Infant HIV type 1 gp120 vaccination elicits robust and durable anti-V1V2 immunoglobulin G responses and only rare envelope-specific immunoglobulin a responses

Genevieve G. Fouda*, Coleen K. Cunningham, Elizabeth J. McFarland, William Borkowsky, Petronella Muresan, Justin Pollara, Lin Ye Song, Brooke E. Liebl, Kaylan Whitaker, Xiaoying Shen, Nathan A. Vandergrift, R. Glenn Overman, Nicole L. Yates, M. Anthony Moody, Carrie Fry, Jerome H. Kim, Nelson L. Michael, Merlin Robb, Punnee Pitisuttithum, Jaranit KaewkungwalSorachai Nitayaphan, Supachai Rerks-Ngarm, Hua Xin Liao, Barton F. Haynes, David C. Montefiori, Guido Ferrari, Georgia D. Tomaras, Sallie R. Permar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Background Infant responses to vaccines can be impeded by maternal antibodies and immune system immaturity. It is therefore unclear whether human immunodeficiency virus type 1 (HIV-1) vaccination would elicit similar responses in adults and infants. Method HIV-1 Env-specific antibody responses were evaluated in 2 completed pediatric vaccine trials. In the Pediatric AIDS Clinical Trials Group (PACTG) 230 protocol, infants were vaccinated with 4 doses of Chiron rgp120 with MF59 (n = 48), VaxGen rgp120 with aluminum hydroxide (alum; n = 49), or placebo (n = 19) between 0 and 20 weeks of age. In PACTG 326, infants received 4 doses of ALVAC-HIV-1/AIDSVAX B/B with alum (n = 9) or placebo (n = 13) between 0 and 12 weeks of age. Results By 52 weeks of age, the majority of maternally acquired antibodies had waned and vaccine Env-specific immunoglobulin G (IgG) responses in vaccinees were higher than in placebo recipients. Chiron vaccine recipients had higher and more-durable IgG responses than VaxGen vaccine recipients or ALVAC/AIDSVAX vaccinees, with vaccine-elicited IgG responses still detectable in 56% of recipients at 2 years of age. Remarkably, at peak immunogenicity, the concentration of anti-V1V2 IgG, a response associated with a reduced risk of HIV-1 acquisition in the RV144 adult vaccine trial, was 22-fold higher in Chiron vaccine recipients, compared with RV144 vaccinees. Conclusion As exemplified by the Chiron vaccine regimen, vaccination of infants against HIV-1 can induce robust, durable Env-specific IgG responses, including anti-V1V2 IgG.

Original languageEnglish
Pages (from-to)508-517
Number of pages10
JournalJournal of Infectious Diseases
Volume211
Issue number4
DOIs
StatePublished - 15 Feb 2015
Externally publishedYes

Keywords

  • HIV-1
  • antibodies
  • infants
  • vaccine

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