In-utero exposure to maternal HIV infection alters T-cell immune responses to vaccination in HIV-uninfected infants.
OBJECTIVE
In sub-Saharan Africa, HIV-exposed uninfected (HEU) infants have higher morbidity and mortality than HIV-unexposed infants. To evaluate whether immune dysfunction contributes to this vulnerability of HEU infants, we conducted a longitudinal, observational cohort study to assess T-cell immune responses to infant vaccines (Mycobacterium bovis BCG and acellular pertussis) and staphylococcal enterotoxin B (SEB). In total, 46 HEU and 46 HIV-unexposed infants were recruited from Khayelitsha, Cape Town.


METHODS
Vaccine-specific T-cell proliferation (Ki67 expression) and intracellular expression of four cytokines [interferon-γ, interleukin (IL)-2, IL-13 and IL-17] were measured after whole blood stimulation with antigens at 6 and 14 weeks of age.


RESULTS
HEU infants demonstrated elevated BCG-specific CD4 and CD8 T-cell proliferative responses at 14 weeks (P  = 0.041 and 0.002, respectively). These responses were significantly increased even after adjusting for birth weight, feeding mode and gestational age. Similar to BCG, increased CD4 and CD8 T-cell proliferation was evident in response to SEB stimulation (P  = 0.004 and 0.002, respectively), although pertussis-specific T cells proliferated comparably between the two groups. Within HEU infants, maternal CD4 cell count and length of antenatal antiretroviral exposure had no effect on T-cell proliferation to BCG or SEB. HIV exposure significantly diminished measurable cytokine polyfunctionality in response to BCG, Bordetella pertussis and SEB stimulation.


CONCLUSIONS
These data show for the first time, when adjusting for confounders, that exposure to HIV in utero is associated with significant alterations to CD4 and CD8T-cell immune responses in infants to vaccines and nonspecific antigens.
aDivision of Immunology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town bDesmond Tutu TB Centre, Faculty of Medicine and Health Sciences, Stellenbosch University, Parow cDivision of Virology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town dNational Health Laboratory Services, South Africa eDivision of Epidemiology & Biostatistics, School of Public Health & Family Medicine, University of Cape Town, Cape Town, South Africa fSeattle Biomedical Research Institute, Seattle, Washington, USA.
Elvis B
EB
Kidzeru
Anneke C
AC
Hesseling
Jo-Ann S
JA
Passmore
Landon
L
Myer
Hoyam
H
Gamieldien
Christophe Toukam
CT
Tchakoute
Clive M
CM
Gray
Donald L
DL
Sodora
Heather B
HB
Jaspan
D017954:Africa South of the Sahara; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D049109:Cell Proliferation; D015331:Cohort Studies; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019394:Ki-67 Antigen / Q000032:analysis; D008137:Longitudinal Studies; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D010567:Pertussis Vaccine / Q000008:administration & dosage / Q000276:immunology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology*; D013209:Staphylococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D022282:Vaccines, Acellular / Q000008:administration & dosage / Q000276:immunology
D001500:BCG Vaccine; D016207:Cytokines; D019394:Ki-67 Antigen; D010567:Pertussis Vaccine; D013209:Staphylococcal Vaccines; D022282:Vaccines, Acellular