BACKGROUND: Recent studies have indicated that broadly neutralizing antibodies (bnAbs) in children may develop earlier after human immunodeficiency virus (HIV) infection compared to adults. METHODS: We evaluated plasma from 212 antiretroviral therapy-naive children with HIV (1-3 years old). Neutralization breadth and potency was assessed using a panel of 10 viruses and compared to adults with chronic HIV. The magnitude, epitope specificity, and immunoglobulin (Ig)G subclass distribution of Env-specific antibodies were assessed using a binding antibody multiplex assay. RESULTS: One-year-old children demonstrated neutralization breadth comparable to chronically infected adults, whereas 2- and 3-year-olds exhibited significantly greater neutralization breadth (P = .014). Likewise, binding antibody responses increased with age, with levels in 2- and 3-year-old children comparable to adults. Overall, there was no significant difference in antibody specificities or IgG subclass distribution between the pediatric and adult cohorts. It is interesting to note that the neutralization activity was mapped to a single epitope (CD4 binding site, V2 or V3 glycans) in only 5 of 38 pediatric broadly neutralizing samples, which suggests that most children may develop a polyclonal neutralization response. CONCLUSIONS: These results contribute to a growing body of evidence suggesting that initiating HIV immunization early in life may present advantages for the development of broadly neutralizing antibody responses.
BACKGROUND: Recent studies have indicated that broadly neutralizing antibodies (bnAbs) in children may develop earlier after human immunodeficiency virus (HIV) infection compared to adults. METHODS: We evaluated plasma from 212 antiretroviral therapy-naive children with HIV (1-3 years old). Neutralization breadth and potency was assessed using a panel of 10 viruses and compared to adults with chronic HIV. The magnitude, epitope specificity, and immunoglobulin (Ig)G subclass distribution of Env-specific antibodies were assessed using a binding antibody multiplex assay. RESULTS: One-year-old children demonstrated neutralization breadth comparable to chronically infected adults, whereas 2- and 3-year-olds exhibited significantly greater neutralization breadth (P = .014). Likewise, binding antibody responses increased with age, with levels in 2- and 3-year-old children comparable to adults. Overall, there was no significant difference in antibody specificities or IgG subclass distribution between the pediatric and adult cohorts. It is interesting to note that the neutralization activity was mapped to a single epitope (CD4 binding site, V2 or V3 glycans) in only 5 of 38 pediatric broadly neutralizing samples, which suggests that most children may develop a polyclonal neutralization response. CONCLUSIONS: These results contribute to a growing body of evidence suggesting that initiating HIV immunization early in life may present advantages for the development of broadly neutralizing antibody responses.
Authors: Bonnie Phillips; Genevieve G Fouda; Josh Eudailey; Justin Pollara; Alan D Curtis; Erika Kunz; Maria Dennis; Xiaoying Shen; Camden Bay; Michael Hudgens; David Pickup; S Munir Alam; Amir Ardeshir; Pamela A Kozlowski; Koen K A Van Rompay; Guido Ferrari; M Anthony Moody; Sallie Permar; Kristina De Paris Journal: Clin Vaccine Immunol Date: 2017-10-05
Authors: Georgia D Tomaras; James M Binley; Elin S Gray; Emma T Crooks; Keiko Osawa; Penny L Moore; Nancy Tumba; Tommy Tong; Xiaoying Shen; Nicole L Yates; Julie Decker; Constantinos Kurt Wibmer; Feng Gao; S Munir Alam; Philippa Easterbrook; Salim Abdool Karim; Gift Kamanga; John A Crump; Myron Cohen; George M Shaw; John R Mascola; Barton F Haynes; David C Montefiori; Lynn Morris Journal: J Virol Date: 2011-08-17 Impact factor: 5.103
Authors: S E Starr; C V Fletcher; S A Spector; F H Yong; T Fenton; R C Brundage; D Manion; N Ruiz; M Gersten; M Becker; J McNamara; L M Mofenson; L Purdue; S Siminski; B Graham; D M Kornhauser; W Fiske; C Vincent; H W Lischner; W M Dankner; P M Flynn Journal: N Engl J Med Date: 1999-12-16 Impact factor: 91.245
Authors: Laura M Walker; Melissa D Simek; Frances Priddy; Johannes S Gach; Denise Wagner; Michael B Zwick; Sanjay K Phogat; Pascal Poignard; Dennis R Burton Journal: PLoS Pathog Date: 2010-08-05 Impact factor: 6.823
Authors: Maximilian Muenchhoff; Emily Adland; Owen Karimanzira; Carol Crowther; Matthew Pace; Anna Csala; Ellen Leitman; Angeline Moonsamy; Callum McGregor; Jacob Hurst; Andreas Groll; Masahiko Mori; Smruti Sinmyee; Christina Thobakgale; Gareth Tudor-Williams; Andrew J Prendergast; Henrik Kloverpris; Julia Roider; Alasdair Leslie; Delane Shingadia; Thea Brits; Samantha Daniels; John Frater; Christian B Willberg; Bruce D Walker; Thumbi Ndung'u; Pieter Jooste; Penny L Moore; Lynn Morris; Philip Goulder Journal: Sci Transl Med Date: 2016-09-28 Impact factor: 17.956