Postnatal Zika virus infection of nonhuman primate infants born to mothers infected with homologous Brazilian Zika virus.

Recent data in a nonhuman primate model showed that infants postnatally infected with Zika virus (ZIKV) were acutely susceptible to high viremia and neurological damage, suggesting the window of vulnerability extends beyond gestation. In this pilot study, we addressed the susceptibility of two infant rhesus macaques born healthy to dams infected with Zika virus during pregnancy. Passively acquired neutralizing antibody titers dropped below detection limits between 2 and 3 months of age, while binding antibodies remained detectable until viral infection at 5 months. Acute serum viremia was comparatively lower than adults infected with the same Brazilian isolate of ZIKV (n = 11 pregnant females, 4 males, and 4 non-pregnant females). Virus was never detected in cerebrospinal fluid nor in neural tissues at necropsy two weeks after infection. However, viral RNA was detected in lymph nodes, confirming some tissue dissemination. Though protection was not absolute and our study lacks an important comparison with postnatally infected infants born to naïve dams, our data suggest infants born healthy to infected mothers may harbor a modest but important level of protection from postnatally acquired ZIKV for several months after birth, an encouraging result given the potentially severe infection outcomes of this population.

Efficient transplacental IgG transfer in women infected with Zika virus during pregnancy.

Zika virus (ZIKV) is a newly-identified infectious cause of congenital disease. Transplacental transfer of maternal IgG to the fetus plays an important role in preventing many neonatal infections. However, antibody transfer may also have negative consequences, such as mediating enhancement of flavivirus infections in early life, or trafficking of virus immune complexes to the fetal compartment. ZIKV infection produces placental pathology which could lead to impaired IgG transfer efficiency as occurs in other maternal infections, such as HIV-1 and malaria. In this study, we asked whether ZIKV infection during pregnancy impairs transplacental transfer of IgG. We enrolled pregnant women with fever or rash in a prospective cohort in Vitoria, Brazil during the recent ZIKV epidemic. ZIKV and dengue virus (DENV)-specific IgG, ZIKV and DENV neutralizing antibodies, and routine vaccine antigen-specific IgG were measured in maternal samples collected around delivery and 20 paired cord blood samples. We concluded that 8 of these mothers were infected with ZIKV during pregnancy and 12 were ZIKV-uninfected. The magnitude of flavivirus-specific IgG, neutralizing antibody, and vaccine-elicited IgG were highly correlated between maternal plasma and infant cord blood in both ZIKV-infected and -uninfected mother-infant pairs. Moreover, there was no difference in the magnitude of plasma flavivirus-specific IgG levels between mothers and infants regardless of ZIKV infection status. Our data suggests that maternal ZIKV infection during pregnancy does not impair the efficiency of placental transfer of flavivirus-specific, functional, and vaccine-elicited IgG. These findings have implications for the neonatal outomes of maternal ZIKV infection and optimal administration of antibody-based ZIKV vaccines and therapeutics.

Mercury Exposure and Poor Nutritional Status Reduce Response to Six Expanded Program on Immunization Vaccines in Children: An Observational Cohort Study of Communities Affected by Gold Mining in the Peruvian Amazon.

Background: Poor nutritional status combined with mercury exposure can generate adverse child health outcomes. Diet is a mediator of mercury exposure and evidence suggests that nutritional status modifies aspects of mercury toxicity. However, health impacts beyond the nervous system are poorly understood. This study evaluates antibody responses to six vaccines from the expanded program on immunization (EPI), including hepatitis B, Haemophilus influenzae type B, measles, pertussis, tetanus, and diphtheria in children with variable hair mercury and malnutrition indicators. Methods: An observational cohort study (n = 98) was conducted in native and non-native communities in Madre de Dios, Peru, a region with elevated mercury exposure from artisanal and small-scale gold mining. Adaptive immune responses in young (3⁻48 months) and older children (4⁻8 year olds) were evaluated by vaccine type (live attenuated, protein subunits, toxoids) to account for differences in response by antigen, and measured by total IgG concentration and antibody (IgG) concentrations of each EPI vaccine. Mercury was measured from hair samples and malnutrition determined using anthropometry and hemoglobin levels in blood. Generalized linear mixed models were used to evaluate associations with each antibody type. Results: Changes in child antibodies and protection levels were associated with malnutrition indicators, mercury exposure, and their interaction. Malnutrition was associated with decreased measles and diphtheria-specific IgG. A one-unit decrease in hemoglobin was associated with a 0.17 IU/mL (95% CI: 0.04⁻0.30) decline in measles-specific IgG in younger children and 2.56 (95% CI: 1.01⁻6.25) higher odds of being unprotected against diphtheria in older children. Associations between mercury exposure and immune responses were also dependent on child age. In younger children, one-unit increase in log10 child hair mercury content was associated with 0.68 IU/mL (95% CI: 0.18⁻1.17) higher pertussis and 0.79 IU/mL (95% CI: 0.18⁻1.70) higher diphtheria-specific IgG levels. In older children, child hair mercury content exceeding 1.2 µg/g was associated with 73.7 higher odds (95% CI: 2.7⁻1984.3) of being a non-responder against measles and hair mercury content exceeding 2.0 µg/g with 0.32 IU/mL (95% CI: 0.10⁻0.69) lower measles-specific antibodies. Log10 hair mercury significantly interacted with weight-for-height z-score, indicating a multiplicative effect of higher mercury and lower nutrition on measles response. Specifically, among older children with poor nutrition (WHZ = -1), log10 measles antibody is reduced from 1.40 to 0.43 for low (<1.2 µg/g) vs. high mercury exposure, whereas for children with good nutritional status (WHZ = 1), log10 measles antibody is minimally changed for low vs. high mercury exposure (0.72 vs. 0.81, respectively). Conclusions: Child immune response to EPI vaccines may be attenuated in regions with elevated mercury exposure risk and exacerbated by concurrent malnutrition.

Innate Immune Factors in Mothers' Breast Milk and Their Lack of Association With Rotavirus Vaccine Immunogenicity in Nicaraguan Infants.

To better understand underlying causes of lower rotavirus vaccine effectiveness in low-middle income countries (LMICs), we measured innate antiviral factors in Nicaraguan mothers' milk and immune response to the first dose of the pentavalent rotavirus vaccine in corresponding infants. No relationship was found between concentrations of innate factors and rotavirus vaccine response.