Perinatal depression affects 10-20% of women and is associated with poor outcomes for mother and child. Inflammation is associated with depression in non-pregnant adults. Perinatal depression and inflammation in pregnancy are independently associated with morbidities including obesity, gestational diabetes, preeclampsia, and preterm birth. The role of inflammation in perinatal depression has received little attention. We hypothesized an association between self-reported perinatal depressive symptoms and serum inflammatory biomarkers TNF-alpha, IL-6, IL-1beta, and CRP. 110 healthy gravidas were recruited in third trimester from an academic medical center, with a baseline study visit at a mean of 32.5 (SD +/- 1.8) weeks gestational age. Sixty-three participants completed the Edinburgh Postnatal Depression Scale (EPDS) and provided demographic information and serum samples upon enrollment and at 3 and 6 months postpartum. Serum inflammatory markers were quantified by multiplex array. Multiple linear mixed effects models were used to evaluate trends of biomarkers with the EPDS score in the third trimester of pregnancy and the postpartum period. Elevated serum TNF-alpha was associated with lower EPDS total score (beta = - 0.90, p = 0.046) after adjusting for demographics and medication use. In contrast, IL-6, CRP, and IL-1beta did not demonstrate statistically significant associations with depressive symptoms by the EPDS in either crude or adjusted models. Study findings showed no association or an inverse (TNF-alpha) association between inflammatory markers and perinatal depressive symptoms. Relevant literature evaluating a role for inflammation in depression in the unique context of pregnancy is both limited and inconsistent, and further exploration is merited.

In recent years, heterologous prime-boost vaccines have been demonstrated to be an effective strategy for generating protective immunity, consisting of both humoral and cell-mediated immune responses against a variety of pathogens including HIV-1. Previous reports of preclinical and clinical studies have shown the enhanced immunogenicity of viral vector or DNA vaccination followed by heterologous protein boost, compared to using either prime or boost components alone. With such approaches, the selection of an adjuvant for inclusion in the protein boost component is expected to impact the immunogenicity and safety of a vaccine. In this study, we examined in a mouse model the serum cytokine and chemokine profiles for several candidate adjuvants: QS-21, Al(OH)3, monophosphoryl lipid A (MPLA) and ISCOMATRIX adjuvant, in the context of a previously tested pentavalent HIV-1 Env DNA prime-protein boost formulation, DP6-001. Our data revealed that the candidate adjuvants in the context of the DP6-001 formulation are characterized by unique serum cytokine and chemokine profiles. Such information will provide valuable guidance in the selection of an adjuvant for future AIDS vaccine development, with the ultimate goal of enhancing immunogenicity while minimizing reactogenicity associated with the use of an adjuvant. More significantly, results reported here will add to the knowledge on how to include an adjuvant in the context of a heterologous prime-protein boost vaccination strategy in general.

OBJECTIVE: The objective of this study is to characterize the cytokine response among patients presenting with an influenza-like illness who are infected with the influenza virus, a bacterial pneumonia, or another viral infection. We hypothesize that there are differences in proinflammatory and anti-inflammatory cytokines in relation to cytokines associated with the humoral response during viral and bacterial respiratory infections. METHODS: We enrolled adults who presented to an urban academic emergency department during the 2008 to 2011 influenza seasons with symptoms of fever and a cough. Subjects had nasal aspirates tested by viral culture, and peripheral blood drawn to quantify cytokine concentrations. Cytokine concentrations were compared between groups using the Wilcoxon rank sum test, and receiver operating characteristic curves were calculated. RESULTS: A total of 80 patients were enrolled: 40 with influenza infection, 14 patients with a bacterial pneumonia as determined by infiltrate on chest x-ray, and 26 patients negative for influenza infection and infiltrate. There were differences between the bacterial pneumonia group, and all other viral infections grouped together with regard to interleukin (IL) 4 (2.66 vs 16.77 pg/mL, P < .001), IL-5 (20.57 vs 57.57 pg/mL, P = .006), IL-6 (403.06 vs 52.69 pg/mL, P < .001), granulocyte macrophage colony-stimulating factor (18.26 vs 66.80 pg/mL, P < .001), and interferon gamma (0.0 vs 830.36 pg/mL, P < .001). Interleukin 10 concentrations were elevated in patients with influenza (88.69 pg/mL) compared with all other groups combined (39.19 pg/mL; P = .003). CONCLUSION: Cytokines IL-4, IL-5, IL-6, granulocyte macrophage colony-stimulating factor, and interferon gamma may serve as distinct markers of bacterial infection in patients with an influenza-like illness, whereas IL-10 is uniquely elevated in influenza patients.

In recent years, heterologous prime-boost vaccination constructs have emerged as a promising strategy to generate broad and protective immunity against a variety of pathogens. The utility of DNA vaccination in priming the immune system, in particular, has improved the immunogenicity of vaccines against difficult pathogens such as HIV-1. In addition, many vaccine formulations include an adjuvant to augment immune responses. However, the mechanisms and profiles of many adjuvants remain largely unknown, particularly in the context of such combination immunization approaches. My thesis research studied the effects of several adjuvants, QS-21, aluminum hydroxide, MPL, and ISCOMATRIX™ adjuvant in the context of a previously described pentavalent HIV-1 Env DNA prime-protein boost vaccine, DP6-001. In a murine model, we quantified HIV antigen-specific humoral and T cell responses, as well as pro-inflammatory serum cytokine and chemokines, both shortly after immunization and at the termination of studies. Our data indicates that each candidate adjuvant generates a unique pattern of biomarkers as well as improved immunogenicity in the context of the DP6-001 DNA prime-protein boost vaccine. Additionally, we examined the impact of several innate signaling pathways on the adaptive immunity raised by DP6-001 and adjuvants, as well as on the unique serum cytokine profiles. These studies provide valuable information in selection of an adjuvant for inclusion in future prime-boost strategies, with the goal of enhancing immunogenicity while minimizing reactogenicity. Furthermore, these studies provided insight about the utility of different current adjuvants in a prime-boost formulation, and the unique immune environment induced by DNA priming.