Deborah Anderson

Boston University | BU · Department of Obstetrics and Gynecology

Background Approximately 40% of human pregnancies are unintended, indicating a need for more acceptable effective contraception methods. New antibody production systems make it possible to manufacture reagent-grade human monoclonal antibodies (mAbs) for clinical use. We used the Nicotiana platform to produce a human antisperm mAb and tested its eff...

Background MB66 film is a multipurpose prevention technology (MPT) product with monoclonal antibodies (mAbs) against HIV-1 (VRC01-N) and HSV-1 and 2 (HSV8-N). The mAbs were produced by transient expression in Nicotiana benthamiana (N). We conducted a Phase I clinical trial to assess the safety, pharmacokinetics (PK), and ex vivo efficacy of single...

Sexually transmitted infections are highly prevalent, and over 40% of pregnancies are unplanned. We are producing new antibody-based multipurpose prevention technology products to address these problems and fill an unmet need in female reproductive health. We used a Nicotiana platform to manufacture monoclonal antibodies against two prevalent sexua...

Background: Condylomata acuminata [anogenital warts (AGW)] are prevalent in HIV-infected individuals and sexually active populations at risk for HIV acquisition, and have been associated with HIV transmission. We compared AGW to control tissue for abundance, types and location of HIV-target cells, and for susceptibility to HIV infection in vitro,...

Passive immunization has been used since the late 1800’s to prevent and treat human infectious diseases. Administration of animal immune sera and human immunoglobulin has given way to the use of monoclonal antibodies (mAbs) for passive immunization, and highly potent broadly neutralizing anti-HIV antibodies (bNAbs) are now being considered for HIV...

Background: Rhesus and cynomologus macaques are valuable animal models for the study of human immunodeficiency virus (HIV) prevention strategies. However, for such studies focused on the vaginal route of infection, differences in vaginal environment may have deterministic impact on the outcome of such prevention, providing the rationale for this s...

Passive immunization, the transfer of antibodies to a nonimmune individual to provide immunological protection, has been used for over 100 years to prevent and treat human infectious diseases. The introduction of techniques to produce human monoclonal antibodies (mAbs) has revolutionized the field, and a large number of human mAbs have been license...

The broadly neutralizing antibody (bNAb) VRC01, capable of neutralizing 91% of known HIV-1 isolates in vitro , is a promising candidate microbicide for preventing sexual HIV infection when administered topically to the vagina; however, accessibility to antibody-based prophylactic treatment by target populations in sub-Saharan Africa and other under...

Objective: Pre-ejaculatory fluid, a viscous, lubricating secretion expressed by penile urethral glands during sexual excitement, may play a role in the sexual transmission of HIV-1. The urethra has been shown to be an important site of HIV infection in men and macaques, and pre-ejaculatory fluid and urethral swabs from HIV-1 infected men often con...

The male genital tract has characteristics of the mucosal immune system as well as systemic immunity. Most regions are capable of local innate and acquired immunity; in addition, systemic immunoglobulins and cells also participate in male genital immune defense. The penile urethra and prostate are active regions with a capacity for local immunoglob...

Trichomonas vaginalis causes vaginitis and increases the risk of HIV transmission by heterosexual sex, while Tritrichomonas foetus causes premature abortion in cattle. Our goals were to determine the effects, if any, of anti-retroviral lectins, which are designed to prevent heterosexual transmission of HIV, on adherence of Trichomonas to ectocervic...

Human seminal plasma contains factors that can regulate the female immune system and potentially promote reproductive fitness. Adverse effects on fertility and pregnancy may occur when seminal plasma provides insufficient, excessive, or altered signals or when the female partner is incapable of receiving these signals.

Estrogen and progesterone regulate proliferation and differentiation of epithelial cells in the female genital tract. We investigated the effects of these hormones on reconstructed human organotypic vaginal epithelial tissue models (EpiVaginal). We ascertained that epithelial cells in the tissue models express estrogen and progesterone receptors. T...

This supplement to The Journal of Infectious Diseases is devoted to the important and understudied topic of cell-associated human immunodeficiency virus Type 1 (HIV) mucosal transmission. It stems from a workshop held in Boston, Massachusetts, in October 2013, in which scientists discussed their research and insights regarding cell-associated HIV m...

Human immunodeficiency virus type 1 (HIV-1) can efficiently spread by direct cell-to-cell contact, a mechanism termed cell-associated HIV transmission. By some estimates, cell-associated HIV transmission is 10-1000-fold more effective than cell-free HIV infection. Mucosal cell-associated HIV transmission may occur when HIV-bearing cells in mucosal...

Human immunodeficiency virus (HIV)-infected leukocytes have been detected in genital secretions from HIV-infected men and women and may play an important role in the sexual transmission of HIV. However, they have been largely overlooked in studies on mechanisms of HIV transmission and in the design and testing of HIV vaccine and microbicide candida...

Methods: HSV2 prevalence at enrollment and incidence at 24 months on study were determined by validated western blot assay. HIV-1 testing occurred at specified intervals and RNA PCR was used to confirm HIV-1 infection. Multivariate logistic regression modeling was used to investigate associations. Results: HSV2 prevalence at enrollment was 31% (248...

Topical microbicides are a leading strategy for prevention of HIV mucosal infection to women; however, numerous pharmacokinetic limitations associated with coitally related dosing strategy have contributed to their limited success. Here we test the hypothesis that adeno-associated virus (AAV) mediated delivery of the b12 human anti-HIV-1 gp120 mini...

The superficial layers of the human vaginal epithelium, which form an interface between host and environment, are comprised of dead flattened cells that have undergone a terminal cell differentiation program called cornification. This entails extrusion of nuclei and intercellular organelles, and the depletion of functional DNA and RNA precluding th...

We read with interest the recent paper by Hadas et al., titled “Transmission of chimeric HIV by mating in conventional mice: prevention by pre-exposure antiretroviral therapy and reduced susceptibility during estrus”, first published online on July 25, 2013 (ahead of print) in Disease Models &

Author Summary HIV-1 causes a sexually transmitted disease. However, the mechanisms employed by the virus to cross genital tract tissue and establish infection are uncertain. Since cervicovaginal fluid is acidic and HIV-1 in cervicovaginal fluid is likely coated with antibodies, we explored the effect of low pH and HIV-1-specific antibodies on tran...

[This corrects the article on p. e1003776 in vol. 9.].

Self-administered swabs are used to sample vaginal contents for a variety of clinical purposes including detection of sexually transmitted infections, condom breakage, and vaginal product use. The goal of this study was to determine whether a quantitative glycogen assay can be used to assess whether a swab has been exposed to the vagina to assure s...

Although HAART can suppress genital shedding and sexual transmission of HIV, men who have sex with men (MSM) have experienced a resurgent HIV epidemic in the HAART era. Many HIV-infected MSM continue to engage in unsafe sex, and sexually transmitted infections (STIs) or other factors may promote genital HIV shedding and transmission in this populat...

Although cervico-vaginal epithelial cells of the female lower genital tract provide the initial defense system against HIV-1 infection, the protection is sometimes incomplete. Thus, enhancing anti-HIV-1 humoral immunity at the mucosal cell surface by local expression of anti-HIV-1 broadly neutralizing antibodies (BnAb) that block HIV-1 entry would...

The mucosal epithelium is a major portal for microbial invasion. Mucosal barrier integrity is maintained by the physical interactions of intercellular junctional molecules on opposing epithelial cells. The epithelial mucosa in the female reproductive tract provides the first line of defense against sexually transmitted pathogenic bacteria and virus...

Recent evidence that circumcision decreases HIV infection in heterosexual men by 50-60% has focused research on the foreskin as a target of HIV infection. In this review article, we discuss potential mechanisms underlying the circumcision effect and re-examine the assumption that the foreskin is the principle penile HIV infection site. HIV target c...

In men, the penile urethra is a primary infection site for sexually transmitted pathogens. Research on the immunology of this mucosal site has been limited in part due to sampling challenges, but available evidence indicates that the urethra contains a rich contingent of immunological mediators that can mount vigorous innate and adaptive immune res...

cells of the innate immune system use Toll-like receptors (TLRs) to recognize and respond to invading pathogens. This study was carried out to characterize TLR expression in the human male genital tract, an initial infection site for several sexually transmitted pathogens. immunohistochemistry was used to detect expression of TLRs 1-9 in genital tr...

The vaginal mucosa is commonly exposed to chemicals and therapeutic agents that may result in irritation and/or inflammation. In addition to acute effects, vaginal irritation and inflammation can make women more susceptible to infections such as HIV-1 and herpes simplex virus 2 (HSV-2). Hence, the vaginal irritation potential of feminine care formu...

This chapter emphasizes that highly effective HIV prevention strategies depend upon an in-depth appreciation of the sophisticated interactions between HIV and host mucosal immune defense. HIV through sexual transmission occurs when HIV in genital secretions from an infected sex partner breech the mucosal epithelium of an uninfected partner to estab...

Acute gonorrhea in women is characterized by a mucopurulent exudate that contains polymorphonuclear leukocytes (PMNs) with intracellular gonococci. Asymptomatic infections are also common. Information on the innate response to Neisseria gonorrhoeae in women is limited to studies with cultured cells, isolated immune cells, and analyses of cervicovag...

Objective Diaphragms are being considered for use with vaginal microbicide gels to provide enhanced protection against sexually transmitted pathogens. The purpose of this study was to determine whether use of a diaphragm with microbicide or placebo gel causes cervicovaginal inflammation or perturbations in cervicovaginal immune defense. Method of s...

Information concerning the effects of HIV-1 infection, disease progression, and antiretroviral therapy (ART) on male genital white blood cell (WBC) profiles could provide important insight into genital immune defense in HIV-infected men and seminal HIV transmission mechanisms. To compare concentrations of WBC populations in semen from HIV-1-seroneg...

In this study we investigated whether elevated levels of the inflammatory mediator granulocyte elastase in seminal plasma were associated with increased numbers of CD4+ T helper/inducer lymphocytes and monocytes/macrophages in semen, the principal host cells of the human immunodeficiency virus (HIV). Semen samples were obtained from 105 men attendi...

Deborah Anderson explains why women really shouldn’t rely on Coca-Cola for family planning

The purpose of this study was to establish normal reference values for several immunologic factors in semen to provide a foundation for understanding their physiologic significance in health and disease. Semen from 83 healthy, fertile men was assessed by Bio-Plex or enzyme-linked immunosorbent assay to determine quantities of immunoglobulin (Ig) is...

To determine the prevalence of pathogens that cause sexually transmitted infections (STIs) in semen from asymptomatic male infertility patients with and without leukocytospermia (LCS), and associations between STIs, inflammatory markers, and other semen variables. Retrospective, controlled study. Academic Medical Center. Two hundred and forty-one m...

To examine the relationship between selenium nutritional status and intermediates of human immunodeficiency virus (HIV)-1 transmission. Prospective cohort study. A study clinic at Muhimbili National Hospital, Dar es Salaam, Tanzania. A total of 340 HIV-1-infected pregnant women with gestational ages 12-27 weeks. Women's plasma selenium concentratio...

The mucosal lymphocyte population is the largest in the body, and the gastrointestinal compartment has been well characterized in HIV infection. Much less is known about the effects of HIV on the genital tract. : To examine the T-lymphocyte phenotype and receptor repertoire as well as total and virus-specific immunoglobulin concentrations in the en...

We investigated progesterone (P) signaling in human leukemia cells, shown to downregulate cytokines with P. The following tests were utilized: PCR with FAM labeled primers and Gene Scan with the Applied Biosystems 373 DNA sequencer for progesterone receptor (PR) mRNA, immunohistochemistry using monoclonal antibodies (Zymed and Ventana) for PR prote...

Mucins are large, hydrophilic glycoproteins that protect wet-surfaced epithelia from pathogen invasion as well as provide lubrication. At least 17 mucin genes have been cloned to date. This study sought to determine the mucin gene expression profile of the human male urogenital tract epithelia, to determine if mucins are present in seminal fluid an...

A three-dimensional organotypic vaginal-ectocervical (VEC) tissue model has been developed to test the irritation of topically applied spermicides, microbicides, and vaginal-care products. The in vitro tissue model was reconstructed using normal VEC epithelial cells and is well stratified, containing differentiated basal, suprabasal, intermediate,...

Couples in whom the man is HIV-1-positive may use medically assisted procreation in order to conceive a child without contaminating the female partner. But, before medically assisted procreation, the semen has to be processed to exclude HIV and tested for HIV nucleic acid before and after processing. The performance was evaluated of the technical p...

Women with recurrent pregnancy loss (RPL) and T-helper (Th)1-type immunity to trophoblast antigens have an increased frequency of the IL1B-511*1 promoter variant. Since CD46 gene products also regulate maternal immune responses including Th1 immunity, we investigated whether CD46 gene polymorphisms are also associated with RPL in women with and wit...

Microbicides must protect against STD pathogens without causing unacceptable toxic effects. Microbicides based on nonoxynol-9 (N9) and other detergents disrupt sperm, HSV and HIV membranes, and these agents are effective contraceptives. But paradoxically N9 fails to protect women against HIV and other STD pathogens, most likely because it causes to...

Erythrocyte complement receptor type 1 (E-CR1) is the main immune complex clearance mechanism in humans. Decreased E-CR1 expression is noted in certain inflammatory disorders. Recent evidence implicates inflammation in the pathogenesis of preeclampsia. We investigated whether E-CR1 is decreased in preeclampsia. E-CR1 protein expression was quantifi...

Cell-mediated immunity (CMI) is key to defense against intracellular pathogens such as Chlamydia trachomatis and viruses that infect the lower female genital tract, but little is known about CMI at this site. Recent studies indicate that there are immunological microenvironments within the female genital tract, and that immune functions are affecte...

This chapter discusses the immunoanatomy of the human male urogenital tract, the naturally occurring immune responses, changes in genital tract immune profiles with disease, the effects of androgens on immunity, and the genital tract vaccination studies, with prospects for future research. The human male genital tract consists of a single contiguou...

Episomal 2-long terminal repeat (LTR) HIV-1 cDNA, a by-product of HIV-1 infection, is used in clinical trials as a marker for ongoing viral replication. It would be useful to employ 2-LTR cDNA to monitor cryptic HIV-1 infection in the genital tract of men on antiretroviral therapy (ART) to predict the evolution of sexually transmissible drug-resist...

To determine whether cytokines implicated in uterine receptivity are detectable in cervicovaginal secretions and/or serum of fertile women, and whether their concentrations undergo hormonal regulation during the menstrual cycle. Prospective, observational study. Academic medical center. Six fertile volunteers studied over two menstrual cycles. Cerv...

Cervical cytobrushes provide a tool to sample endocervical T cells for assessment of local immunity. However, most previous studies in HIV-seropositive women have excluded samples containing blood and hence have analyzed selected populations of patients. As determined by multiple-parameter flow cytometric analysis of T lymphocytes from two sequenti...

Micronutrient status has been associated with shedding of human immunodeficiency virus type 1 (HIV-1) in the lower-genital tract in observational studies. We examined the effect of vitamin supplements on genital HIV-1 shedding and interleukin-1β (IL-1β), a cytokine marker of vaginal inflammation and promotion of HIV-1 infection. Consenting HIV-1–in...

To compare a new sperm-processing device, utilizing a double tube and gradient, with other commonly used sperm-processing methods for their abilities to exclude human immunodeficiency virus type 1 (HIV-1) from the motile sperm fraction while retaining maximum sperm yield. Laboratory experiments. Academic research environment. Healthy HIV-1 seronega...

Infection of cervical keratinocytes by high-risk HPV is involved in the etiology of cervical carcinoma. Since viral products are immunogenic, development of cancer may require suppression of immune responses directed against infected epithelial cells. Many markers of host immune effector responses decrease as cervical intraepithelial neoplasia prog...

To determine the association between genital tract shedding of human immunodeficiency virus (HIV) type 1 and vertical transmission, a case-control substudy was conducted within the Women and Infants Transmission Study. Antenatal cervicovaginal lavage specimens were assessed for HIV-1 RNA in the supernatant and HIV-1 RNA and DNA in cell pellets. Mul...

This paper reviews the latest reproductive options for HIV infected couples. In light of the new treatment options and improved prognosis for HIV patients, policymakers have issued recent statements to guide physicians in the care of HIV patients desiring fertility. We will review the advances in reproductive technologies and ethical considerations...

In experiments to assess the in vitro impact of the candidate microbicides nonoxynol 9 (N-9), C31G, and sodium dodecyl sulfate (SDS) on human immune and epithelial cell viability, cell lines and primary cell populations of lymphocytic and monocytic origin were generally shown to be equally sensitive to exposures ranging from 10 min to 48 h. However...

Relatively little is known about sites of HIV infection and regulation of the infection in the genital tract. It is imperative to understand the mechanisms of HIV-1 infection of the genital tract to develop methods to control HIV-1 transmission. New methods are being developed through use of assisted reproductive technologies. These approaches incl...

Toll-like receptors (TLRs) have recently been identified as fundamental components of the innate immune response to bacterial pathogens. We investigated the role of TLR signaling in immune defense of the mucosal epithelial cells of the lower female genital tract. This site provides first line defense against microbial pathogens while remaining tole...

Recurrent pregnancy loss (RPL) is a common disorder during early gestation. Recent evidence suggests that T helper 1 (Th1)-type immunity is associated with unsuccessful pregnancy especially in women with RPL of otherwise unknown etiology, while Th2-type immunity is associated with pregnancy success. Interleukin (IL)-1 may influence Th1/Th2 immune r...

New approaches being developed to prevent HIV infection in women include treatment of STDs; sperm-washing techniques for HIV-1-infected partners, provided in conjunction with artificial insemination; in vitro fertilization; vaginal microbicides; and HIV-1 vaccines.

Topical microbicides are being sought to prevent sexually transmitted diseases by inactivating pathogens while preserving or enhancing the natural mucosal barrier. Serious public health concerns were raised by a recent phase 3 clinical trial that showed that nonoxynol-9 (N-9), a leading microbicide candidate widely used as an over-the-counter sperm...