Different adjuvanted pediatric HIV envelope vaccines induced distinct plasma antibody responses despite similar B cell receptor repertoires in infant rhesus macaques

Different HIV vaccine regimens elicit distinct plasma antibody responses in both human and nonhuman primate models. Previous studies in human and non-human primate infants showed that adjuvants influenced the quality of plasma antibody responses induced by pediatric HIV envelope vaccine regimens. We recently reported that use of the 3M052-SE adjuvant and longer intervals between vaccinations are associated with higher magnitude of antibody responses in infant rhesus macaques. However, the impact of different adjuvants in HIV vaccine regimens on the developing infant B cell receptor (BCR) repertoire has not been studied. This study evaluated whether pediatric HIV envelope vaccine regimens with different adjuvants induced distinct antigen-specific memory B cell repertoires and whether specific immunoglobulin (Ig) immunogenetic characteristics are associated with higher magnitude of plasma antibody responses in vaccinated infant rhesus macaques. We utilized archived preclinical pediatric HIV vaccine studies PBMCs and tissue samples from 19 infant rhesus macaques immunized either with (i) HIV Env protein with a squalene adjuvant, (ii) MVA-HIV and Env protein co-administered using a 3-week interval, (iii) MVA-HIV prime/ protein boost with an extended 6-week interval between immunizations, or (iv) with HIV Env administered with 3M-052-SE adjuvant. Frequencies of vaccine-elicited HIV Env-specific memory B cells from PBMCs and tissues were similar across vaccination groups (frequency range of 0.06–1.72%). There was no association between vaccine-elicited antigen-specific memory B cell frequencies and plasma antibody titer or avidity. Moreover, the epitope specificity and Ig immunogenetic features of vaccine-elicited monoclonal antibodies did not differ between the different vaccine regimens. These data suggest that pediatric HIV envelope vaccine candidates with different adjuvants that previously induced higher magnitude and quality of plasma antibody responses in infant rhesus macaques were not driven by distinct antigen-specific memory BCR repertoires.

Immune Dysregulation Is Associated with Neurodevelopment and Neurocognitive Performance in HIV Pediatric Populations—A Scoping Review

HIV-1 is known for its complex interaction with the dysregulated immune system and is responsible for the development of neurocognitive deficits and neurodevelopmental delays in pediatric HIV populations. Considering that HIV-1-induced immune dysregulation and its association with neurodevelopmental and neurocognitive impairments in pediatric populations are not well understood, we conducted a scoping review on this topic. The study aimed to systematically review the association of blood and cerebrospinal fluid (CSF) immune markers with neurocognitive deficits and neurodevelopmental delays in pediatric HIV populations. PubMed, Scopus, and Web of Science databases were searched using a search protocol designed specifically for this study. Studies were selected based on a set eligibility criterion. Titles, abstracts, and full texts were assessed by two independent reviewers. Data from the selected studies were extracted and analyzed by two independent reviewers. Seven studies were considered eligible for use in this context, which included four cross-sectional and three longitudinal studies. An average of 130 (±70.61) children living with HIV, 138 (±65.37) children exposed to HIV but uninfected and 90 (±86.66) HIV-negative participants were included across the seven studies. Results indicate that blood and CSF immune markers are associated with neurocognitive development/performance in pediatric HIV populations. Only seven studies met the inclusion criteria, therefore, these limited the number of significant conclusions which could have been made by using such an approach. All considered, the evidence suggests that immune dysregulation, as in the case of adult HIV populations, also has a significant association with neurocognitive performance in pediatric HIV populations.

Cytomegalovirus pneumonia of infants in Africa: a narrative literature review

Cytomegalovirus pneumonia has repeatedly been described in the context of HIV-exposed uninfected and HIV-infected infants. Despite its significant role in the etiology of childhood pneumonia, there is still a paucity of literature generally, and specifically in Africa, suggesting that it might be a neglected disease. Emerging evidence highlights the importance of postnatal transmission through breastmilk. The pathogenetic significance of the multiplicity of strains acquired through repeated re-infections in early infancy is unknown. The development of cheap, accurate diagnostic tools and safe, effective antivirals and the maintenance of effective prevention and treatment of pediatric HIV are needed to manage cytomegalovirus pneumonia in low-resource settings.

A clinico epidemiological study of pediatric dermatoses of HIV infected children in a tertiary care hospital of North Bengal

Background: Pediatric Human immunodeficiency virus (HIV) infection and its dermatological manifestation has emerged a serious burden globally including India. Dermatological manifestations are unique in pediatric HIV infection and related to CD4 cell count and its percentage. The study was carried out to assess the cutaneous manifestation of HIV positive pediatric patients and its correlation with CD4 cell count in eastern part of India below 12 years of age.Methods: This analytic epidemiological study with prospective observational design was carried among 30 HIV positive children below 12 years of age in our institution over a period of one year.Results: Total 30 HIV infected children were studied among male 23 (76.67%)) and female 7 (23.33%). Age ranged from birth to 12 years with mean was 6.39±2.48 years. The skin lesions are highest in 3-6 yrs age group 12 (40%) and 33.33% of them had CD4 counts between 500-750 while 3.33% had CD4 counts above 1500. 27 patients (90%) were received ART and 3 (10%) patients were without ART. Nine distinct patterns of lesions: abscess (3), furuncles (1), maculopapular rash (2), papular (7), pruritic (10), plaque (3), soreness of tongue (2), pustules (1) and red scaly (1) were detected. 46.67% pain (14), 40.0% itching (12) and 13.33% burning sensation (4) were the main symptoms and 20.0% face (6), 16.7% oral cavity (5), 20.0% hands (6), 10.0% abdomen (3) and 33.3% legs (10) were principal site of involvement. 13 different skin lesions: fungal infection (3), furuncles (1), urticaria (4), scabies (5), prurigo (5), measles (1), molluscum contagiosum (1), abscess (3), venous leg (1), pyoderma (1), atopic dermatitis (1), chicken pox (2) and glossitis (2) were diagnosed.Conclusions: Various dermatological manifestations are common with pediatric HIV infection and sometime are the first clinical presentation that is well correlated with CD4 cell count and its percentage.