Safety and immunogenicity of an mRNA-based RSV vaccine in Japanese older adults aged ≥60 years: A phase 1, randomized, observer-blind, placebo-controlled trial

Article

作者: Reuter, Caroline ; Panozzo, Catherine A ; Shaw, Christine A ; Kapoor, Archana ; Chen, Grace L. ; Wilson, Eleanor ; Wilson, Lauren ; Chen, Grace L ; Mills, Anthony ; Fitz-Patrick, David ; Panozzo, Catherine A. ; Mihara, Hanako ; Simorellis, Alana K. ; Guo, Ruiting ; Goswami, Jaya ; Shaw, Christine A. ; Stoszek, Sonia K. ; Dhar, Rakesh ; Simorellis, Alana K ; Stoszek, Sonia K ; Mithani, Runa

BACKGROUNDRespiratory syncytial virus (RSV) represents a global health concern, including in older adults. This study assessed the safety and immunogenicity of mRNA-1345, an investigational mRNA RSV vaccine, in adults aged ≥60 years of Japanese descent.METHODSIn this phase 1, randomized, observer-blind, placebo-controlled study, participants were randomized to receive one injection of mRNA-1345 100 μg or placebo. Solicited local and systemic adverse reactions (ARs) were collected within 7 days following injection. Unsolicited adverse events (AEs) were collected up to 28 days after injection; AEs of special interest, medically attended AEs, and serious AEs were collected through end of study. Immunogenicity was assessed at baseline and months 1, 2, 3, and 6 following injection.RESULTSTwenty-five adults of Japanese descent aged ≥60 years received one injection of mRNA-1345 100 μg (n = 21) or placebo (n = 4). mRNA-1345 was well-tolerated; the most common local and systemic solicited ARs were injection site pain, and fatigue and myalgia, respectively, which were generally mild to moderate and transient. No serious AEs were reported. Neutralizing (nAb) and binding (bAb) antibodies were detectable at baseline, consistent with prior RSV exposure. mRNA-1345 boosted RSV nAb titers and preF bAb concentrations 1 month post-injection (geometric mean fold rise: RSV-A nAb, 11.2; RSV-B nAb, 6.6; preF bAb, 9.1). Titers among mRNA-1345 recipients remained above baseline through 6 months.CONCLUSIONSmRNA-1345 100 μg was well-tolerated among older adults of Japanese descent and induced nAbs and bAbs which were durable through 6 months, supporting its continued development.TRIAL REGISTRATIONClinicalTrials.gov, NCT04528719.

2024-09-01·World Allergy Organization Journal

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update – XI – Milk supplement/replacement formulas for infants and toddlers with CMA – Systematic review

Article

作者: Dahdah, Lamia ; Brożek, Jan L. ; Warner, Amena ; Kamenwa, Rose ; Terracciano, Luigi ; Papadopoulos, Nikolaos G ; Dupont, Christophe ; Horvath, Andrea ; Shamir, Raanan ; Pawankar, Ruby ; Arasi, Stefania ; Ansotegui, Ignacio J ; Galli, Elena ; Schünemann, Holger J ; Wong, Gary Wing Kin ; Nowak-Wegrzyn, Anna H. ; Mihara, Hanako ; Papadopoulos, Nikolaos G. ; Szajewska, Hania ; Said, Maria ; Bahna, Sami ; Li, Haiqi ; Fiocchi, Alessandro ; Dziechciarz, Piotr ; Waffenschmidt, Siw ; Bognanni, Antonio ; Martelli, Alberto ; Roldan, Yetiani ; Brożek, Jan L ; Firmino, Ramon T. ; Assa'Ad, Amal ; Agarwal, Arnav ; Chu, Derek K ; Firmino, Ramon T ; Lack, Gideon ; Starok, Anna ; Chu, Alexandro W L ; Bozzola, Martin ; Chu, Derek K. ; Waserman, Susan ; Vandenplas, Yvan ; Ebisawa, Motohiro ; Chu, Alexandro W.L. ; Ansotegui, Ignacio J. ; Schünemann, Holger J. ; Venter, Carina ; Nowak-Wegrzyn, Anna H ; Spergel, Jonathan

BackgroundCow's milk allergy (CMA) is the most complex and common food allergy in infants. Elimination of cow's milk from the diet and replacement with a specialized formula for infants with cow's milk allergy who cannot be breastfed is an established approach to minimize the risk of severe allergic reactions while avoiding nutritional deficiencies. Given the availability of multiple options, such as extensively hydrolyzed cow's milk-based formula (eHF-CM), aminoacid formula (AAF), hydrolyzed rice formula (HRF), and soy formula (SF), there is some uncertainty regarding which formula might represent the most suitable choice with respect to health outcomes. The addition of probiotics to a specialized formula has also been proposed as a potential approach to possibly increase the benefit. We systematically reviewed specialized formulas for infants with CMA to inform the updated World Allergy Organization (WAO) DRACMA guidelines.ObjectiveTo systematically review and synthesize the available evidence about the use of specialized formulas for the management of individuals with CMA.MethodsWe searched from inception PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and the websites of selected allergy organizations, for randomized and non-randomized trials of any language investigating specialized formulas with or without probiotics. We included all studies irrespective of the language of the original publication. The last search was conducted in January 2024. We synthesized the identified evidence quantitatively or narratively as appropriate and summarized it in the evidence profiles. We conducted this review following the PRISMA, Cochrane methods, and the GRADE approach.ResultsWe identified 3558 records including 14 randomized trials and 7 observational studies. Very low certainty evidence suggested that in infants with IgE-mediated CMA, eHF-CM, compared with AAF, might have higher probability of outgrowing CMA (risk ratio (RR) 2.32; risk difference (RD) 25 more per 100), while showing potentially lower probability of severe vomiting (RR 0.12, 95% CI 0.02 to 0.88; RD 23 fewer per 100, 95% CI 3 to 26) and developing food protein-induced enterocolitis syndrome (FPIES) (RR 0.15, 95% CI 0.03 to 0.82; RD 34 fewer per 100, 95% CI 7 to 39). We also found, however, that eHF-CM might be inferior to AAF in supporting a physiological growth, with respect to both weight (-5.5% from baseline, 95%CI -9.5% to -1.5%) and length (-0.7 z-score change, 95%CI -1.15 to -0.25) (very low certainty). We found similar effects for eHF-CM, compared with AAF, also in non-IgE CMA. When compared with SF, eHF-CM might favor weight gain for IgE CMA infants (0.23 z-score change, 95%CI 0.01 to 0.45), and tolerance acquisition (RR 1.86, 95%CI 1.03 to 3.37; RD 27%, 95%CI 1%-74%) for non-IgE CMA (both at very low certainty of the evidence (CoE)). The comparison of eHF-CM vs. HRF, and HRF vs. SF, showed no difference in effect (very low certainty). For IgE CMA patients, low certainty evidence suggested that adding probiotics (L. rhamnosus GG, L. casei CRL431 and B. lactis Bb-12) might increase the probability of developing CMA tolerance (RR 2.47, 95%CI 1.03 to 5.93; RD 27%, 95%CI 1%-91%), and reduce the risk of severe wheezing (RR 0.12, 95%CI 0.02 to 0.95; RD -23%, 95%CI -8% to -0.4%). However, in non-IgE CMA infants, the addition of probiotics (L. rhamnosus GG) showed no significant effect, as supported by low to very low CoE.ConclusionsCurrently available studies comparing eHF-CM, AAF, HRF, and SF provide very low certainty evidence about their effects in infants with IgE-mediated and non-IgE-mediated CMA. Our review revealed several limitations in the current body of evidence, primarily arising from concerns related to the quality of studies, the limited size of the participant populations and most importantly the lack of diversity and standardization in the compared interventions. It is therefore imperative for future studies to be methodologically rigorous and investigate a broader spectrum of available interventions. We encourage clinicians and researchers to review current World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines for suggestions on how to use milk replacement formulas in clinical practice and what additional research would be the most beneficial.

Igaku to Yakugaku

HIV preventive vaccines: expectations for mRNA vaccines

作者: Leav, Brett ; Himansu, Sunny ; Mihara, Hanako

A review.Vaccines to prevent human immunodeficiency virus type 1 (HIV-1) infection remain a major unmet need.Although the development of vaccines to prevent HIV-1 infection has been considered extremely difficult, recent advances in mRNA (mRNA) vaccine platform technol. have led to the development of effective vaccines to prevent HIV-1 infection.It is expected to be a useful tool for the future.In this review, we discuss key results obtained from HIV vaccine trials designed to date, efforts to develop mRNA-based vaccines, and new strategies for preventing HIV-1 by inducing broadly neutralizing antibodies.

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100 项与 Moderna Japan Co. Ltd. 相关的转化医学

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