Browsing by Author "Lerdsamran H."

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    A novel film spray containing curcumin inhibits SARS-CoV-2 and influenza virus infection and enhances mucosal immunity
    (2024-12-01) Nittayananta W.; Lerdsamran H.; Chutiwitoonchai N.; Promsong A.; Srichana T.; Netsomboon K.; Prasertsopon J.; Kerdto J.; Nittayananta W.; Mahidol University
    Background: Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and influenza virus is still a major worldwide health concern. Plants are a good source of bioactive compounds to be used as preventive measures for both inhibiting the virus binding and enhancing mucosal innate immunity. Curcumin has been shown to possess antiviral activity and modulate innate immunity. Therefore, the purpose of this study was to develop an oro-nasal film spray containing curcumin and determine its antiviral activity against SARS-CoV-2 and influenza virus infection, as well as its effects on mucosal innate immunity and inflammatory cytokines in vitro. Methods: The antiviral activity of the film spray against SARS-CoV-2, influenza A/H1N1, A/H3N2, and influenza B was assessed in vitro by plaque reduction assay. Cytotoxicity of the film spray to oral keratinocytes and nasal epithelial cells was assessed by MTT assay, and cytotoxicity to Vero and MDCK cells was assessed by an MTS-based cytotoxicity assay. Oral and nasal innate immune markers in response to the film spray were determined by ELISA and by a commercial Milliplex Map Kit, respectively. Results: Our data show that the film spray containing curcumin can inhibit both SARS-CoV-2 and influenza virus infections while maintaining cell viability. Results obtained among 4 viruses revealed that curcumin film spray demonstrated the highest inhibitory activity against SARS-CoV-2 with the lowest EC50 of 3.15 µg/ml and the highest SI value of 4.62, followed by influenza B (EC50 = 6.32 µg/ml, SI = 2.04), influenza A/H1N1 (EC50 = 7.24 µg/ml, SI = 1.78), and influenza A/H3N2 (EC50 > 12.5 µg/ml, SI < 1.03), respectively. Antimicrobial peptides LL-37 and HD-5, IL-6 and TNF-α produced by oral keratinocytes were significantly induced by the film spray, while hBD2 was significantly reduced. Conclusion: Film spray containing curcumin possesses multiple actions against SARS-CoV-2 infection by inhibiting ACE-2 binding in target cells and enhancing mucosal innate immunity. The film spray can also inhibit influenza virus infection. Therefore, the curcumin film spray may be effective in preventing the viral infection of both SARS-CoV-2 and influenza.
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    Antiviral effect in association with anti-apoptosis and anti-autophagy of repurposing formoterol fumarate dihydrate on enterovirus A71-infected neuronal cells
    (2022-04-02) Jintana K.; Prasertsopon J.; Puthavathana P.; Lerdsamran H.; Mahidol University
    Objective: To investigate antiviral activity, anti-apoptosis and anti-autophagy associated with antiviral effect of repurposing formoterol fumarate dihydrate (FFD) against enterovirus A71 (EV-A71) infection in human neuroblastoma cells. Methods: In vitro antiviral effects of FFD against EV-A71 infection were examined in human neuroblastoma SK-N-SH cells. The impacts on EV-A71 replication were evaluated by progeny virus production, viral RNA synthesis, and viral protein expression. The target of action of FFD against EV-A71 was determined from the effective stage by time-of-addition assay. Moreover, the anti-apoptosis and anti-autophagy activities associated with antiviral effect were observed by detection of apoptosis- and autophagy-related proteins. Results: FFD significantly inhibited EV-A71 replication in neuronal cells through interfering the early stages of replication cycle which might be the steps during uncoating to viral protein synthesis. Additionally, FFD culminated in reducing of EV-A71-induced apoptosis and autophagy with caspase-3-cleaved form and LC3-II expression levels showed markedly decreased while increasing of Bcl-2 and mTOR expression levels. These might indicate the neuroprotective effect of FFD on EV-A71-induced apoptosis and autophagy. Conclusions: Preliminary mode of action studies showed that repurposing FFD significantly inhibited EV-A71 replication at early stage of viral replication and exhibited anti-apoptosis and anti-autophagy activities in neuronal cells. These findings may provide an opportunity, via drug repurposing of FFD, for a candidate antiviral drug against EV-A71 infection.
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    Higher correlation between neutralizing antibodies and surrogate neutralizing or binding antibodies in COVID-19 patients than vaccine recipients
    (2024-04-01) Lerdsamran H.; Anusorntanawat R.; Sangsiriwut K.; Sawadpongpan S.; Prasertsopon J.; Thinpan N.; Intalapaporn P.; Techasuwanna R.; Okada P.; Puthavathana P.; Lerdsamran H.; Mahidol University
    This study determined the seropositive rates and levels of antibodies to severe acute respiratory syndrome coronavirus-2 in 50 patients and 108 vaccinees using microneutralization test (MNT), surrogate virus neutralization test (sVNT), chemiluminescent microparticle immunoassay (CMIA), and electrochemiluminescence immunoassay (ECLIA). MNT, as the reference method, employed living clade S and Delta viruses to measure neutralizing (NT) antibodies, while sVNT employed wild type strain and Delta receptor-binding domains (RBD) as the test antigens to measure sVNT antibodies. CMIA and ECLIA employed only one version of RBD to measure the binding antibodies. Our study performed S gene sequencing of the test virus to exclude undesired mutants that might lead to changes in antibody levels in MNT assay. We showed that spike protein amino acid sequences of our Delta virus contained 13 amino acid changes, with 3 related to the reduced neutralization. The MNT assay showed a significant reduction in seropositive rates and antibody levels in the patients’ sera when the Delta variant replaced clade S as the test virus. In contrast, the seropositive rates determined by sVNT assay using wild type strain RBD and Delta RBD were non-significantly different, suggesting that sVNT assay could not identify the difference between the antigenicity of wild type RBD and Delta RBD. Furthermore, the correlation between the levels of NT and sVNT antibodies was moderate with the patients’ sera but modest with the post-vaccination sera. The seropositive rates in the patients, as determined by CMIA or ECLIA, were not different from the MNT assay using clade S, but not Delta, as the test virus. In all analyses, the correlations between the antibody levels measured by MNT and the other 3 assays were modest to moderate, with the r-values of 0.3500–0.7882.
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    Intranasal Administration of Bivalent RBD Nanoparticles Elicits Strong Systemic Responses That Effectively Block Distal Dissemination of COVID-19
    (2025-01-01) Seesen M.; Sunintaboon P.; Limthongkul J.; Janhirun Y.; Lerdsamran H.; Wiriyarat W.; Ubol S.; Jearanaiwitayakul T.; Seesen M.; Mahidol University
    The intranasal vaccine against coronavirus disease 2019 (COVID-19) has gained more attention because of its ability to induce both mucosal and systemic immune responses. We have recently developed a c-GAMP-adjuvanted bivalent receptor-binding domain (RBD) vaccine, derived from the ancestral strain and the Omicron variant. We demonstrated here that intranasal administration of this vaccine candidate triggers not only the respiratory but also the systemic immune response against SARS-CoV-2. The immunized mice elicited the broadly neutralizing antibodies against the ancestral strain (Wuhan-1) and variants of concern (Delta, Omicron BA.1, and Omicron BA.5). This route of vaccination also induced potent systemic T cell responses with strong cytotoxic activity against both the Wuhan-1 and Omicron BA.1 strains. Additionally, intranasally immunized mice significantly suppressed SARS-CoV-2 RNA levels in circulation and spleens, indicating effective containment of the virus beyond the respiratory tract. These findings suggest that the intranasal bivalent RBD vaccine holds promise for combating SARS-CoV-2 infections.
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    Intranasal immunization with the bivalent SARS-CoV-2 vaccine effectively protects mice from nasal infection and completely inhibits disease development
    (2024-01-01) Jearanaiwitayakul T.; Sunintaboon P.; Kittiayuwat A.; Limthongkul J.; Wathanaphol J.; Janhirun Y.; Lerdsamran H.; Wiriyarat W.; Ubol S.; Jearanaiwitayakul T.; Mahidol University
    With the continuous emergence of coronavirus disease 2019 (COVID-19) waves, the scientific community has developed a vaccine that offers broad-spectrum protection at virus-targeted organs for inhibiting the transmission and protection of disease development. In the present study, a bivalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine containing receptor-binding domain (RBD) protein of spike from Wuhan-1 and omicron BA.1 loaded in nanoparticles, bivalent RBD NPs, was developed. The immunogenicity and protective efficacy of this vaccine candidate were evaluated using an in vivo model. Results showed that mice that received intranasal cGAMP-adjuvanted bivalent RBD-NPs vaccine elicited robust and durable antibody responses. The stimulated antibody broadly neutralized the ancestral strain and variants of concerns (delta and omicron BA.1) in the upper and lower respiratory tracts. Furthermore, the immunized mice developed T-cell response in their lung tissue. Importantly, intranasal immunization with this vaccine candidate efficiently protected mice from nasal infection caused by both Wuhan-1 and BA.1 viruses. Immunized mice that remained susceptible to nasal infection did not develop any symptoms. This is because activated responses in the nasal cavity significantly suppressed virus production. Another word is this nasal vaccine completely protected the mice from disease development and mortality. Therefore, the bivalent RBD vaccine platform has potential to be developed into an anti-SARS-CoV-2 universal vaccine.
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    Measuring SARS-CoV-2 RNA in Bangkok wastewater treatment plants and estimating infected population after fully opening the country in 2023, Thailand
    (2025-12-01) Saita T.; Thitanuwat B.; Niyomdecha N.; Prasertsopon J.; Lerdsamran H.; Puthavathana P.; Noisumdaeng P.; Saita T.; Mahidol University
    Wastewater-based epidemiology (WBE) has been employed for monitoring the presence of SARS-CoV-2 infected population. Herein, the study aims to apply the WBE for surveillance and monitoring SARS-CoV-2 in Bangkok, where the highest official covid-19 cases reported in Thailand, during the fully opening for international tourists in early 2023. A total of 200 wastewater samples (100 influent and 100 effluent samples) were collected from 10 wastewater treatment plants (WWTPs) during January–May 2023. SARS-CoV-2 RNA was detected by real time qRT-PCR with accounting for 51% (102/200). Of these, 88% (88/100) and 14% (14/100) were detected in influent and effluent samples, respectively. The SARS-CoV-2 RNA concentration was detected in ranged of 4.76 × 102–1.48 × 105 copies/L. The amount of SARS-CoV-2 RNA has increased approximately 4 times from the lag phase (January–March) to the log phase (April–May). Spearman’s correlation coefficient revealed that correlation between estimated infected population and weekly reported cases was statistically significant (p-value = 0.017). SARS-CoV-2 RNA in influent had a statistically significant relationship with weekly reported cases (r = 0.481, p-value < 0.001). Lag time analysis revealed early warning 1–3 weeks before rising covid-19 cases observed. GIS was applied for spatial-temporal analysis at the province level, suggesting real time dashboard should be further developed.
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    Phenotypic and functional changes of T cell subsets after CoronaVac vaccination
    (2022-11-15) Phoksawat W.; Nithichanon A.; Lerdsamran H.; Wongratanacheewin S.; Meesing A.; Pipattanaboon C.; Kanthawong S.; Aromseree S.; Yordpratum U.; Laohaviroj M.; Lulitanond V.; Chareonsudjai S.; Puthavathana P.; Kamuthachad L.; Kamsom C.; Thapphan C.; Salao K.; Chonlapan A.; Nawawishkarun P.; Prasertsopon J.; Overgaard H.J.; Edwards S.W.; Phanthanawiboon S.; Mahidol University
    Background: The pandemic coronavirus disease 2019 (COVID-19) is a major global public health concern and several protective vaccines, or preventive/therapeutic approaches have been developed. Sinovac-CoronaVac, an inactivated whole virus vaccine, can protect against severe COVID-19 disease and hospitalization, but less is known whether it elicits long-term T cell responses and provides prolonged protection. Methods: This is a longitudinal surveillance study of SARS-CoV-2 receptor binding domain (RBD)-specific IgG levels, neutralizing antibody levels (NAb), T cell subsets and activation, and memory B cells of 335 participants who received two doses of CoronaVac. SARS-CoV-2 RBD-specific IgG levels were measured by enzyme-linked immunosorbent assay (ELISA), while NAb were measured against two strains of SARS-CoV-2, the Wuhan and Delta variants. Activated T cells and subsets were identified by flow cytometry. Memory B and T cells were evaluated by enzyme-linked immune absorbent spot (ELISpot). Findings: Two doses of CoronaVac elicited serum anti-RBD antibody response, elevated B cells with NAb capacity and CD4+ T cell-, but not CD8+ T cell-responses. Among the CD4+ T cells, CoronaVac activated mainly Th2 (CD4+ T) cells. Serum antibody levels significantly declined three months after the second dose. Interpretation: CoronaVac mainly activated B cells but T cells, especially Th1 cells, were poorly activated. Activated T cells were mainly Th2 biased, demonstrating development of effector B cells but not long-lasting memory plasma cells. Taken together, these results suggest that protection with CoronaVac is short-lived and that a third booster dose of vaccine may improve protection.
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    Safety and immunogenicity of locally produced trivalent inactivated influenza vaccine (Tri Fluvac) in healthy Thai adults aged 18–64 years in Nakhon Phanom: A Phase III double blinded, three-arm, randomized, controlled trial
    (2023-01-01) Prasert K.; Praphasiri P.; Lerdsamran H.; Nakphook S.; Ditsungnoen D.; Chawalchitiporn S.; Sornwong K.; Poopipatpol K.; Wirachwong P.; Narakorn P.; Surichan S.; Suthepakul N.; Thangsupanimitchai N.; Pittayawonganon C.; Puthavathana P.; Davis W.W.; Mott J.A.; Olsen S.J.; Patumanond J.; Mahidol University
    Background: Domestic influenza vaccine production facilitates a sustainable supply for mitigating seasonal influenza and improves national health security by providing infrastructure and experience for pandemic vaccine production, if needed. Methods: A Phase III, double blind, randomized controlled trial was conducted from Sep 2019-Oct 2020 in healthy adults 18–64 years in Nakhon Phanom, Thailand. Randomization (3:3:1) compared study vaccine (Tri Fluvac), saline placebo, and an active comparator (licensed vaccine). Primary outcomes were superior efficacy compared to placebo based on RT-PCR-confirmed influenza virus infection within 12 months and non-inferiority compared to active comparator based on immunogenicity (HAI assay) at 28 days. Safety was also assessed. Results: The trial enrolled 4,284 participants (Tri Fluvac = 1,836; placebo = 1,836; active comparator = 612). There were 29 RT-PCR positive influenza infections (10 Tri Fluvac, 5.5/1,000 PY; 19 placebo, 10.4/1,000PY; 0 comparator) for an absolute protective efficacy of 46.4 (95 % CI = −22.0–76.5) compared with placebo, but the power was 43.7 %. Seroconversion difference rates between Tri Fluvac and comparator at Day 28 were 1.74 (95 % CI: −2.77, 6.25), 2.22 (−2.40, 6.84), and −0.57 (−5.41, 4.27) for A(H1N1), A(H3N2), and B strains, respectively. Adverse and severe adverse events occurred in 175 (9.5 %) Tri Fluvac, 177 (10.8 %) placebo, and 66 (10.8 %) comparator arms (p-value = 0.437, Tri Fluvac vs. comparator) Conclusions: Tri Fluvac was well tolerated, and immunogenicity was non-inferior to the active comparator, meeting U.S. Food and Drug Administration (FDA) criteria for adult vaccine licensure. Few acute respiratory infections were reported during intense COVID-19 pandemic restrictions, resulting in insufficient power to evaluate clinical efficacy.
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    Seroprevalence of anti-SARS-CoV-2 antibodies in Thai adults during the first three epidemic waves
    (2022-04-01) Lerdsamran H.; Mungaomklang A.; Iamsirithaworn S.; Prasertsopon J.; Wiriyarat W.; Saritsiri S.; Anusorntanawat R.; Siriyakorn N.; Intalapaporn P.; Sirikhetkon S.; Sangsiriwut K.; Dangsakul W.; Sawadpongpan S.; Thinpan N.; Kitidee K.; Okada P.; Techasuwanna R.; Mongkalangoon N.; Prasert K.; Puthavathana P.; Mahidol University
    This study determined the presence of anti-SARS-CoV-2 antibodies in 4964 individuals, comprising 300 coronavirus disease-19 (COVID-19) prepandemic serum samples, 142 COVID-19 patients, 2113 individuals at risk due to their occupations, 1856 individuals at risk due to sharing workplaces or communities with COVID-19 patients, and 553 Thai citizens returning after spending extended periods of time in countries with a high disease prevalence. We recruited participants between May 2020 and May 2021, which spanned the first two epidemic waves and part of the third wave of the COVID-19 outbreaks in Thailand. Their sera were tested in a microneutralization and a chemiluminescence immunoassay for IgG against the N protein. Furthermore, we performed an immunofluorescence assay to resolve discordant results between the two assays. None of the prepandemic sera contained anti-SARS-CoV-2 antibodies, while antibodies developed in 88% (15 of 17) of the COVID-19 patients at 8–14 days and in 94–100% of the patients between 15 and 60 days after disease onset. Neutralizing antibodies persisted for at least 8 months, longer than IgG antibodies. Of the 2113 individuals at risk due to their occupation, none of the health providers, airport officers, or public transport drivers were seropositive, while antibodies were present in 0.44% of entertainment workers. Among the 1856 individuals at risk due to sharing workplaces or communities with COVID-19 patients, seropositivity was present in 1.9, 1.5, and 7.5% of the Bangkok residents during the three epidemic waves, respectively, and in 1.3% of the Chiang Mai people during the first epidemic wave. The antibody prevalence varied between 6.5 and 47.0% in 553 Thai people returning from high-risk countries. This serosurveillance study found a low infection rate of SARS-CoV-2 in Thailand before the emergence of the Delta variant in late May 2021. The findings support the Ministry of Public Health’s data, which are based on numbers of patients and contact tracing.