Defective monocyte enzymatic function and an inhibitory immune phenotype in HIV-exposed uninfected African infants in the era of antiretroviral therapy

Louise Afran; Kondwani Jambo; Wilfred Nedi; David J.C. Miles; Anmol Kiran; Dominic H. Banda; Ralph Kamg'Ona; Dumizulu Tembo; Annette Pachnio; Eleni Nastouli; Brigit Ferne; Henry Mwandumba; Paul Moss; David Goldblatt; Sarah Rowland-Jones; Adam Finn; Robert S. Heyderman

doi:10.1093/infdis/jiac133

Defective monocyte enzymatic function and an inhibitory immune phenotype in HIV-exposed uninfected African infants in the era of antiretroviral therapy

Louise Afran, Kondwani Jambo, Wilfred Nedi, David J.C. Miles, Anmol Kiran, Dominic H. Banda, Ralph Kamg'Ona, Dumizulu Tembo, Annette Pachnio, Eleni Nastouli, Brigit Ferne, Henry Mwandumba, Paul Moss, David Goldblatt, Sarah Rowland-Jones, Adam Finn, Robert S. Heyderman

Clinical Sciences

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

Background

HIV-Exposed Uninfected (HEU) infants are a rapidly expanding population in sub-Saharan Africa, highly susceptible to encapsulated bacterial disease in the first year of life. The mechanism of this increased risk is still poorly understood. We investigated if HIV-exposure dysregulates HEU immunity, vaccine-antibody production and human herpes virus (HHV) amplify this effect.

Methods

34 HIV-infected and 44 HIV-uninfected pregnant women were recruited into the birth cohort, followed up to 6 weeks of age; and 43 HIV-infected and 61 HIV-uninfected mother-infant pairs into a longitudinal infant cohort, at either: 5-7 to 14-15; or 14-15 to 18-23 weeks of age. We compared monocyte function, innate and adaptive immune cell phenotype, and vaccine-induced antibody responses between HEU and HU infants.

Results

We demonstrate altered monocyte phagosomal function and B cell subset homeostasis, and lower vaccine-induced anti-Haemophilus influenzae type b (Hib) and anti-Tetanus Toxoid (TT) IgG titers in HEU compared to HU infants. HHV infection was similar between HEU and HU infants.

Conclusion

In the era of antiretroviral therapy (ART)-mediated viral suppression, HIV-exposure may dysregulate monocyte and B cell function, during the vulnerable period of immune maturation. This may contribute to the high rates of invasive bacterial disease and pneumonia in HEU infants.

Original language	English
Pages (from-to)	1243-1255
Number of pages	13
Journal	Journal of Infectious Diseases
Volume	226
Issue number	7
Early online date	11 Apr 2022
DOIs	https://doi.org/10.1093/infdis/jiac133
Publication status	E-pub ahead of print - 11 Apr 2022

Keywords

Heamophilus influenzae type b
HIV-exposed uninfected
human herpes virus'
monocytes
vaccine responses

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/infdis/jiac133Licence: CC BY

Jiac133Final published version, 1.04 MBLicence: CC BY

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Afran, L., Jambo, K., Nedi, W., Miles, D. J. C., Kiran, A., Banda, D. H., Kamg'Ona, R., Tembo, D., Pachnio, A., Nastouli, E., Ferne, B., Mwandumba, H., Moss, P., Goldblatt, D., Rowland-Jones, S., Finn, A., & Heyderman, R. S. (2022). Defective monocyte enzymatic function and an inhibitory immune phenotype in HIV-exposed uninfected African infants in the era of antiretroviral therapy. Journal of Infectious Diseases, 226(7), 1243-1255. Advance online publication. https://doi.org/10.1093/infdis/jiac133

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title = "Defective monocyte enzymatic function and an inhibitory immune phenotype in HIV-exposed uninfected African infants in the era of antiretroviral therapy",

abstract = "Background HIV-Exposed Uninfected (HEU) infants are a rapidly expanding population in sub-Saharan Africa, highly susceptible to encapsulated bacterial disease in the first year of life. The mechanism of this increased risk is still poorly understood. We investigated if HIV-exposure dysregulates HEU immunity, vaccine-antibody production and human herpes virus (HHV) amplify this effect. Methods 34 HIV-infected and 44 HIV-uninfected pregnant women were recruited into the birth cohort, followed up to 6 weeks of age; and 43 HIV-infected and 61 HIV-uninfected mother-infant pairs into a longitudinal infant cohort, at either: 5-7 to 14-15; or 14-15 to 18-23 weeks of age. We compared monocyte function, innate and adaptive immune cell phenotype, and vaccine-induced antibody responses between HEU and HU infants. Results We demonstrate altered monocyte phagosomal function and B cell subset homeostasis, and lower vaccine-induced anti-Haemophilus influenzae type b (Hib) and anti-Tetanus Toxoid (TT) IgG titers in HEU compared to HU infants. HHV infection was similar between HEU and HU infants. Conclusion In the era of antiretroviral therapy (ART)-mediated viral suppression, HIV-exposure may dysregulate monocyte and B cell function, during the vulnerable period of immune maturation. This may contribute to the high rates of invasive bacterial disease and pneumonia in HEU infants.",

keywords = "Heamophilus influenzae type b, HIV-exposed uninfected, human herpes virus', monocytes, vaccine responses",

author = "Louise Afran and Kondwani Jambo and Wilfred Nedi and Miles, \{David J.C.\} and Anmol Kiran and Banda, \{Dominic H.\} and Ralph Kamg'Ona and Dumizulu Tembo and Annette Pachnio and Eleni Nastouli and Brigit Ferne and Henry Mwandumba and Paul Moss and David Goldblatt and Sarah Rowland-Jones and Adam Finn and Heyderman, \{Robert S.\}",

year = "2022",

month = apr,

day = "11",

doi = "10.1093/infdis/jiac133",

language = "English",

volume = "226",

pages = "1243--1255",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

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Afran, L, Jambo, K, Nedi, W, Miles, DJC, Kiran, A, Banda, DH, Kamg'Ona, R, Tembo, D, Pachnio, A, Nastouli, E, Ferne, B, Mwandumba, H, Moss, P, Goldblatt, D, Rowland-Jones, S, Finn, A & Heyderman, RS 2022, 'Defective monocyte enzymatic function and an inhibitory immune phenotype in HIV-exposed uninfected African infants in the era of antiretroviral therapy', Journal of Infectious Diseases, vol. 226, no. 7, pp. 1243-1255. https://doi.org/10.1093/infdis/jiac133

TY - JOUR

T1 - Defective monocyte enzymatic function and an inhibitory immune phenotype in HIV-exposed uninfected African infants in the era of antiretroviral therapy

AU - Afran, Louise

AU - Jambo, Kondwani

AU - Nedi, Wilfred

AU - Miles, David J.C.

AU - Kiran, Anmol

AU - Banda, Dominic H.

AU - Kamg'Ona, Ralph

AU - Tembo, Dumizulu

AU - Pachnio, Annette

AU - Nastouli, Eleni

AU - Ferne, Brigit

AU - Mwandumba, Henry

AU - Moss, Paul

AU - Goldblatt, David

AU - Rowland-Jones, Sarah

AU - Finn, Adam

AU - Heyderman, Robert S.

PY - 2022/4/11

Y1 - 2022/4/11

N2 - Background HIV-Exposed Uninfected (HEU) infants are a rapidly expanding population in sub-Saharan Africa, highly susceptible to encapsulated bacterial disease in the first year of life. The mechanism of this increased risk is still poorly understood. We investigated if HIV-exposure dysregulates HEU immunity, vaccine-antibody production and human herpes virus (HHV) amplify this effect. Methods 34 HIV-infected and 44 HIV-uninfected pregnant women were recruited into the birth cohort, followed up to 6 weeks of age; and 43 HIV-infected and 61 HIV-uninfected mother-infant pairs into a longitudinal infant cohort, at either: 5-7 to 14-15; or 14-15 to 18-23 weeks of age. We compared monocyte function, innate and adaptive immune cell phenotype, and vaccine-induced antibody responses between HEU and HU infants. Results We demonstrate altered monocyte phagosomal function and B cell subset homeostasis, and lower vaccine-induced anti-Haemophilus influenzae type b (Hib) and anti-Tetanus Toxoid (TT) IgG titers in HEU compared to HU infants. HHV infection was similar between HEU and HU infants. Conclusion In the era of antiretroviral therapy (ART)-mediated viral suppression, HIV-exposure may dysregulate monocyte and B cell function, during the vulnerable period of immune maturation. This may contribute to the high rates of invasive bacterial disease and pneumonia in HEU infants.

AB - Background HIV-Exposed Uninfected (HEU) infants are a rapidly expanding population in sub-Saharan Africa, highly susceptible to encapsulated bacterial disease in the first year of life. The mechanism of this increased risk is still poorly understood. We investigated if HIV-exposure dysregulates HEU immunity, vaccine-antibody production and human herpes virus (HHV) amplify this effect. Methods 34 HIV-infected and 44 HIV-uninfected pregnant women were recruited into the birth cohort, followed up to 6 weeks of age; and 43 HIV-infected and 61 HIV-uninfected mother-infant pairs into a longitudinal infant cohort, at either: 5-7 to 14-15; or 14-15 to 18-23 weeks of age. We compared monocyte function, innate and adaptive immune cell phenotype, and vaccine-induced antibody responses between HEU and HU infants. Results We demonstrate altered monocyte phagosomal function and B cell subset homeostasis, and lower vaccine-induced anti-Haemophilus influenzae type b (Hib) and anti-Tetanus Toxoid (TT) IgG titers in HEU compared to HU infants. HHV infection was similar between HEU and HU infants. Conclusion In the era of antiretroviral therapy (ART)-mediated viral suppression, HIV-exposure may dysregulate monocyte and B cell function, during the vulnerable period of immune maturation. This may contribute to the high rates of invasive bacterial disease and pneumonia in HEU infants.

KW - Heamophilus influenzae type b

KW - HIV-exposed uninfected

KW - human herpes virus'

KW - monocytes

KW - vaccine responses

U2 - 10.1093/infdis/jiac133

DO - 10.1093/infdis/jiac133

M3 - Article

SN - 0022-1899

VL - 226

SP - 1243

EP - 1255

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 7

ER -

Defective monocyte enzymatic function and an inhibitory immune phenotype in HIV-exposed uninfected African infants in the era of antiretroviral therapy

Abstract

Keywords

UN SDGs

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