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.

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Available from: Panagiotis Vagenas, Sep 30, 2015
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    • "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. "
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    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; 7:49. DOI:10.1186/1742-4690-7-49 · 4.19 Impact Factor
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    • "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). "
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    Current HIV/AIDS Reports 02/2010; 7(1):19-27. DOI:10.1007/s11904-009-0035-7 · 3.80 Impact Factor
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    ABSTRACT: There are currently over thirty million people infected with HIV and there are no vaccines available to prevent HIV infections or disease. The genitourinary, rectal and oral mucosa are the mucosal HIV transmission routes. An effective vaccine that can induce both systemic and local mucosal immunity is generally accepted as a major means of protection against mucosal HIV transmission and AIDS. Structure and cells that comprise the oral, vaginal and rectal mucosa pertaining to HIV transmission and vaccination strategies through each mucosal route to prevent mucosal and systemic infection will be discussed. Covering publications from 1980s through 2010, mucosal transmission of HIV and current and previous approaches to vaccinations are discussed. Although oral transmission of HIV is far less common than vaginal and rectal transmissions, infections through this route do occur through oral sex as well as vertically from mother to child. Mucosal vaccination strategies against oral and other mucosal HIV transmissions are under intensive research but the lack of consensus on immune correlates of protection and lack of safe and effective mucosal adjuvants and delivery systems hamper progress towards a licensed vaccine.
    Expert opinion on biological therapy 08/2010; 10(8):1181-95. DOI:10.1517/14712598.2010.496776 · 3.74 Impact Factor
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