Jessica E Atwell1, Bhagvanji Thumar1, Maria A Formica2, Leanne J Robinson2,3, Edward E Walsh2, Christopher L King4, Ruth A Karron1. 1. From the Department of International, Center for Immunization Research, Health Johns Hopkins School of Public Health, Baltimore, Maryland. 2. Department of Medicine, Rochester General Hospital, University of Rochester, New York, New York. 3. Burnet Institute, Victoria, Australia. 4. Center for Global Health and Disease, Veterans Affairs Medical Center, Case Western Reserve University, Cleveland, Ohio.
Abstract
BACKGROUND: Passively-acquired respiratory syncytial virus (RSV) neutralizing antibody (Ab) can protect against RSV-associated lower respiratory tract illness. Maternal RSV immunization is, therefore, an attractive strategy for protection of very young infants. Vaccines for this purpose are currently being evaluated in clinical trials, but conditions such as preterm birth, placental malaria, maternal hypergammaglobulinemia and HIV infection might threaten this strategy. Each has been shown to impair transplacental Ab transfer for a variety of pathogens, but RSV-specific data are limited. Work in The Gambia demonstrated that placental malaria impaired transplacental transfer of RSV Ab, but a subsequent study in malaria-endemic Papua New Guinea (PNG) indicated that such associations may have been confounded by hypergammaglobulinemia (IgG > 1700 mg/dL). METHODS: Here we confirm and extend those findings by measuring RSV neutralizing Ab and maternal IgG in sera from a larger cohort of 325 mother/infant pairs in PNG, and demonstrate the applicability of a high-throughput assay for assessment of neutralizing Ab. RESULTS: One-third of mother-infant pairs demonstrated impaired RSV Ab transfer. Infants of hypergammaglobulinemic women were more likely to have both impaired transfer [cord-to-maternal titer ratio <1.0, adjusted odds ratio (OR): 3.36 (95% confidence interval: 1.81-6.30)] and the lowest RSV cord titers [adjusted OR: 5.09 (95% confidence interval: 1.95-13.32, P < 0.001)], but neither outcome was associated with placental malaria. CONCLUSIONS: Once maternal RSV vaccines become available, successful implementation will require clear understanding and mitigation of factors that can impair passive protection, necessitating epidemiologic studies of such relationships ahead of vaccine availability. This study underscores the need to focus on hypergammaglobulinemia as a condition of importance.
BACKGROUND: Passively-acquired respiratory syncytial virus (RSV) neutralizing antibody (Ab) can protect against RSV-associated lower respiratory tract illness. Maternal RSV immunization is, therefore, an attractive strategy for protection of very young infants. Vaccines for this purpose are currently being evaluated in clinical trials, but conditions such as preterm birth, placental malaria, maternal hypergammaglobulinemia and HIV infection might threaten this strategy. Each has been shown to impair transplacental Ab transfer for a variety of pathogens, but RSV-specific data are limited. Work in The Gambia demonstrated that placental malaria impaired transplacental transfer of RSV Ab, but a subsequent study in malaria-endemic Papua New Guinea (PNG) indicated that such associations may have been confounded by hypergammaglobulinemia (IgG > 1700 mg/dL). METHODS: Here we confirm and extend those findings by measuring RSV neutralizing Ab and maternal IgG in sera from a larger cohort of 325 mother/infant pairs in PNG, and demonstrate the applicability of a high-throughput assay for assessment of neutralizing Ab. RESULTS: One-third of mother-infant pairs demonstrated impaired RSV Ab transfer. Infants of hypergammaglobulinemicwomen were more likely to have both impaired transfer [cord-to-maternal titer ratio <1.0, adjusted odds ratio (OR): 3.36 (95% confidence interval: 1.81-6.30)] and the lowest RSV cord titers [adjusted OR: 5.09 (95% confidence interval: 1.95-13.32, P < 0.001)], but neither outcome was associated with placental malaria. CONCLUSIONS: Once maternal RSV vaccines become available, successful implementation will require clear understanding and mitigation of factors that can impair passive protection, necessitating epidemiologic studies of such relationships ahead of vaccine availability. This study underscores the need to focus on hypergammaglobulinemia as a condition of importance.
Authors: Sepideh Dolatshahi; Audrey L Butler; Mark J Siedner; Joseph Ngonzi; Andrea G Edlow; Julian Adong; Madeleine F Jennewein; Caroline Atyeo; Ingrid V Bassett; Drucilla J Roberts; Douglas A Lauffenburger; Galit Alter; Lisa M Bebell Journal: Clin Infect Dis Date: 2022-10-12 Impact factor: 20.999
Authors: Joyce U Nyiro; Elizabeth Bukusi; Dufton Mwaengo; Amek Nyaguara; Bryan Nyawanda; Nancy Otieno; Godfrey Bigogo; Nickson Murunga; Marc-Alain Widdowson; Jennifer R Verani; Sandra S Chaves; Hope Mwangudza; Calleb Odundo; James A Berkley; D James Nokes; Patrick K Munywoki Journal: Wellcome Open Res Date: 2022-04-01