Infectivity and Immunogenicity of Live-Attenuated Respiratory Syncytial Virus Vaccines in Human Immunodeficiency Virus-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 Jr; Ruth A Karron; Peter L Collins; Ursula J Buchholz; International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1114, 2000, 2011, 2012, 2013, and 2018 Study Teams

doi:10.1093/ofid/ofae679

Infectivity and Immunogenicity of Live-Attenuated Respiratory Syncytial Virus Vaccines in Human Immunodeficiency Virus-Exposed Uninfected Children

Open Forum Infect Dis. 2024 Nov 13;11(12):ofae679. doi: 10.1093/ofid/ofae679. eCollection 2024 Dec.

Authors

Collaborators

International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1114, 2000, 2011, 2012, 2013, and 2018 Study Teams:
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 Cielo

Affiliations

¹ Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, USA.
² Department of Pediatrics, University of California Irvine School of Medicine, Orange, California, USA.
³ Department of Medicine, Children's Hospital of Orange County, Orange, California, USA.
⁴ Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children's Hospital Colorado, Aurora, Colorado, USA.
⁵ Center for Biostatistics in AIDS Research, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA.
⁶ FHI 360, Durham, North Carolina, USA.
⁷ FHI 360, Washington, District of Columbia, USA.
⁸ Maternal, Adolescent and Pediatric Research Branch, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
⁹ Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
¹⁰ Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
¹¹ Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

Abstract

Background: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory illness among young children. Human immunodeficiency virus (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 7 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 immunoglobulin G (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.

Keywords: antibody interference; live-attenuated RSV vaccine; maternal HIV infection; transplacental antibody transfer; vaccine-elicited immunogenicity.