Infectivity and immunogenicity of live-attenuated respiratory syncytial virus vaccines in HIV-exposed uninfected children
Matthew S Kelly, Coleen K Cunningham, Elizabeth J McFarland, Mark J Giganti, Jane C Lindsey, Charlotte Perlowski, Jennifer L Libous, Patrick Jean-Philippe, Jack Moye, Ruth A Karron, Peter L Collins, Ursula J Buchholz, , Ram Yogev, Ellen Chadwick, Ellen Cooper, Richard Rutstein, Paul Spearman, Andres Camacho-Gonzalez, Ruth Karron, Andrew Wiznia, Joanna Dobroszycki, Mariam Aziz, Nehali Patel, Sharon Nachman, William Shearer, Mary Paul, Jaime Deville, Stephen Spector, Elizabeth McFarland, Mikhaela CieloAbstract
Background
Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory illness among young children. HIV-exposed uninfected (HEU) children experience a higher burden of RSV disease and have immune abnormalities that may influence their responses to live-attenuated RSV vaccines.
Methods
In a pooled analysis of clinical trials of seven live-attenuated, intranasal RSV vaccines conducted by the IMPAACT Network among children 6 to <25 months of age with serum RSV-neutralizing titers of <1:40, the infectivity and immunogenicity of these vaccines were compared among HEU and HIV-unexposed uninfected (HUU) children. Nasal washes were collected during the first 28 days after vaccination. Serum RSV-neutralizing and anti-RSV F glycoprotein IgG antibodies were measured prior to and 56 days after vaccination, and before and after the following winter season.
Results
Of 156 children, 90 (58%) were HUU and 66 (42%) were HEU. Seventy-six (84%) HUU and 63 (95%) HEU participants were infected with vaccine (shed vaccine virus and/or had a ≥4-fold rise in serum RSV antibodies at 56 days after vaccination). HUU children had higher serum RSV-neutralizing and anti-RSV F IgG titers prior to vaccination. Compared to HEU children, lower percentages of HUU children had ≥4-fold rises in RSV-neutralizing (67% vs. 88%) and anti-RSV F IgG (70% vs. 89%) titers at 56 days after vaccination.
Conclusions
Live-attenuated RSV vaccines are highly immunogenic in HEU children. Given their increased burden of RSV disease and higher early-childhood mortality in some settings, HEU children should be prioritized for vaccination against RSV as these vaccines become available.