Low CD4+ T-Cell Levels and B-Cell Apoptosis in Vertically HIV-exposed Noninfected Children and Adolescents

Miyamoto, Maristela; Pessoa, Silvana Duarte; Ono, Érika; Machado, Daisy Maria; Salomão, Reinaldo; Succi, Regina Célia de Menezes; Pahwa, Savita; Moraes-Pinto, Maria Isabel de

doi:10.1093/tropej/fmq024

Cited by 34 publications

(32 citation statements)

References 25 publications

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“…The diminished baseline prevaccine antibody levels for tetanus (significant) and Hib (not significant) we detected in HEU infants could be due to lower levels of vaccine-specific antibodies in the mother, placental dysfunction resulting in decreased antibody transfer, or decreased half-life of transferred maternal antibodies (21,22,24,32). On the other hand, the higher levels of prevaccine HepB antibodies observed in HEU infants likely reflected maternal HepB infection in HIV-infected mothers; indeed, high variability in the prevaccine HepB antibody levels were observed in our HEU cohort, suggesting that individual differences, such as maternal HepB infection, are involved.…”

Section: Discussionmentioning

confidence: 89%

Antibody Responses to Vaccination among South African HIV-Exposed and Unexposed Uninfected Infants during the First 2 Years of Life

Reikie

Naidoo

Ruck

et al. 2013

Clin Vaccine Immunol

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e HIV-exposed but uninfected (HEU) infants born to HIV-infected mothers from areas in the world with a high burden of infectious disease suffer higher infectious morbidity and mortality than their HIV unexposed uninfected (HUU) peers. Vaccination provides protection from infection. The possibility exists that altered response to vaccination contributes to the higher rate of infection in HEU than in HUU infants. While short-term, cross-sectional studies support this notion, it is unclear whether or not HEU infants develop long-term protective immune responses following the WHO extended program on immunization (EPI).Vaccine-specific antibody responses were compared between HEU and HUU infants from 2 weeks until 2 years of age in a longitudinal South African cohort. Total IgG and antibodies specific for Bordetella pertussis, Haemophilus influenzae type b (Hib), tetanus toxoid, hepatitis B virus (HepB), and measles virus were measured at multiple time points throughout the first 2 years of life. Prevaccine antibodies (maternal antibodies passively acquired) specific for tetanus were lower in HEU than in HUU infants, while prevaccine antibodies to HepB were higher in HEU than in HUU infants. Both groups responded similarly to tetanus, Hib, and HepB vaccination. HEU demonstrated stronger pertussis vaccine responses, developing protective titers 1 year earlier than HUU patients, and maintained higher anti-tetanus titers at 24 months of age. Vaccine-induced antibodies to measles virus were similar in both groups at all time points. Our results suggest that the current EPI vaccination program as practiced in South Africa leads to the development of vaccine-specific antibody responses that are equivalent in HEU and HUU infants. However, our data also suggest that a large fraction of both HEU and HUU South African infants have antibody titers for several infectious threats that remain below the level of protection for much of their first 2 years of life.

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Section: Discussionmentioning

confidence: 89%

Antibody Responses to Vaccination among South African HIV-Exposed and Unexposed Uninfected Infants during the First 2 Years of Life

Reikie

Naidoo

Ruck

et al. 2013

Clin Vaccine Immunol

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“…Mortality in this population is higher than in infants of uninfected mothers, and these children are at increased risk of pneumonia and diarrhea, which may relate in part to altered immune maturation and function in HEU infants compared with those in unexposed infants of HIV-uninfected mothers (7)(8)(9)(10)(11). Such potential immune impairment may also compromise responses to primary vaccination in the first year of life and lead to specific susceptibility to vaccine-preventable illnesses, including Hib (12).…”

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confidence: 99%

Impaired Haemophilus influenzae Type b Transplacental Antibody Transmission and Declining Antibody Avidity through the First Year of Life Represent Potential Vulnerabilities for HIV-Exposed but -Uninfected Infants

Gaensbauer

Rakhola

Onyango‐Makumbi

et al. 2014

Clin. Vaccine Immunol.

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fTo determine whether immune function is impaired among HIV-exposed but -uninfected (HEU) infants born to HIV-infected mothers and to identify potential vulnerabilities to vaccine-preventable infection, we characterized the mother-to-infant placental transfer of Haemophilus influenzae type b-specific IgG (Hib-IgG) and its levels and avidity after vaccination in Ugandan HEU infants and in HIV-unexposed U.S. infants. Hib-IgG was measured by enzyme-linked immunosorbent assay in 57 Ugandan HIVinfected mothers prenatally and in their vaccinated HEU infants and 14 HIV-unexposed U.S. infants at birth and 12, 24, and 48 weeks of age. Antibody avidity at birth and 48 weeks of age was determined with 1 M ammonium thiocyanate. A median of 43% of maternal Hib-IgG was transferred to HEU infants. Although its level was lower in HEU infants than in U.S. infants at birth (P < 0.001), Hib-IgG was present at protective levels (>1.0 g/ml) at birth in 90% of HEU infants and all U.S. infants. HEU infants had robust Hib-IgG responses to a primary vaccination. Although Hib-IgG levels declined from 24 to 48 weeks of age in HEU infants, they were higher than those in U.S. infants (P ‫؍‬ 0.002). Antibody avidity, comparable at birth, declined by 48 weeks of age in both populations. Early vaccination of HEU infants may limit an initial vulnerability to Hib disease resulting from impaired transplacental antibody transfer. While initial Hib vaccine responses appeared adequate, the confluence of lower antibody avidity and declining Hib-IgG levels in HEU infants by 12 months support Hib booster vaccination at 1 year. Potential immunologic impairments of HEU infants should be considered in the development of vaccine platforms for populations with high maternal HIV prevalence.

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“…Also, the antiretroviral (ARV) prophylaxis of vertical transmission can act on the placental environment, causing changes in cytokine expression (9). The newborns present abnormalities in mitochondrial function (2), in hematological features (5,10,17), and in the maturation of T and B lymphocytes (3,4,8,11,12,20,24,25).…”

mentioning

confidence: 99%

Impaired Humoral Response to Vaccines among HIV-Exposed Uninfected Infants

Abramczuk

Mazzola

Moreno

et al. 2011

Clin. Vaccine Immunol.

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Little is known about the vaccine protective response for infants born from HIV-infected mothers. We evaluated the antibody response to hepatitis B, tetanus, and diphtheria vaccine in vertically HIV-exposed uninfected infants and compared them to those of control infants not exposed to the virus. The quantitative determination of specific neutralizing antibodies against hepatitis B, diphtheria, and tetanus were performed blindly on serum samples. The results showed that 6.7% of the HIV-exposed uninfected individuals were nonresponders to hepatitis B vaccine (anti-HBs titer, <10 mIU/ml), and 64.4% were very good responders (anti-HBs titer, >1,000 mIU/ml), whereas only 3.6% of the nonexposed infants were nonresponders ( 2 ‫؍‬ 10.93; 1 df). The HIV-exposed uninfected infants showed protective titers for diphtheria and tetanus but lower geometric mean anti-tetanus titers compared to those of the HIV-unexposed infants. Our data point to the necessity of evaluating vaccine immune responses in these children and reinforced that alterations in lymphocyte numbers and functions reported for newborns from HIV-infected mothers interfere with the vaccine response.

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Low CD4+ T-Cell Levels and B-Cell Apoptosis in Vertically HIV-exposed Noninfected Children and Adolescents

Cited by 34 publications

References 25 publications

Antibody Responses to Vaccination among South African HIV-Exposed and Unexposed Uninfected Infants during the First 2 Years of Life

Antibody Responses to Vaccination among South African HIV-Exposed and Unexposed Uninfected Infants during the First 2 Years of Life

Impaired Haemophilus influenzae Type b Transplacental Antibody Transmission and Declining Antibody Avidity through the First Year of Life Represent Potential Vulnerabilities for HIV-Exposed but -Uninfected Infants

Impaired Humoral Response to Vaccines among HIV-Exposed Uninfected Infants

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