Background: HIV-exposed uninfected infants have increased infection risk and mortality compared to HIV-unexposed infants. HIV-exposed infants may be at increased risk of invasive GBS disease due to reduced maternal antibody against GBS. Methods: We quantified antibodies that bind to the surface of whole Group B Streptococcus (GBS) of serotypes Ia, Ib, II, III and V using novel flow cytometry assays in South African HIV-infected and non-infected mothers and their uninfected infants. Antibody-mediated complement C3b/iC3b deposition onto GBS of these serotypes was also quantified by a novel flow cytometry assay. Results: Geometric mean concentration (GMC) of both surface-binding anti-GBS antibody and antibody-mediated complement deposition onto GBS were reduced in HIV-infected women (n= 46) compared to HIV-uninfected women (n= 58) for ST1a (surface-binding: 19.3 vs 29.3; p= 0.003; complement deposition: 2.9 vs 5.3. SU/mL; p= 0.003), STIb (24.9 vs 47.6; p= 0.003; 2.6 vs 4.9. SU/mL; p= 0.003), STII (19.8 vs 50.0; p= 0.001; 3.1 vs 6.2. SU/mL; p= 0.001), STIII (27.8 vs 60.1; p= 0.001; 2.8 vs 5.3. SU/mL; p= 0.001) and STV (121.9 vs 185.6. SU/mL; p<. 0.001) and in their infants for STIa (complement deposition 9.4 vs 27.0. SU/mL; p= 0.02), STIb (13.4 vs 24.5. SU/mL; p= 0.02), STII (14.6 vs 42.7. SU/mL; p= 0.03), STIII (26.6 vs 62.7. SU/mL; p= 0.03) and STV (90.4 vs 165.8. SU/mL; p= 0.04). Median transplacental transfer of antibody from HIV-infected women to their infants was reduced compared to HIV-uninfected women for GBS serotypes II (0.42 [IQR 0.22-0.59] vs 1.0. SU/mL [0.42-1.66]; p<. 0.001), III (0.54 [0.31-1.03] vs 0.95. SU/mL [0.42-3.05], p= 0.05) and V (0.51 [0.28-0.79] vs 0.75. SU/mL [0.26-2.9], p= 0.04). The differences between infants remained significant at 16 weeks of age. Conclusions: Maternal HIV infection was associated with lower anti-GBS surface binding antibody concentration and antibody-mediated C3b/iC3b deposition onto GBS bacteria of serotypes Ia, Ib, II, III and V. This may render these infants more susceptible to early and late onset GBS disease.
Bibliographical noteFunding Information:
Conflict of interest statement: PTH is an investigator for research studies done on behalf of St Georges, University of London (London, UK) and funded by Novartis vaccines (Siena, Italy) and serves as a consultant to Novartis vaccines on GBS vaccines. KLD is funded by a Wellcome Trust Global Health Fellowship (London, UK), Royal College of Physicians Thomas Watt Eden Fellowship (London, UK) and BHIVA/Gilead Registrar Award (London, UK). BK is funded by an MRC Program grant (London, UK) and an NIHR Senior Research fellowship (London, UK). CJ was funded by ESPID (Geneva, Switzerland) and The Thrasher Research Fund (Atlanta, USA). Funding: This work is supported by a Wellcome Trust Global Health Fellowship (Grant Number KLD2013 ); The Thomas Watt Eden Fellowship (Royal College of Physicians Grant Number 01012013 ); and the Gilead/BHIVA Registrar Award. Contribution statement: KLD developed the manuscript and original research idea. LA participated in the research. PTH, BK, ST, CJ developed the original idea and substantially contributed to the development of the manuscript.
- Group B Streptococcus
- HIV-exposed-uninfected infants