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Exome Sequencing Reveals a Rare Autosomal Dominant Variant in MSTO1 Gene as a Novel Leber’s Hereditary Optic Neuropathy (LHON) Modifier in a Thai Family with High Penetrance of G11778A Mutation
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Document Title
Exome Sequencing Reveals a Rare Autosomal Dominant Variant in MSTO1 Gene as a Novel Leber's Hereditary Optic Neuropathy (LHON) Modifier in a Thai Family with High Penetrance of G11778A Mutation
Author
Nakhonsri V., Kaewsutthi S., Suktitipat B., Suthammarak W., Chuenkongkaew W.L., Wasitthankasem R., Tongsima S., Lertrit P.
Affiliations
Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Phaholpolpayuhasena Hospital, Kanchanaburi, Thailand; Center of Excellence for Biomedical and Public Health Informatics (BIOPHICS), Bangkok, Thailand; Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Faculty of Medicine, Thammasat University (Rangsit Campus), Pathum Thani, Thailand; National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani, Thailand; Faculty of Tropical Medicine, Hospital for Tropical Diseases, Bangkok, Thailand; Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand; International Vaccine Institute, Seoul, South Korea; Janssen Global Medical Affairs, Beerse, Belgium; Janssen Asia Pacific Medical Affairs Operations, Sydney, Australia; Centre of Regulatory Excellence, Duke-NUS Medical School, Singapore; Vaccine and Infectious Disease Organization, University of Saskatchewan, Canada
Type
Article
Source Title
Vaccine
ISSN
0264410X
Year
2024
Open Access
All Open Access, Hybrid Gold
Publisher
Elsevier Ltd
DOI
10.1016/j.vaccine.2024.05.010
Abstract
Background: Inactivated whole-virus vaccination elicits immune responses to both SARS-CoV-2 nucleocapsid (N) and spike (S) proteins, like natural infections. A heterologous Ad26.COV2.S booster given at two different intervals after primary BBIBP-CorV vaccination was safe and immunogenic at days 28 and 84, with higher immune responses observed after the longer pre-boost interval. We describe booster-specific and hybrid immune responses over 1 year. Methods: This open-label phase 1/2 study was conducted in healthy Thai adults aged ? 18 years who had completed primary BBIBP-CorV primary vaccination between 90–240 (Arm A1; n = 361) or 45–75 days (Arm A2; n = 104) before enrolment. All received an Ad26.COV2.S booster. We measured anti-S and anti-N IgG antibodies by Elecsys?, neutralizing antibodies by SARS-CoV-2 pseudovirus neutralization assay, and T-cell responses by quantitative interferon (IFN)-? release assay. Immune responses were evaluated in the baseline-seronegative population (pre-booster anti-N < 1.4 U/mL; n = 241) that included the booster-effect subgroup (anti-N < 1.4 U/mL at each visit) and the hybrid-immunity subgroup (anti-N ? 1.4 U/mL and/or SARS-CoV-2 infection, irrespective of receiving non-study COVID-19 boosters). Results: In Arm A1 of the booster-effect subgroup, anti-S GMCs were 131-fold higher than baseline at day 336; neutralizing responses against ancestral SARS-CoV-2 were 5-fold higher than baseline at day 168; 4-fold against Omicron BA.2 at day 84. IFN-? remained approximately 4-fold higher than baseline at days 168 and 336 in 18–59-year-olds. Booster-specific responses trended lower in Arm A2. In the hybrid-immunity subgroup at day 336, anti-S GMCs in A1 were 517-fold higher than baseline; neutralizing responses against ancestral SARS-CoV-2 and Omicron BA.2 were 28- and 31-fold higher, respectively, and IFN-? was approximately 14-fold higher in 18–59-year-olds at day 336. Durable immune responses trended lower in ? 60-year-olds. Conclusion: A heterologous Ad26.COV2.S booster after primary BBIBP-CorV vaccination induced booster-specific immune responses detectable up to 1 year that were higher in participants with hybrid immunity. Clinical Trials Registration. NCT05109559. ? 2024
License
CC BY-NC
Rights
Authors
Publication Source
WoS