Tonsillar Application of AT-2 SIV Affords Partial Protection Against Rectal Challenge With SIVmac239

Center for Biomedical Research, HIV/AIDS Program, Population Council, New York, NY, USA.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 09/2009; 52(4):433-42. DOI: 10.1097/QAI.0b013e3181b880f3
Source: PubMed


Although mucosal responses are important for preventing infections with HIV, the optimal strategies for inducing them remain unclear. To evaluate vaccine strategies targeting the oral mucosal lymphoid tissue inductive sites as an approach to provide immunity at distal sites, we vaccinated healthy macaques via the palatine/lingual tonsils with aldrithiol 2 (AT-2) inactivated Simian immunodeficiency virus (SIV)mac239, combined with CpG-C immunostimulatory oligonucleotide (CpG-C ISS-ODN, C274) as the adjuvant.
Macaques received 5 doses of C274 or control ODN C661 and AT-2 SIV on the tonsillar tissues every 6 weeks before being challenged rectally with SIVmac239, 8 weeks after the last immunization.
Although no T-cell or B-cell responses were detected in the blood before challenge, antibody (Ab) responses were detected in the rectum. Immunization with AT-2 SIV significantly reduced the frequency of infection compared with nonimmunized controls, irrespective of adjuvant. In the vaccinated animals that became infected, peak viremias were somewhat reduced. SIV-specific responses were detected in the blood once animals became infected with no detectable differences between the differently immunized groups and the controls.
This work provides evidence that vaccine immunogens applied to the oral mucosal associated lymphoid tissues can provide benefit against rectal challenge, a finding with important implications for mucosal vaccination strategies.

Download full-text


Available from: Panagiotis Vagenas,

Click to see the full-text of:

Article: Tonsillar Application of AT-2 SIV Affords Partial Protection Against Rectal Challenge With SIVmac239

507.55 KB

See full-text
  • Source
    • "In the study described here, cats repeatedly exposed to heterologous cells had reduced proviral burden when compared to cats receiving media alone following mucosal challenge with cell-associated but not cell-free FIV. While the final numbers of animals in each challenge group were relatively small (n = 4), we and others have demonstrated relevant challenge findings in the FIV and SIV animal models with final group sizes in this range [42-44]. In addition, cats mucosally exposed to heterologous cells had shifts in lymphocyte activation as well as proliferation against cellular antigens, including cells (Mya-1) that they had not been previously exposed to. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Several lines of research suggest that exposure to cellular material can alter the susceptibility to infection by HIV-1. Because sexual contact often includes exposure to cellular material, we hypothesized that repeated mucosal exposure to heterologous cells would induce an immune response that would alter the susceptibility to mucosal infection. Using the feline immunodeficiency virus (FIV) model of HIV-1 mucosal transmission, the cervicovaginal mucosa was exposed once weekly for 12 weeks to 5,000 heterologous cells or media (control) and then cats were vaginally challenged with cell-associated or cell-free FIV. Exposure to heterologous cells decreased the percentage of lymphocytes in the mucosal and systemic lymph nodes (LN) expressing L-selectin as well as the percentage of CD4+ CD25+ T cells. These shifts were associated with enhanced ex-vivo proliferative responses to heterologous cells. Following mucosal challenge with cell-associated, but not cell-free, FIV, proviral burden was reduced by 64% in cats previously exposed to heterologous cells as compared to media exposed controls. The pathogenesis and/or the threshold for mucosal infection by infected cells (but not cell-free virus) can be modulated by mucosal exposure to uninfected heterologous cells.
    Retrovirology 05/2010; 7(1):49. DOI:10.1186/1742-4690-7-49 · 4.19 Impact Factor
  • Source
    • "However, there was no commonality in the immunization routes in these three studies, as either rectal, IN, or tonsillar immunization routes were used. In two of these three articles, the route of immunization and challenge was matched [24, 25]. Although many of the other mucosally administered vaccines decreased viral replication after immunized animals became infected, none could block infection (Table 1). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The HIV vaccines tested in the halted Step efficacy trial and the modestly successful phase 3 RV144 trial were designed to elicit strong systemic immune responses; therefore, strategies to direct immune responses into mucosal sites should be tested in an effort to improve AIDS vaccine efficacy. However, as increased CD4(+) T-cell activation and recruitment to mucosal sites have the potential to enhance HIV transmission, mucosal immune responses to HIV vaccines should primarily consist of effector CD8(+) T cells and plasma cells. Controlling the level of mucosal T-cell activation may be a critical factor in developing an effective mucosal AIDS vaccine. Immunization routes and adjuvants that can boost antiviral immunity in mucosal surfaces offer a reasonable opportunity to improve AIDS vaccine efficacy. Nonhuman primate models offer the best system for preclinical evaluation of these approaches.
    Current HIV/AIDS Reports 02/2010; 7(1):19-27. DOI:10.1007/s11904-009-0035-7 · 3.80 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: More than 60 million individuals have been infected with HIV and approximately half of these individuals have died since the epidemic started. The quest for an effective vaccine to prevent HIV transmission, which is likely to be the most effective approach to halt the epidemic, has been and continues to be an insurmountable challenge. Traditional vaccine strategies that have been effective for other vaccines have proven unsuccessful or impractical for HIV because of safety concerns. Nonetheless, substantial efforts have been directed at the development and clinical testing of HIV vaccines during the past two decades. Four major HIV vaccine efficacy trials conducted by VaxGen Inc (AIDSVAX 003 and AIDSVAX 004) and the NIH-supported HIV Vaccine Trials Network (HVTN 502 and HVTN 503) failed to demonstrate efficacy; however, a recent trial conducted in Thailand (RV144 trial) demonstrated a low level of efficacy, resulting in some renewed optimism. Dissecting the causes for vaccine failure and, more importantly, for the partial level of efficacy observed in the RV144 trial should provide important guidance to the field. This review discusses the ongoing HIV vaccine trials and also highlights recent scientific advances that have provided the field with new leads to invigorate the search for effective vaccines.
    Current opinion in molecular therapeutics 02/2010; 12(1):39-46. · 3.42 Impact Factor
Show more