Association between maternal stress and premature milk cortisol, milk IgA, and infant health: a cohort study.

Background: Maternal stress is pervasive in the neonatal intensive care unit (NICU). Maternal stress is associated with changes in human milk (HM) immunomodulatory agents, which may impact neonatal health. We sought to determine the association between maternal stress, HM immunoglobulin A (IgA) and cortisol, and to assess how these milk components correlate with infant immune and neurodevelopmental outcomes. We then compared how these associations persist over time. Methods: The study design involved a cohort study of exclusively breastfeeding mothers and their singleton moderately preterm (28-34 weeks) infants admitted to the NICU. We collected maternal serum, maternal saliva, and first-morning whole milk samples, and administered maternal stress questionnaires at 1 and 5 weeks postpartum. We analyzed the samples for HM IgA (using a customized immunoassay in skim milk) and for HM and salivary cortisol (using a chemiluminescent immunoassay). Infant illness was assessed using the Score for Neonatal Acute Physiology II (SNAP II) and SNAP II with Perinatal Extension (SNAPPE II), and infant neurodevelopment were assessed using the Test of Infant Motor Performance. We analyzed changes in HM IgA and cortisol over time using paired t-tests. Furthermore, we performed correlation and regression analyses after adjusting for gestational age (GA), corrected GA, and infant days of life. Results: In our study, we enrolled 26 dyads, with a mean maternal age of 28.1 years, consisting of 69% white, 19% Black, and 8% Hispanic. Cortisol: Salivary and HM cortisol were closely associated in week 1 but not in week 5. Though mean salivary cortisol remained stable over time [2.41 ng/mL (SD 2.43) to 2.32 (SD 1.77), p = 0.17], mean HM cortisol increased [1.96 ng/mL (SD 1.93) to 5.93 ng/mL (SD 3.83), p < 0.001]. Stress measures were inversely associated with HM cortisol at week 1 but not at week 5. IgA: HM IgA decreased over time (mean = -0.14 mg/mL, SD 0.53, p < 0.0001). High maternal stress, as measured by the Parental Stressor Scale: neonatal intensive care unit (PSS:NICU), was positively associated with HM IgA at week 5 (r = 0.79, P ≤ 0.001). Higher IgA was associated with a lower (better) SNAP II score at week 1 (r = -0.74, p = 0.05). No associations were found between maternal stress, salivary cortisol, HM cortisol, or HM IgA and neurodevelopment at discharge (as assessed using the TIMP score). Furthermore, these relationships did not differ by infant sex. Conclusion: Maternal stress showed associations with HM cortisol and HM IgA. In turn, HM IgA was associated with lower measures of infant illness.

Novel malaria antigen Plasmodium yoelii E140 induces antibody-mediated sterile protection in mice against malaria challenge.

Only a small fraction of the antigens expressed by malaria parasites have been evaluated as vaccine candidates. A successful malaria subunit vaccine will likely require multiple antigenic targets to achieve broad protection with high protective efficacy. Here we describe protective efficacy of a novel antigen, Plasmodium yoelii (Py) E140 (PyE140), evaluated against P. yoelii challenge of mice. Vaccines targeting PyE140 reproducibly induced up to 100% sterile protection in both inbred and outbred murine challenge models. Although PyE140 immunization induced high frequency and multifunctional CD8+ T cell responses, as well as CD4+ T cell responses, protection was mediated by PyE140 antibodies acting against blood stage parasites. Protection in mice was long-lasting with up to 100% sterile protection at twelve weeks post-immunization and durable high titer anti-PyE140 antibodies. The E140 antigen is expressed in all Plasmodium species, is highly conserved in both P. falciparum lab-adapted strains and endemic circulating parasites, and is thus a promising lead vaccine candidate for future evaluation against human malaria parasite species.

New gorilla adenovirus vaccine vectors induce potent immune responses and protection in a mouse malaria model.

BACKGROUND: A DNA-human Ad5 (HuAd5) prime-boost malaria vaccine has been shown to protect volunteers against a controlled human malaria infection. The potency of this vaccine, however, appeared to be affected by the presence of pre-existing immunity against the HuAd5 vector. Since HuAd5 seroprevalence is very high in malaria-endemic areas of the world, HuAd5 may not be the most appropriate malaria vaccine vector. This report describes the evaluation of the seroprevalence, immunogenicity and efficacy of three newly identified gorilla adenoviruses, GC44, GC45 and GC46, as potential malaria vaccine vectors. RESULTS: The seroprevalence of GC44, GC45 and GC46 is very low, and the three vectors are not efficiently neutralized by human sera from Kenya and Ghana, two countries where malaria is endemic. In mice, a single administration of GC44, GC45 and GC46 vectors expressing a murine malaria gene, Plasmodium yoelii circumsporozoite protein (PyCSP), induced robust PyCSP-specific T cell and antibody responses that were at least as high as a comparable HuAd5-PyCSP vector. Efficacy studies in a murine malaria model indicated that a prime-boost regimen with DNA-PyCSP and GC-PyCSP vectors can protect mice against a malaria challenge. Moreover, these studies indicated that a DNA-GC46-PyCSP vaccine regimen was significantly more efficacious than a DNA-HuAd5-PyCSP regimen. CONCLUSION: These data suggest that these gorilla-based adenovectors have key performance characteristics for an effective malaria vaccine. The superior performance of GC46 over HuAd5 highlights its potential for clinical development.