olmsted syndrome, who presented with perioral hyperkeratosis and palmoplantar keratoderma. One of our patients also had woolly hair from birth and flexion contracture of a digit, while the other had pseudoainhum. There was no cardiac involvement. Hence, the diagnosis of Olmsted syndrome was made.

Alkaptonuria.

A case of alkaptonuria, a rare disorder with autosomal recessive inheritance, is reported here. The patient had palmar pigmentation in addition to the usual features of alkaptonuria.

Rare association of hyper IgE syndrome with cervical rib and natal teeth.

Hyper IgE syndrome (HIES) is a rare immunodeficiency syndrome characterized by a triad of cutaneous abscesses, mostly caused by Staphylococus aureus; pneumonia; and raised IgE levels. Nonimmunological associations include course facial features, multiple bone fractures, joint hyperextensibility, and retained primary dentition. Patients require long-term antibiotic therapy. We report here a classical case of HIES with rare associations of natal teeth, bilateral cervical ribs, and conductive deafness. The patient was being treated with monteleukast and dapsone.

White piedra in a mother and daughter.

White Piedra is a superficial fungal infection of the hair caused by Trichosporon asahii. It is also known as trichomycosis nodosa or trichomycosis nodularis. We report two cases of White Piedra in a mother and her daughter for the rarity of such occurrence.

Juvenile dermatomyositis associated with lipodystrophy.

Lipodystrophy and associated metabolic abnormalities are being increasingly recognized as complications of juvenile dermatomyositis. We report one such case.

Klippel-Trenaunay syndrome associated with pseudo-Kaposi's sarcoma.

Pseudo Kaposi's sarcoma is a rare vascular lesion, usually associated with arterio venous malformations of the Parker Weber type, and only occasionally with Klippel Trenaunay syndrome per se. We report one such case.