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Science Advances

FY 2013

NIAID conducts and supports research to prevent, diagnose, and treat infectious and immunological diseases that affect the health of women and girls.

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Parasitic Infectious Diseases

Preventive Treatment Strategy in Pregnant Women Is Associated With Higher Malaria Risk for Their Children

Intermittent treatment with a drug combination called sulfadoxine-pyrimethamine has been used to prevent many harmful consequences of malaria infection during pregnancy. However, it fails to prevent placental malaria, a common complication of malaria in pregnancy, in areas of the world where resistance to these drugs is widespread. A longitudinal study in Tanzania led by NIAID researchers demonstrated for the first time that this treatment strategy was associated with a higher risk of malaria infection and severe malarial disease in children born to women who had placental malaria. The findings could have important implications for malaria control efforts worldwide.

Reference: Harrington WE, Morrison R, Fried M, et al. Intermittent preventive treatment in pregnant women is associated with increased risk of severe malaria in their offspring. PLoS One. 2013;8(2):e56183.

 

Viral Infectious Diseases (Other Than HIV/AIDS)

Experimental Vaccine Strategy Shows Promise Against Genital Herpes

This NIAID-funded study used a mouse model to develop a novel vaccination strategy against herpes simplex virus 2 that relies on T-cell activation rather than neutralizing antibody production. Known as “prime and pull,” the first step is a conventional vaccination to activate T cells throughout the body (prime). This is followed by the application of a small molecule to the genital area, which draws in the activated T cells (pull). These cells establish a niche in the tissue and are ready to provide protection against future infection.

Reference: Shin H and Iwasaki A. A vaccine strategy that protects against genital herpes by establishing local memory T cells. Nature. 2012 Nov 15; 491(7424):463-7.

Frequent Detection of Human Papillomavirus in HIV-Infected Women in Uganda

A team led by researchers from NIAID and their colleagues examined the frequency of cervical human papillomavirus (HPV) detection among HIV-infected women in a resource-limited setting in Uganda. The women were followed monthly for six months before and after initiation of antiretroviral therapy (ART). The researchers did not observe an effect of ART on monthly HPV detection, even if the women’s immune systems became healthier or HIV replication was suppressed. They found that only older age and higher pre-ART numbers of CD4+ immune cells, which are targeted by HIV, were associated with a significantly lower risk of detecting HPV. The results highlight the importance of continued and consistent screening for HPV, even after starting ART.

Reference: Rositch AF, Gravatt PE, Tobian AA, et al. Frequent detection of HPV before and after initiation of antiretroviral therapy among HIV/HSV-2 co-infected women in Uganda. PLoS One. 2013;8(1):e55383.

 

Human Immunology

Insights on the Human Vaginal Immune Response in Health and Disease

The human vaginal mucosa is a major entry site for sexually transmitted pathogens, but the immunological responses within the vagina are poorly understood. NIAID-supported researchers demonstrated that the earliest immune responses in the vagina can be orchestrated by the activation of four different immune cell types. Each cell type then directs the production of different T cells that provide protective immune responses. The results of this study provide insights that will lead to the design and development of effective mucosal vaccines against many sexually transmitted diseases.

Reference: Duluc D, Gannevat J, Anguiano E. Functional diversity of human vaginal APC subsets in directing T-cell responses. Mucosal Immunol. 2013 May;6(3):626-38.

Progesterone Promotes the Stability of Immune Cells With Therapeutic Potential

Regulatory T cells (Tregs) actively suppress activation of the immune system and prevent inflammation. A subset of Tregs, known as induced T-regulatory (iTreg) cells, are difficult to study because they are unstable. Using animal models, NIAID-funded investigators found that progesterone, a female hormone, can generate highly stable iTreg cells that are efficient in suppressing tissue inflammation. These results show great therapeutic promise for autoimmune diseases such as multiple sclerosis and inflammatory bowel disease.

Reference: Lee JH, Lydon JP, Kim CH, et al. Progesterone suppresses the mTOR pathway and promotes generation of induced regulatory T cells with increased stability. Eur J Immunol. 2012 Oct;42(10):2683-96.

 

HIV/AIDS

Statistical Method Shows Relationships Between Tissue Drug Concentrations and Effectiveness of an Anti-HIV Microbicide

Researchers funded by NIAID created a new statistical model that allowed further analysis of data from an early-phase safety study of the vaginally formulated UC781 gel as a rectal microbicide to prevent HIV acquisition. This new statistical method allowed researchers to determine specific relationships between tissue drug concentrations and the effectiveness of UC781 in a biopsy challenge model, which tests the ability of HIV to infect small samples (biopsies) of rectal tissue from patients. This work provided the first estimate of the concentration of drug in gel that might be required to prevent HIV transmission and identified the biopsy challenge model as a potential bridge to link drug concentration in tissues with possible efficacy of the drug.

Reference: Richardson-Harman N, Mauck C, McGowan I, et al. Dose-response relationship between tissue concentrations of UC781 and explant infectibility with HIV type 1 in the RMP-01 rectal safety study. AIDS Res Hum Retroviruses. 2012 Nov;28(11):1422-33.

Multifaceted Approach Could Help Estimate HIV Incidence

Reliable and cost-effective methods to estimate HIV incidence help monitor the epidemic, identify at-risk populations, and evaluate prevention strategies. NIAID-supported scientists compared three methods for estimating the HIV incidence rate in more than 2,000 women enrolled in the HIV Prevention Trials Network 064 study. They found that the annual HIV incidence estimate based on acute infection at enrollment was tenfold higher than the incidence estimate based on the time when participants developed an immune response to HIV or on a new method that uses an algorithm that combines the results of several lab tests. This preliminary evidence suggests that the new approach could be useful in estimating HIV incidence.

Reference: Eshleman SH, Hughes JP, Laeyendecker O, et al. Use of a multifaceted approach to analyze HIV incidence in a cohort study of women in the United States: HIV Prevention Trials Network 064 Study. J Infect Dis. 2013 Jan 15;207(2):223-31.

Risk Factors for HIV Acquisition Among Women From Selected Areas of the United States

An NIAID-funded study evaluated HIV incidence and described behaviors for up to 12 months among U.S. women living in communities with high HIV prevalence and high poverty rates. Among 2,099 high-risk women aged 18 to 44 years (85.9 percent black and 11.7 percent of Hispanic ethnicity), 32 were diagnosed with HIV infection at the time of enrollment. The annual incidence of HIV was 0.32 percent. Older age, substance use, and having an HIV-infected partner were associated with high HIV prevalence. This study enrolled a cohort of women with a substantially higher HIV incidence rate than the national estimate in the general population of U.S. black women.

Reference: Hodder SL, Justman J, Hughes JP, et al. HIV acquisition among women from selected areas of the United States: a cohort study. Ann Intern Med. 2013 Jan 1;158(1):10-8.

See earlier research overviews.

Last Updated November 21, 2013

Last Reviewed November 21, 2013