Most successful vaccines elicit antibodies that protect against infection. In this issue of Immunity, Bomsel et al. (2011) show in the rhesus macaque model that vaccine-induced mucosal antibodies, rather than circulating neutralizing antibodies, may be critical components for protective immunity against HIV-1.
"Indeed, genital IgA and IgG, elicited through combined intra-muscular and intranasal vaccination against HIV-gp41, delivered via virosome in nonhuman primates, prevented systemic HIV invasion by blocking transcytosis and by mediating antibody-dependent cellular cytotoxicity (ADCC) . These animals lacked serum-neutralizing antibody activity, highlighting the role of effector antibodies at the mucosal point of entry, and their importance in preventing the dissemination of HIV infection . In humans, the RV144 vaccine regimen (canarypox prime, HIV gp120 envelope (Env) glycoprotein boost) elicits protective responses, the nature of which remains to be defined in terms of generation and effector mechanisms . "
[Show abstract][Hide abstract] ABSTRACT: Understanding how the mucosal immune system in the human female reproductive tract might prevent or facilitate HIV infection has important implications for the design of effective interventions. We and others have established cohorts of highly-exposed, HIV-seronegative individuals, such as HIV-uninfected commercial sex workers, who have remained HIV-negative after more than 5 years of active prostitution. Observations obtained in studies of such individuals, who represent a model of natural immunity to HIV, indicate that HIV resistance may be associated with the host's capacity to preserve systemic integrity by constraining immune activity and controlling inflammatory conditions at the mucosal point of entry. This likely necessitates the orchestration of balanced, first-line and adaptive immune responses.
"In support of this are the recent findings by Bomsel et al. demonstrating that mucosal IgA and IgG, elicited through mucosal vaccination with HIV-1 gp41 subunit virosomes in nonhuman primates, prevented systemic invasion following vaginal simian-HIV challenge, by blocking transcytosis and by mediating antibody-dependent cellular cytotoxicity (ADCC) . Importantly, these animals lacked serum neutralizing antibody activity, highlighting the role of effector antibodies at the mucosal portal of entry, and their importance in preventing dissemination of HIV infection . In humans, the Thai RV144 vaccine trial has been raising some hope. "
[Show abstract][Hide abstract] ABSTRACT: Dendritic cells (DCs) modulate B-cell differentiation, activation, and survival mainly through production of growth factors such as B lymphocyte stimulator (BLyS/BAFF). DC populations have been reported to be affected in number, phenotype and function during HIV infection and such alterations may contribute to the dysregulation of the B-cell compartment. Herein, we reflect on the potential impact of DC on the pathogenesis of HIV-related B cell disorders, and how DC status may modulate the outcome of mucosal B cell responses against HIV, which are pivotal to the control of disease. A concept that could be extrapolated to the overall outcome of HIV disease, whereby control versus progression may reside in the host's capacity to maintain DC homeostasis at mucosal sites, where DC populations present an inherent capacity of modulating the balance between tolerance and protection, and are amongst the earliest cell types to be exposed to the virus.
[Show abstract][Hide abstract] ABSTRACT: Mucosal surfaces are a major portal of entry for many human pathogens that are the cause of infectious diseases worldwide. Vaccines capable of eliciting mucosal immune responses can fortify defenses at mucosal front lines and protect against infection. However, most licensed vaccines are administered parenterally and fail to elicit protective mucosal immunity. Immunization by mucosal routes may be more effective at inducing protective immunity against mucosal pathogens at their sites of entry. Recent advances in our understanding of mucosal immunity and identification of correlates of protective immunity against specific mucosal pathogens have renewed interest in the development of mucosal vaccines. Efforts have focused on efficient delivery of vaccine antigens to mucosal sites that facilitate uptake by local antigen-presenting cells to generate protective mucosal immune responses. Discovery of safe and effective mucosal adjuvants are also being sought to enhance the magnitude and quality of the protective immune response.
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