Characterizing the pregnancy immune phenotype: results of the viral immunity and pregnancy (VIP) study.

PURPOSE: The increased risk of morbidity and mortality from certain microbial infections and the demonstrated improvements in the clinical course of some autoimmune diseases support the existence of pregnancy-related alterations in immune status. Elucidating the changes in innate and adaptive immunity during gestation may improve pregnancy outcomes and facilitate the development of targeted therapies for autoimmune diseases. METHOD: The Viral Immunity and Pregnancy (VIP) study evaluated over 50 subjects longitudinally at three time points during pregnancy and at two time points post-delivery. Leukocyte enumeration was performed; functional responses of NK cells and CD4 T cells were analyzed, and soluble factors such as cytokines, defensins, and steroid hormones were measured in maternal blood. RESULTS: In comparison to the post-partum period, the latter part of pregnancy was characterized by significant increases in blood phagocytes and pDCs and decreases in the number and activity of NK and T cells. Alterations were found in antimicrobial proteins and serum cytokines. CONCLUSIONS: These data show that pregnancy is not a period of immunosuppression but an alteration in immune priorities characterized by a strengthening of innate immune barriers and a concomitant reduction in adaptive/inflammatory immunity in the later stages of pregnancy.

Susceptibility to Measles Among Perinatally HIV-Infected Adolescents and Young Adults.

Among our cohort of adolescents and young adults with perinatally acquired human immunodeficiency virus, few (17.6%) had measles protective antibodies by plaque reduction neutralization (PRN). Agreement was demonstrated between the commercial enzyme immunoassay and the PRN assay (K = 0.59 [95% confidence interval: 0.23-0.95]). Further studies are needed to understand the determinants of immunity in this population.

Differential profiles of immune mediators and in vitro HIV infectivity between endocervical and vaginal secretions from women with Chlamydia trachomatis infection: a pilot study.

Chlamydia trachomatis infection is one of the most prevalent bacterial STIs in the USA and worldwide, and women with C. trachomatis infection are at increased risk of acquiring HIV. Because immune activation at the genital mucosa facilitates HIV/SIV infection, C. trachomatis-mediated cytokine induction may contribute to increased HIV transmission in asymptomatic women. To begin to elucidate the mechanisms, we longitudinally analyzed profiles of innate immune factors and HIV infectivity in genital secretions from anatomically specific sites in asymptomatic women during C. trachomatis infection and post-antibiotic treatment. We found higher levels of cytokines and chemokines in endocervical secretions than vaginal secretions. Compared with the convalescent state, G-CSF, IL-1α, and RANTES were elevated in endocervical secretions, IFN-γ and TNF-α were elevated in vaginal secretions, and IFNγ, IL-1ß, and MIP1-α were elevated in cervicolavage fluid (CVL), before adjustment of multiple comparisons. Elevated endocervical levels of IP-10 and MCP-1 were associated with the use of hormonal contraception in infected women after successful treatment, suggesting the role of hormonal contraception in inflammation independent of STIs. Importantly, soluble factors found in endocervical secretions during infection enhanced HIV infectivity while no difference in HIV infectivity was found with vaginal secretions or CVL during infection or at convalescence. Taken together, the profiles of immune mediators and in vitro HIV infectivity indicate that the endocervical and vaginal mucosa are immunologically distinct. Our results underscore the importance of considering anatomical site and local sampling methodology when measuring mucosal responses, particularly in the presence of C. trachomatis infection.

Immunogenicity of trivalent inactivated influenza vaccination received during pregnancy or postpartum.

OBJECTIVE: To estimate the effects of gestational age and other maternal factors on immunologic responses to influenza vaccination. METHODS: Antepartum and postpartum women receiving influenza vaccination as part of routine clinical care were enrolled through four consecutive vaccination seasons (starting October 2006 through January 2010). Immunologic responses to trivalent inactivated influenza vaccine and monovalent H1N1 were assessed as well as factors influencing vaccine responsiveness. Serum samples were obtained at baseline and 4-8 weeks postvaccination. RESULTS: Two hundred thirty-nine participants were included in the current analysis. Seroconversion rates to trivalent inactivated influenza vaccine strains were lowest in the first trimester (54.8%) and immediately postpartum (54.8%) and were highest in the late third trimester (69.6%) and late postpartum (69.4%); these differences were not statistically significant (P=.23). In a multivariable model, higher baseline antibody levels (P<.001) and prior year flu vaccination (P=.03) were both significantly associated with reduced odds of seroconversion. Overall, results were consistent when comparing trivalent inactivated influenza vaccine and monovalent pandemic H1N1 responses. Although there was overall no significant association between gestational age at vaccination (P=.23) or prepregnancy body mass index (P=.16), we observed somewhat lower rates of seroconversion for women vaccinated in the first trimester and for obese women. CONCLUSION: Adequate immunologic responses to inactivated influenza vaccines were demonstrated during pregnancy and the postpartum period. No diminution of immunogenicity was observed in the third trimester, a time of increased clinical vulnerability to influenza.

Peripheral blood cytokine profiling during pregnancy and post-partum periods.

PROBLEM: Pregnancy requires that the maternal immune system adapt to prevent rejection of the fetal semi-allograft. This immunologic adaptation may contribute to pregnancy-related alterations in disease susceptibility and severity of infections from viral pathogens such as influenza virus. METHOD OF STUDY: As part of a larger study investigating the maternal systemic immune response during pregnancy, peripheral blood was collected three times during pregnancy and twice post-partum to measure serum levels of 23 cytokines, chemokines, and growth factors. This longitudinal study design allowed each woman's post-partum blood draw to serve as her own comparison, thus controlling for interpersonal variability in expression levels. RESULTS: When compared to the post-partum samples, significant pregnancy-related changes in IFNγ, TNFα, VEGF, GCSF, Eotaxin, and MCP-1 expression were observed. These changes have significant immunologic effects in vivo and in culture. CONCLUSION: Pregnancy-associated changes to steady state serum cytokines may have important immunologic consequence.