The global outbreak of clade IIb mpox in 2022-2023 changed our understanding of the epidemiology and prevention of mpox, simultaneously highlighting inequities in access to vaccines, diagnostics, and therapeutics. With the recent multinational spread of clade Ib mpox, it is important to revisit these lessons to improve future response. In September 2024, an international mpox symposium was held at Johns Hopkins University to discuss what we have learned and how to better prepare for the future. Here we highlight perspectives from that meeting and priorities for future mpox research.
{"title":"Mpox: What have we learned and how do we better prepare for the future?","authors":"Seth D Judson, Chloe M Orkin, Kelly Gebo","doi":"10.1093/infdis/jiaf040","DOIUrl":"https://doi.org/10.1093/infdis/jiaf040","url":null,"abstract":"The global outbreak of clade IIb mpox in 2022-2023 changed our understanding of the epidemiology and prevention of mpox, simultaneously highlighting inequities in access to vaccines, diagnostics, and therapeutics. With the recent multinational spread of clade Ib mpox, it is important to revisit these lessons to improve future response. In September 2024, an international mpox symposium was held at Johns Hopkins University to discuss what we have learned and how to better prepare for the future. Here we highlight perspectives from that meeting and priorities for future mpox research.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"94 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chuqi Liu, Yongzhen Guo, Lulu Wang, Ruixia Guo, Dongmei Lei
Background Human papillomavirus (HPV) is a leading cause of cervical cancer, with 14 subtypes classified as high-risk human papillomavirus (HR-HPV). Despite the availability of vaccines, certain regions still experience limited access. Herpes simplex virus type II (HSV-II), a common sexually transmitted infection, is hypothesized to increase the risk of HR-HPV infections. This study aims to individually analyze whether HSV-II infection increases the risk of each high-risk type of HPV infection in a representative sample of American adults. Methods Data were derived from the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2016, involving 4076 female participants. The study utilized logistic regression to estimate the link between HSV-II infection and HR-HPV infection. And we conducted a further stratified analysis to evaluate the impact of HSV-II on HR-HPV infections in different subgroups. Results After adjustment, the odds of having HR-HPV infection were 1.46 (95%CI, 1.24, 1.71) for those with HSV-II infection. Moreover, women with HSV-II infection had higher odds of HPV18 infection (OR=3.01, 95% CI: 2.05, 4.41) and HPV58 (OR=2.05, 95% CI: 1.52, 3.32) infection even after adjusting for potential confounding factors. The results remain significant in subgroup analysis and in the interaction test. Conclusion The study found a significant association between HSV-II infection and HR-HPV infection, particularly with HPV types 18 and 58, highlighting the importance of preventing HSV infection and advocating for early vaccination with HPV vaccine for those vulnerable to HSV infection. Further prospective studies are needed to validate their causal associations and elucidate the underlying mechanisms.
{"title":"Association Between Herpes Simplex Virus Type II and High-Risk Human Papillomavirus Infections: A Population Study of the National Health and Nutrition Examination Survey, 2009-2016","authors":"Chuqi Liu, Yongzhen Guo, Lulu Wang, Ruixia Guo, Dongmei Lei","doi":"10.1093/infdis/jiaf033","DOIUrl":"https://doi.org/10.1093/infdis/jiaf033","url":null,"abstract":"Background Human papillomavirus (HPV) is a leading cause of cervical cancer, with 14 subtypes classified as high-risk human papillomavirus (HR-HPV). Despite the availability of vaccines, certain regions still experience limited access. Herpes simplex virus type II (HSV-II), a common sexually transmitted infection, is hypothesized to increase the risk of HR-HPV infections. This study aims to individually analyze whether HSV-II infection increases the risk of each high-risk type of HPV infection in a representative sample of American adults. Methods Data were derived from the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2016, involving 4076 female participants. The study utilized logistic regression to estimate the link between HSV-II infection and HR-HPV infection. And we conducted a further stratified analysis to evaluate the impact of HSV-II on HR-HPV infections in different subgroups. Results After adjustment, the odds of having HR-HPV infection were 1.46 (95%CI, 1.24, 1.71) for those with HSV-II infection. Moreover, women with HSV-II infection had higher odds of HPV18 infection (OR=3.01, 95% CI: 2.05, 4.41) and HPV58 (OR=2.05, 95% CI: 1.52, 3.32) infection even after adjusting for potential confounding factors. The results remain significant in subgroup analysis and in the interaction test. Conclusion The study found a significant association between HSV-II infection and HR-HPV infection, particularly with HPV types 18 and 58, highlighting the importance of preventing HSV infection and advocating for early vaccination with HPV vaccine for those vulnerable to HSV infection. Further prospective studies are needed to validate their causal associations and elucidate the underlying mechanisms.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ronald J Ellis, Florin Vaida, Keren Hu, Michael Dube, Brook Henry, Felicia Chow, Robert K Heaton, Daniel Lee, Fred Sattler
Background In people with HIV (PWH) who are virally suppressed (VS) on antiretroviral therapy (ART), abdominal obesity (AO) is linked to neurocognitive impairment (NCI), potentially due to visceral adiposity, inflammation, and reduced insulin-like growth factor 1 (IGF-1). Tesamorelin, a growth hormone-releasing hormone, reduces AO and increases IGF-1, suggesting it might mitigate NCI in VS PWH. Methods This 6-month, Phase II randomized, open-label clinical trial compared Tesamorelin versus standard-of-care (SOC) for NCI in abdominally obese PWH. Participants had VS, NCI, and AO (elevated waist circumference [WC]). Exclusions included conditions other than HIV causing NCI, active substance use disorder, and malignancy. Results Seventy-three participants were randomized 3:2 to Tesamorelin or SOC (2mg subcutaneously daily). The primary outcome was the change in neurocognitive performance at 6 months, with secondary outcomes including WC, mood, and daily functioning. The groups were well-matched at baseline. The Tesamorelin group showed a trend toward improved neurocognitive performance after 6 months (mean change: 0.146, 95% CI: -0.002 to 0.294, p=0.060), while the SOC group did not (0.103, 95% CI: -0.095 to 0.301, p=0.295), but the between-group difference was not significant (p=0.673). IGF-1 levels increased, but changes did not correlate with sRCS or WC. The Tesamorelin group had a greater reduction in WC than the SOC group (median difference -2.7 cm, p=0.015). Conclusions While tesamorelin reduced WC, the cognitive benefits did not significantly differ between groups. Recognizing the limitations of insufficient power and no placebo arm, this study suggests no clear benefit of short-term AO reduction with tesamorelin on NCI.
{"title":"Effects of Tesamorelin on Neurocognitive Impairment in Abdominally Obese Persons with HIV","authors":"Ronald J Ellis, Florin Vaida, Keren Hu, Michael Dube, Brook Henry, Felicia Chow, Robert K Heaton, Daniel Lee, Fred Sattler","doi":"10.1093/infdis/jiaf012","DOIUrl":"https://doi.org/10.1093/infdis/jiaf012","url":null,"abstract":"Background In people with HIV (PWH) who are virally suppressed (VS) on antiretroviral therapy (ART), abdominal obesity (AO) is linked to neurocognitive impairment (NCI), potentially due to visceral adiposity, inflammation, and reduced insulin-like growth factor 1 (IGF-1). Tesamorelin, a growth hormone-releasing hormone, reduces AO and increases IGF-1, suggesting it might mitigate NCI in VS PWH. Methods This 6-month, Phase II randomized, open-label clinical trial compared Tesamorelin versus standard-of-care (SOC) for NCI in abdominally obese PWH. Participants had VS, NCI, and AO (elevated waist circumference [WC]). Exclusions included conditions other than HIV causing NCI, active substance use disorder, and malignancy. Results Seventy-three participants were randomized 3:2 to Tesamorelin or SOC (2mg subcutaneously daily). The primary outcome was the change in neurocognitive performance at 6 months, with secondary outcomes including WC, mood, and daily functioning. The groups were well-matched at baseline. The Tesamorelin group showed a trend toward improved neurocognitive performance after 6 months (mean change: 0.146, 95% CI: -0.002 to 0.294, p=0.060), while the SOC group did not (0.103, 95% CI: -0.095 to 0.301, p=0.295), but the between-group difference was not significant (p=0.673). IGF-1 levels increased, but changes did not correlate with sRCS or WC. The Tesamorelin group had a greater reduction in WC than the SOC group (median difference -2.7 cm, p=0.015). Conclusions While tesamorelin reduced WC, the cognitive benefits did not significantly differ between groups. Recognizing the limitations of insufficient power and no placebo arm, this study suggests no clear benefit of short-term AO reduction with tesamorelin on NCI.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Junko Yano, Kimberly Langdon, Michael Swor, Mairi C Noverr, Paul L Fidel
Background Vulvovaginal candidiasis (VVC), caused primarily by Candida albicans, is currently treated with either prescription or over-the-counter antifungal drugs, often with variable efficacy and relapses. New and improved therapeutic strategies, including drug-free treatment alternatives, are needed. Upon overgrowth or environmental triggers, C. albicans yeast transitions into hyphae that results in an aberrant immunopathologic response by neutrophils, contributing to the characteristic vulvovaginal symptoms. The purpose of this study was to evaluate the efficacy of a patented intravaginal cooling device (Vlisse®) to provide symptom relief in women with VVC via putative reversal of C. albicans hyphae to the commensal yeast form, with additional proof of principle in an animal model. Methods This pilot clinical trial involved five women with VVC who used the device twice daily for three days. Vulvovaginal symptoms were monitored and scored for each use, followed by pelvic examination 30 days post-treatment. An established mouse model of VVC, using cooled magnetic micro stir rods for vaginal cooling, was employed to evaluate the effect on fungal morphology and vaginal immunopathology. Results Clinical cure, defined as complete reduction in symptoms without recurrence over a 30-day follow-up period, was achieved in all women. In the mouse model, the insertion of pre-cooled magnetic rods intravaginally for short periods, twice daily for 3 days, reduced the immunopathogenic neutrophil infiltration and hyphal presence. Conclusions Intravaginal cooling treatment provides clinical cure for VVC with strong proof of concept in an accompanying animal model. The therapeutic efficacy of Vlisse® warrants further testing in large-scale long-term clinical trials.
{"title":"Intravaginal cooling provides symptom relief in women with vulvovaginal candidiasis and reduces immunopathology in an accompanying mouse model","authors":"Junko Yano, Kimberly Langdon, Michael Swor, Mairi C Noverr, Paul L Fidel","doi":"10.1093/infdis/jiaf028","DOIUrl":"https://doi.org/10.1093/infdis/jiaf028","url":null,"abstract":"Background Vulvovaginal candidiasis (VVC), caused primarily by Candida albicans, is currently treated with either prescription or over-the-counter antifungal drugs, often with variable efficacy and relapses. New and improved therapeutic strategies, including drug-free treatment alternatives, are needed. Upon overgrowth or environmental triggers, C. albicans yeast transitions into hyphae that results in an aberrant immunopathologic response by neutrophils, contributing to the characteristic vulvovaginal symptoms. The purpose of this study was to evaluate the efficacy of a patented intravaginal cooling device (Vlisse®) to provide symptom relief in women with VVC via putative reversal of C. albicans hyphae to the commensal yeast form, with additional proof of principle in an animal model. Methods This pilot clinical trial involved five women with VVC who used the device twice daily for three days. Vulvovaginal symptoms were monitored and scored for each use, followed by pelvic examination 30 days post-treatment. An established mouse model of VVC, using cooled magnetic micro stir rods for vaginal cooling, was employed to evaluate the effect on fungal morphology and vaginal immunopathology. Results Clinical cure, defined as complete reduction in symptoms without recurrence over a 30-day follow-up period, was achieved in all women. In the mouse model, the insertion of pre-cooled magnetic rods intravaginally for short periods, twice daily for 3 days, reduced the immunopathogenic neutrophil infiltration and hyphal presence. Conclusions Intravaginal cooling treatment provides clinical cure for VVC with strong proof of concept in an accompanying animal model. The therapeutic efficacy of Vlisse® warrants further testing in large-scale long-term clinical trials.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elias Barbosa da Silva-Junior, Victor Guedes de Araujo, Carlla Assis Araujo-Silva, Luciana Polaco Covre, Joyce Cristina Guimarães de Oliveira, Israel Diniz-Lima, Leonardo Freire-de-Lima, Alexandre Morrot, Lycia de Brito-Gitirana, Jose Osvaldo Previato, Lucia Mendonça-Previato, Rossiane Claudia Vommaro, Hilda Petrs-Silva, Debora Decote-Ricardo, Herbert Leonel de Matos Guedes, Celio Geraldo Freire-de-Lima
Cryptococcus gattii is a saprophytic basidiomycete that grows in the environment and can cause systemic cryptococcosis. Ocular cryptococcosis causes blindness and is commonly associated with central nervous system (CNS) infection. Toll-like receptor 9 (TLR9) can control cryptococcosis and another mycosis. Here, using C57BL/6 TLR9 knockout mice (TLR9-/-), we evaluated the role of TLR9 signaling in ocular involvement during systemic C. gattii-infection. We observed ocular impairment and found a high fungal burden in the retina, vitreous humor (VH), and optic nerve (ON) of TLR9-/- mice three weeks after infection. Capsular polysaccharide glucuronoxylomannan (GXM) deposition, astrogliosis and morphological alterations in retina lead to progressive blindness of TLR9-/- mice. The phenomenon observed in our work has not yet been explored in a murine model. These results contribute to the understanding of the role of TLR9 during ocular cryptococcosis. Therapies using TLR9 agonists may be important for the treatment of ocular cryptococcosis.
{"title":"Lack of TLR9 exacerbates ocular impairment and visual loss during systemic Cryptococcus gattii infection","authors":"Elias Barbosa da Silva-Junior, Victor Guedes de Araujo, Carlla Assis Araujo-Silva, Luciana Polaco Covre, Joyce Cristina Guimarães de Oliveira, Israel Diniz-Lima, Leonardo Freire-de-Lima, Alexandre Morrot, Lycia de Brito-Gitirana, Jose Osvaldo Previato, Lucia Mendonça-Previato, Rossiane Claudia Vommaro, Hilda Petrs-Silva, Debora Decote-Ricardo, Herbert Leonel de Matos Guedes, Celio Geraldo Freire-de-Lima","doi":"10.1093/infdis/jiaf034","DOIUrl":"https://doi.org/10.1093/infdis/jiaf034","url":null,"abstract":"Cryptococcus gattii is a saprophytic basidiomycete that grows in the environment and can cause systemic cryptococcosis. Ocular cryptococcosis causes blindness and is commonly associated with central nervous system (CNS) infection. Toll-like receptor 9 (TLR9) can control cryptococcosis and another mycosis. Here, using C57BL/6 TLR9 knockout mice (TLR9-/-), we evaluated the role of TLR9 signaling in ocular involvement during systemic C. gattii-infection. We observed ocular impairment and found a high fungal burden in the retina, vitreous humor (VH), and optic nerve (ON) of TLR9-/- mice three weeks after infection. Capsular polysaccharide glucuronoxylomannan (GXM) deposition, astrogliosis and morphological alterations in retina lead to progressive blindness of TLR9-/- mice. The phenomenon observed in our work has not yet been explored in a murine model. These results contribute to the understanding of the role of TLR9 during ocular cryptococcosis. Therapies using TLR9 agonists may be important for the treatment of ocular cryptococcosis.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael E Pichichero, Eduardo Gonzalez, Andrew Cox, Terri C Thayer, Peter Bajorski
Introduction We sought to explore the variability of antibody responses to multiple vaccines during early life in individual children, assess the trajectory of each child longitudinally, determine the associations of demographic variables and antibiotic exposures with vaccine-induced immunity, and link vaccine responsiveness to infection proneness. Methods In 357 prospectively-recruited children, age six through 36 months, antibody levels to 13 routine vaccine antigens were measured in sera at multiple time points and normalized to their respective protective thresholds to categorize children into four groups: very low, low, normal, and high vaccine responder. Demographic variables and frequency of antibiotic exposure data were collected. Participants were followed to determine change in vaccine groups over time and occurrences of infections. Results Vaccine-induced antibody levels persisted over time as very low, low, normal, or high in individual children and changed post-primary through post-booster immunizations against multiple antigen types, including toxoids, purified proteins, polysaccharide-protein conjugates, recombinant proteins and inactivated viruses. Factors influencing persistence or change in vaccine response group were assessed. Children who did not attend day care and African American/multiracial children had higher vaccine-induced antibody levels than White children. Children with lower vaccine-induced antibody levels had more frequent antibiotic exposures. Low vaccine responsiveness was linked to more frequent antibiotic-treated bacterial infections. Conclusion When vaccine-induced antibody levels are used to define vaccine response groups, individual children may persist or change groups over time, which is associated with demographic variables and influenced by antibiotic exposures. Lower vaccine responsiveness can be linked to more frequent antibiotic-treated bacterial infections.
{"title":"Variability in Vaccine Response and Trajectory in Early Childhood and Association with Demographic Variables, Antibiotic Exposure and Infection Proneness","authors":"Michael E Pichichero, Eduardo Gonzalez, Andrew Cox, Terri C Thayer, Peter Bajorski","doi":"10.1093/infdis/jiaf023","DOIUrl":"https://doi.org/10.1093/infdis/jiaf023","url":null,"abstract":"Introduction We sought to explore the variability of antibody responses to multiple vaccines during early life in individual children, assess the trajectory of each child longitudinally, determine the associations of demographic variables and antibiotic exposures with vaccine-induced immunity, and link vaccine responsiveness to infection proneness. Methods In 357 prospectively-recruited children, age six through 36 months, antibody levels to 13 routine vaccine antigens were measured in sera at multiple time points and normalized to their respective protective thresholds to categorize children into four groups: very low, low, normal, and high vaccine responder. Demographic variables and frequency of antibiotic exposure data were collected. Participants were followed to determine change in vaccine groups over time and occurrences of infections. Results Vaccine-induced antibody levels persisted over time as very low, low, normal, or high in individual children and changed post-primary through post-booster immunizations against multiple antigen types, including toxoids, purified proteins, polysaccharide-protein conjugates, recombinant proteins and inactivated viruses. Factors influencing persistence or change in vaccine response group were assessed. Children who did not attend day care and African American/multiracial children had higher vaccine-induced antibody levels than White children. Children with lower vaccine-induced antibody levels had more frequent antibiotic exposures. Low vaccine responsiveness was linked to more frequent antibiotic-treated bacterial infections. Conclusion When vaccine-induced antibody levels are used to define vaccine response groups, individual children may persist or change groups over time, which is associated with demographic variables and influenced by antibiotic exposures. Lower vaccine responsiveness can be linked to more frequent antibiotic-treated bacterial infections.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Spyros Chalkias, Antionette Pragalos, Adebayo Akinsola, Gary Berman, Madhavi Ampajwala, Jay Meyer, Lorraine Schoch, Wen Zhou, Yamuna D Paila, Weiping Deng, Jing Feng, Elizabeth de Windt, Darin Edwards, Jacqueline Miller, Rituparna Das
Background mRNA-1283 is an investigational COVID-19 mRNA vaccine encoding the receptor-binding and N-terminal domains of the SARS-CoV-2 spike protein in contrast to the original mRNA-1273, which encodes the full-length spike protein. Methods A phase 2a, dose-ranging, observer-blind, randomized study (NCT05137236) conducted in adults (≥18 years) previously vaccinated with mRNA-1273 evaluated the safety and immunogenicity of a single dose of mRNA-1283 (2.5, 5, and 10 µg) and its bivalent formulation, mRNA-1283.211 (5 and 10 µg; encoding original SARS-CoV-2 and Beta) against the comparator mRNA-1273, 50 µg (Part A). A subsequent, open-label study part (Part B) evaluated the safety and immunogenicity of a monovalent Omicron BA.1 vaccine, mRNA-1283.529 (5 and 10 µg). Results A total of 340 participants were randomized in Part A, and 200 participants were enrolled in Part B. All dose levels of mRNA-1283 vaccines were well tolerated and increased the neutralizing antibody (nAb) responses at Day 29 compared to baseline against SARS-CoV-2 D614G and Beta. The nAb responses elicited by mRNA-1283 were higher than those elicited by mRNA-1273. mRNA-1283.529 (Part B) increased nAb at Day 29 against Omicron BA.1. Antibody responses remained detectable for a year post-vaccination. Conclusions mRNA-1283 was well tolerated and exhibited improved immunogenicity compared to mRNA-1273.
{"title":"Safety and Immunogenicity of SARS-CoV-2 Spike Receptor-Binding Domain andN-Terminal Domain mRNA Vaccine","authors":"Spyros Chalkias, Antionette Pragalos, Adebayo Akinsola, Gary Berman, Madhavi Ampajwala, Jay Meyer, Lorraine Schoch, Wen Zhou, Yamuna D Paila, Weiping Deng, Jing Feng, Elizabeth de Windt, Darin Edwards, Jacqueline Miller, Rituparna Das","doi":"10.1093/infdis/jiaf022","DOIUrl":"https://doi.org/10.1093/infdis/jiaf022","url":null,"abstract":"Background mRNA-1283 is an investigational COVID-19 mRNA vaccine encoding the receptor-binding and N-terminal domains of the SARS-CoV-2 spike protein in contrast to the original mRNA-1273, which encodes the full-length spike protein. Methods A phase 2a, dose-ranging, observer-blind, randomized study (NCT05137236) conducted in adults (≥18 years) previously vaccinated with mRNA-1273 evaluated the safety and immunogenicity of a single dose of mRNA-1283 (2.5, 5, and 10 µg) and its bivalent formulation, mRNA-1283.211 (5 and 10 µg; encoding original SARS-CoV-2 and Beta) against the comparator mRNA-1273, 50 µg (Part A). A subsequent, open-label study part (Part B) evaluated the safety and immunogenicity of a monovalent Omicron BA.1 vaccine, mRNA-1283.529 (5 and 10 µg). Results A total of 340 participants were randomized in Part A, and 200 participants were enrolled in Part B. All dose levels of mRNA-1283 vaccines were well tolerated and increased the neutralizing antibody (nAb) responses at Day 29 compared to baseline against SARS-CoV-2 D614G and Beta. The nAb responses elicited by mRNA-1283 were higher than those elicited by mRNA-1273. mRNA-1283.529 (Part B) increased nAb at Day 29 against Omicron BA.1. Antibody responses remained detectable for a year post-vaccination. Conclusions mRNA-1283 was well tolerated and exhibited improved immunogenicity compared to mRNA-1273.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaotian Tang, Qian Yu, Yingjun Cui, Thomas M Hart, Freddie Rivas-Giorgi, Keith Calloway, Amrita Ray Mohapatra, Erol Fikrig
Lyme disease, caused by Borrelia burgdorferi, is transmitted to humans by Ixodes ticks. CCL17 is a potent chemokine that plays important roles in diverse illnesses, including autoimmune and infectious diseases. CCL17 knockout (KO) mice, infected with B. burgdorferi, had a reduced pathogen load in the heart, compared to control animals. Mice lacking CCL17 also showed signs of immune alteration upon B. burgdorferi infection, including diverse serum levels of proinflammatory cytokines and fewer monocytes and macrophages infiltration. CCL17 also interacts directly with B. burgdorferi, the first demonstration that this chemokine has an affinity for a vector-borne pathogen.
{"title":"CCL17 influences Borrelia burgdorferi infection in the heart","authors":"Xiaotian Tang, Qian Yu, Yingjun Cui, Thomas M Hart, Freddie Rivas-Giorgi, Keith Calloway, Amrita Ray Mohapatra, Erol Fikrig","doi":"10.1093/infdis/jiaf011","DOIUrl":"https://doi.org/10.1093/infdis/jiaf011","url":null,"abstract":"Lyme disease, caused by Borrelia burgdorferi, is transmitted to humans by Ixodes ticks. CCL17 is a potent chemokine that plays important roles in diverse illnesses, including autoimmune and infectious diseases. CCL17 knockout (KO) mice, infected with B. burgdorferi, had a reduced pathogen load in the heart, compared to control animals. Mice lacking CCL17 also showed signs of immune alteration upon B. burgdorferi infection, including diverse serum levels of proinflammatory cytokines and fewer monocytes and macrophages infiltration. CCL17 also interacts directly with B. burgdorferi, the first demonstration that this chemokine has an affinity for a vector-borne pathogen.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"67 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jimmy Ma, Raaka G Kumbhakar, Amanda Casto, Eric J Chow, Janet A Englund, Rashi Gautam, Jose Jaimes, Jacqueline E Tate, Sarah Smart, Nandita S Mani, Seth A Cohen, Abby Hussein, Krista Rietberg, Chloe Bryson-Cahn, Ferric C Fang
Rotavirus is a leading cause of diarrhea among children but less known as a cause among adults. We describe clinical, epidemiologic, and genotype characteristics of a rotavirus outbreak among adults in King County, Washington occurring January-June 2023. Adult rotavirus incidence in 2023 was ten times higher than the same period in 2022 (5% versus 0.5% samples). Disease severity was mild. G9P[4], an uncommon, non-vaccine strain in USA, was the predominant genotype. Genotyping suggested spillover from children with subsequent spread among adults. Our study highlights benefits of routine testing and genotyping during outbreaks for surveillance, tracking, and understanding implications on vaccination.
{"title":"Outbreak of Rotavirus Diarrheal Infection among Adults in King County, Washington, January-June 2023","authors":"Jimmy Ma, Raaka G Kumbhakar, Amanda Casto, Eric J Chow, Janet A Englund, Rashi Gautam, Jose Jaimes, Jacqueline E Tate, Sarah Smart, Nandita S Mani, Seth A Cohen, Abby Hussein, Krista Rietberg, Chloe Bryson-Cahn, Ferric C Fang","doi":"10.1093/infdis/jiaf013","DOIUrl":"https://doi.org/10.1093/infdis/jiaf013","url":null,"abstract":"Rotavirus is a leading cause of diarrhea among children but less known as a cause among adults. We describe clinical, epidemiologic, and genotype characteristics of a rotavirus outbreak among adults in King County, Washington occurring January-June 2023. Adult rotavirus incidence in 2023 was ten times higher than the same period in 2022 (5% versus 0.5% samples). Disease severity was mild. G9P[4], an uncommon, non-vaccine strain in USA, was the predominant genotype. Genotyping suggested spillover from children with subsequent spread among adults. Our study highlights benefits of routine testing and genotyping during outbreaks for surveillance, tracking, and understanding implications on vaccination.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Allen Jankeel, Gabriel Pérez-Parra, Anuj K Khetarpal, Ivan A Alvarado, Victor Nizet, George Sakoulas, Erlinda R Ulloa
Background Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with high rates of treatment failure, even when antibiotics showing in vitro susceptibility are used. Early optimization of therapy is crucial to reduce morbidity and mortality. Building on our previous research on carbapenem therapy for methicillin-susceptible S. aureus (MSSA) bacteremia, we examined the utility of adjunctive carbapenems (ertapenem or meropenem) to enhance the efficacy of ceftaroline or vancomycin for treatment of MRSA. Methods The effectiveness of combination therapy versus monotherapy against MRSA was assessed using checkerboard, time-kill, and human whole blood killing assays, as well as a murine bacteremia model. Additionally, we performed transcriptomic analysis and conducted human platelet and antimicrobial peptide killing assays on MRSA pretreated with subtherapeutic concentrations of ceftaroline and carbapenems. The supernatants from these MRSA were used to treat platelets, and cytotoxicity was assessed via LDH release assays. Results Although not typically used for MRSA, we identified striking in vitro and in vivo synergy between carbapenems and ceftaroline or vancomycin. MRSA pretreated with subtherapeutic ceftaroline-carbapenem therapy revealed transcriptional shifts indicative of reduced antibiotic resistance, virulence, and host immune evasion. Supernatants from these MRSA also caused less platelet injury compared to monotherapy. Furthermore, MRSA pretreated with ceftaroline and carbapenems demonstrated increased susceptibility to killing by human platelets and the antimicrobial peptide LL-37. Conclusion The therapeutic success of adjunctive carbapenems appears to be driven by multiple mechanisms, including direct drug-drug synergy with first-line anti-MRSA agents, attenuation of resistance and virulence factors, and enhancement of immune-mediated killing, each warranting further investigation.
{"title":"Enhanced Killing of Methicillin-Resistant Staphylococcus aureus with Ceftaroline or Vancomycin in Combination with Carbapenems","authors":"Allen Jankeel, Gabriel Pérez-Parra, Anuj K Khetarpal, Ivan A Alvarado, Victor Nizet, George Sakoulas, Erlinda R Ulloa","doi":"10.1093/infdis/jiaf010","DOIUrl":"https://doi.org/10.1093/infdis/jiaf010","url":null,"abstract":"Background Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with high rates of treatment failure, even when antibiotics showing in vitro susceptibility are used. Early optimization of therapy is crucial to reduce morbidity and mortality. Building on our previous research on carbapenem therapy for methicillin-susceptible S. aureus (MSSA) bacteremia, we examined the utility of adjunctive carbapenems (ertapenem or meropenem) to enhance the efficacy of ceftaroline or vancomycin for treatment of MRSA. Methods The effectiveness of combination therapy versus monotherapy against MRSA was assessed using checkerboard, time-kill, and human whole blood killing assays, as well as a murine bacteremia model. Additionally, we performed transcriptomic analysis and conducted human platelet and antimicrobial peptide killing assays on MRSA pretreated with subtherapeutic concentrations of ceftaroline and carbapenems. The supernatants from these MRSA were used to treat platelets, and cytotoxicity was assessed via LDH release assays. Results Although not typically used for MRSA, we identified striking in vitro and in vivo synergy between carbapenems and ceftaroline or vancomycin. MRSA pretreated with subtherapeutic ceftaroline-carbapenem therapy revealed transcriptional shifts indicative of reduced antibiotic resistance, virulence, and host immune evasion. Supernatants from these MRSA also caused less platelet injury compared to monotherapy. Furthermore, MRSA pretreated with ceftaroline and carbapenems demonstrated increased susceptibility to killing by human platelets and the antimicrobial peptide LL-37. Conclusion The therapeutic success of adjunctive carbapenems appears to be driven by multiple mechanisms, including direct drug-drug synergy with first-line anti-MRSA agents, attenuation of resistance and virulence factors, and enhancement of immune-mediated killing, each warranting further investigation.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"84 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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