Dataset Information

Longitudinal quantification of adenovirus neutralizing responses in Zambian mother-infant pairs: Impact of HIV-1 infection and its treatment.

ABSTRACT: Vaccination offers the most cost-effective approach to limiting the adverse impact of infectious and neoplastic diseases that reduce the quality of life in sub-Saharan Africa (SSA). However, it is unclear what vaccine vectors would be most readily implementable in the setting and at what age they should be applied for maximal efficacy. Adenoviruses (Ad) and Ad-based vectors have been demonstrated to induce effective humoral and cellular immune responses in animal models and in humans. However, because immunity associated with Ad infection is lifelong, there exists a debate as to whether pre-existing immunity might decrease the efficacy of Ad vectored vaccines. In order to begin to rationally develop vaccination strategies for SSA, we have quantified neutralizing antibodies (nAb) against Ad4, Ad5, Ad7, Ad26, Ad28, Ad45 and Ad48 in 67 adult women and their infants. We are the first to define the decay kinetics of transferred maternal nAb in infants as well as the apparent initiation of de novo Ad responses. Our findings demonstrate that in Zambian adults, robust nAb responses exist against each of the Ads tested and are efficiently transferred to newborns. With few exceptions, neither the HIV-1 infection status of the mothers or the antiretroviral therapy (ART) treatment of HIV-1 disease had significant impact on maternal Ad nAb responses or their transfer to infants. However, maternal Ad nAb decays in infants to a nadir at 12?months of age such that any of the seven Ad types could function as vaccine vectors. The definition of this 'window of opportunity' provides important foundational data for rational design and implementation of Ad vectors in this setting.

SUBMITTER: Privatt SR

PROVIDER: S-EPMC7182153 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Longitudinal quantification of adenovirus neutralizing responses in Zambian mother-infant pairs: Impact of HIV-1 infection and its treatment.

Privatt Sara R SR Bullard Brianna L BL Weaver Eric A EA Wood Charles C West John T JT

Vaccine 20190801 36

Vaccination offers the most cost-effective approach to limiting the adverse impact of infectious and neoplastic diseases that reduce the quality of life in sub-Saharan Africa (SSA). However, it is unclear what vaccine vectors would be most readily implementable in the setting and at what age they should be applied for maximal efficacy. Adenoviruses (Ad) and Ad-based vectors have been demonstrated to induce effective humoral and cellular immune responses in animal models and in humans. However, b ...[more]

PMID: 31378535

Similar Datasets

Project description:Background Maternal vaccination with tetanus, reduced-dose diphtheria, and acellular pertussis vaccine (Tdap) could be an effective way of mitigating the high residual burden of infant morbidity and mortality caused by Bordetella pertussis To better inform such interventions, we conducted a burden-of-disease study to determine the incidence of severe and nonsevere pertussis among a population of Zambian infants.Methods Mother-infant pairs were enrolled at 1 week of life, and then seen at 2- to 3-week intervals through 14 weeks of age. At each visit, nasopharyngeal (NP) swabs were obtained from both, and symptoms were catalogued. Using polymerase chain reaction (PCR) to identify cases, and a severity scoring system to triage these into severe/nonsevere, we calculated disease incidence using person-time at risk as the denominator.Results From a population of 1981 infants, we identified 10 with clinical pertussis, for an overall incidence of 2.4 cases (95% confidence interval [CI], 1.2-4.2) per 1000 infant-months and a cumulative incidence of 5.2 cases (95% CI, 2.6-9.0) per 1000 infants. Nine of 10 cases occurred within a 3-month window (May-July 2015), with highest incidence between birth and 6 weeks of age (3.5 cases per 1000 infant-months), concentrated among infants prior to vaccination or among those who had only received 1 dose of Diphtheria Tetanus whole cell Pertussis (DTwP). Maternal human immunodeficiency virus (HIV) modestly increased the risk of infant pertussis (risk ratio, 1.8 [95% CI, .5-6.9]). Only 1 of 10 infant cases qualified as having severe pertussis. The rest presented with the mild and nonspecific symptoms of cough, coryza, and/or tachypnea. Notably, cough durations were long, exceeding 30 days in several cases, with PCRs repeatedly positive over time.Conclusions Pertussis is circulating freely among this population of Zambian infants but rarely presents with the classical symptoms of paroxysmal cough, whooping, apnea, and cyanosis. Maternal HIV appears to increase the risk, while lack of effective exposure to DTwP increased the risk.

Project description:BackgroundRetention along the elimination of Mother to Child Transmission (eMTCT) cascade in Uganda remains poor as only 62.7%-69.5% are followed up to 18months. The objective of this study was to determine the rates of retention of mother-baby pairs at two levels of the eMTCT cascade (12 and 18 months) and associated factors.MethodsThis was a longitudinal analysis of 368 mother-baby pairs who were enrolled into the eMTCT program in Kaberamaido district from January 2013 to December 2018. Data was extracted from early infant diagnosis (EID) and mothers' ART registers, entered into Microsoft Excel and then exported to Stata statistical software package version 14.0 for management and analysis. Descriptive statistics such as mean and frequencies were computed at univariate level. At the bivariate level, Cox proportional hazard regression was performed to assess the level of association between the primary outcome and each independent variable, while Cox proportional hazard regression model was built at multivariate level to determine the factors independently associated with retention of mother-baby pairs in the eMTCT program.ResultsOf the 368 mothers enrolled into the study, their average age was 29.7years (SD = 6.6). Nearly two-thirds of the mothers were married/cohabiting, (n = 232, 63.0%). The 368 mother baby pairs were observed for a total time of 6340 person months, with majority, 349 (94.8%, 95%CI = 92.0-96.7) still active in eMTCT care, while 19(5.2%, 95%CI = 3.3-8.0) were lost to follow up at 12months. At 18 months, 323 (87.8%, 95%CI = 84.0-90.8) were active in eMTCT program while 45(12.2%, 95 CI = 9.2-16.0) were lost to follow up. At bivariate level, marital status, health facility level of enrolment, mothers' ART treatment supporter, and mothers' ART enrolment time were significantly associated with survival/lost to follow up (LTFU) of mother-baby pairs along the eMTCT cascade. At multivariable level, the mothers' time of ART initiation was significantly associated with survival/lost to follow up (LTFU) of mother-baby pairs at along the eMTCT cascade, with mothers-baby pairs who were initiated during the antenatal/post-natal periods having higher hazards of LTFU compared to those who initiated ART before Antenatal period (before pregnancy), aHR = 4.37(95%CI, 1.62-11.76, P = 0.003). Mother-baby pairs who were enrolled into the eMTCT program after the implementation of HIV test and treat policy (year 2017 and 2018) had higher hazards of LTFU as compared to those enrolled before the implementation of test and treat policy in Uganda (year 2013-2016), aHR = 2.22(95% CI, 1.15-4.30, P = 0.017). All the other factors had no significant association with lost to follow up and cascade completion at multivariate level.ConclusionThere was high level of retention of mother-baby pairs in the eMTCT program in Kaberamaido at 12 months, but it was suboptimal at 18months. ART initiation during the antenatal and/or post-natal period was significantly associated with suboptimal retention of mother-baby pairs along the eMTCT cascade.

Project description:BACKGROUND:Bifidobacteria are important probiotics; some of the beneficial effects of bifidobacteria are achieved by the hydrolysis of glycans in the human gut. However, because the diet of breastfed infants typically lacks plant-derived glycans, in the gut environment of mothers and their breastfed infants, the mother will intake a variety of plant-derived glycans, such as from onions and bananas, through her diet. Under this assumption, we are interested in whether the same species of bifidobacteria isolated from mother-infant pairs present a distinction in their hydrolysis of plant-derived carbohydrates. RESULTS:Among the 36 Bifidobacterium strains, bifidobacterial carbohydrate utilization showed two trends related to the intestinal environment where the bacteria lived. Compared with infant-type bifidobacterial strains, adult-type bifidobacterial strains preferred to use plant-derived glycans. Of these strains, 10 isolates, 2 Bifidobacterium pseudocatenulatum (B. pseudocatenulatum), 2 Bifidobacterium pseudolongum (B. pseudolongum), 2 Bifidobacterium bifidum (B. bifidum), 2 Bifidobacterium breve (B. breve), and 2 Bifidobacterium longum (B. longum), were shared between the mother-infant pairs. Moreover, the repetitive sequence-based polymerase chain reaction (rep-PCR) results illustrated that B. pseudolongum and B. bifidum showed genotypic similarities of 95.3 and 98.2%, respectively. Combined with the carbohydrate fermentation study, these results indicated that the adult-type strains have a stronger ability to use plant-derived glycans than infant-type strains. Our work suggests that bifidobacterial carbohydrate metabolism differences resulted in the selective adaptation to the distinct intestinal environment of an adult or breastfed infant. CONCLUSIONS:The present study revealed that the different gut environments can lead to the differences in the polysaccharide utilization in the same strains of bifidobacterial strains, suggesting a further goal of investigating the exact expression of certain enzymes in response to specific carbon sources.

Dataset Information

Longitudinal quantification of adenovirus neutralizing responses in Zambian mother-infant pairs: Impact of HIV-1 infection and its treatment.

Publications

Longitudinal quantification of adenovirus neutralizing responses in Zambian mother-infant pairs: Impact of HIV-1 infection and its treatment.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets