Intrarectal challenge of macaques vaccinated with formalin-inactivated simian immunodeficiency virus

Cranage, Martin; Baskerville, A.; Ashworth, L.A.E.; Dennis, Michael; Cook, Nicola; Sharpe, Sally; Farrar, Graham H.; Greenaway, Peter; Rose, Jane; Kitchin, P.

doi:10.1016/0140-6736(92)91335-6

Cited by 81 publications

(35 citation statements)

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“…However, it should be noted that systemic immunization with recombinant vaccinia virus vac-gp160 protected three of four macaques against intrarectal challenge with SIV mne virus 47 (39) or, in another model, cats against feline immunodeficiency virus (38). Similarly, such protection has been achieved with live attenuated virus (41,42) and whole killed virus (10). Finally, in the case of the NYVAC/SIV gpe vaccine, intramuscular immunization was previously shown to be able to protect 50% of the macaques that were challenged intrarectally with SIV mac251 from high viremia ( (7) and an even higher number of macaques when a DNA prime/NYVAC/SIV gpe boost was used (18a).…”

Section: Discussionmentioning

confidence: 99%

Both Mucosal and Systemic Routes of Immunization with the Live, Attenuated NYVAC/Simian Immunodeficiency Virus SIV_gpeRecombinant Vaccine Result in Gag-Specific CD8⁺T-Cell Responses in Mucosal Tissues of Macaques

Stevceva

Álvarez

Lackner

et al. 2002

J Virol

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As most human immunodeficiency virus (HIV) infection occurs via mucosal surfaces, an important goal of vaccination may be the induction of virus-specific immune responses at mucosal sites to contain viral infection early on. Here we designed a study in macaques carrying the major histocompatibility complex class I Mamu-A‫10ء‬ molecule to assess the capacity of the highly attenuated poxvirus NYVAC/simian immunodeficiency virus (SIV) SIV gpe vaccine candidate administered by the intranasal, intramuscular, or intrarectal route to induce mucosal immunity. All macaques, including one naive macaque, were exposed to SIV mac251 by the intrarectal route and sacrificed 48 h after infection. The kinetics of immune response at various time points following immunization with NYVAC/SIV gpe and the anamnestic response to SIV mac251 at 48 h after challenge were assessed in blood, in serial rectal and vaginal biopsy samples, and in tissues at euthanasia with an SIV mac Gag-specific tetramer. In addition, at euthanasia, antigen-specific cells producing gamma interferon or tumor necrosis factor alpha from the jejunum lamina propria were quantified in all macaques. Surprisingly, antigenspecific CD8؉ T cells were found in the mucosal tissues of all immunized macaques regardless of whether the vaccine was administered by a mucosal route (intranasal or intrarectal) or systemically. In addition, following mucosal SIV mac251 challenge, antigen-specific responses were mainly confined to mucosal tissues, again regardless of the route of immunization. We conclude that immunization with a live vector vaccine results in the appearance of CD8 ؉ T-cell responses at mucosal sites even when the vaccine is delivered by nonmucosal routes.

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Section: Discussionmentioning

confidence: 99%

Both Mucosal and Systemic Routes of Immunization with the Live, Attenuated NYVAC/Simian Immunodeficiency Virus SIV_gpeRecombinant Vaccine Result in Gag-Specific CD8⁺T-Cell Responses in Mucosal Tissues of Macaques

Stevceva

Álvarez

Lackner

et al. 2002

J Virol

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“…The viral content of seminal (Zagury et al, 1984;Ho et al, 1984;Levy et al, 1984;Krieger et al, 1991) or cervical fluids (Wofsy et al, 1986;Vogt et al, 1986) of infected individuals is very low even in terms of tissue culture infectious doses, and although a single TCIDs0 can infect a chimpanzee by the intravenous route, the number of such doses required to infect through mucosal surfaces may be very much higher, if studies with simian immunodeficiency virus (SIV) are relevant. Thus, there is a 1 : 1500 (Cranage et at., 1992) or a 1 : 10000 (Sutjipto et al, 1990) ratio of infectivity between the intravenous and mucosal routes of SIV infection in rhesus macaques. In support of this interpretation, HIV shows low transmission rates by the genital route (Holmberg et al, 1989;Blattner, 1991).…”

Section: Discussionmentioning

confidence: 99%

Antisera raised against the second variable region of the external envelope glycoprotein of human immunodeficiency virus type 1 cross-neutralize and show an increased neutralization index when they act together with antisera to the V3 neutralization epitope

Davis

Dm²,

Ca³

et al. 1993

Journal of General Virology

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Antibodies have been raised against a synthetic peptide (IRDKIQKENALFRNL) containing a neutralizing epitope within the second variable region of the human immunodeficiency virus type 1 (HIV-1) SF2 strain external envelope glycoprotein (gpl20) and also against equivalent peptides of the HIV-1 LAI, RF and MN isolates. The resulting antisera cross-react with heterologous peptides but binding to heterologous recombinant gpl20 is more restricted. Antisera to HIV-1 SF2, RF and MN are able to neutralize homologous virus.Some cross-neutralization is also observed, but a consensus peptide failed to induce neutralizing antibodies to any of the isolates studied. Antibodies to the V2 and V3 epitopes give a higher neutralization index when acting together than when the individual sera are used alone. Antibodies induced in natural infection bind to two sets of hexamers within the region encompassed by the 15-mer peptide, and the response to these can differ between infected individuals and within the same host over time.

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“…Of great significance in this connection are the following: tInfection of rhesus macaques by a cell-free SIV by the rectal route was recently reported to require 1500 times more virus than by the intravenous route (34). ofpatients who died ofAIDS.…”

Section: Effect Of Antibodies Against Hiv In Infected Personsmentioning

confidence: 99%

Improbability of effective vaccination against human immunodeficiency virus because of its intracellular transmission and rectal portal of entry.

Sabin¹

1992

Proc. Natl. Acad. Sci. U.S.A.

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The worldwide effort to produce a vaccine against AIDS continues to disregard the fact that even human immunodeficiency virus (HIV)-specific neutralizing antibodies and cell-mediated immunity are ineffective against virus within cells without viral antigens on the cell membrane--and that much of HIV infection is transmitted in this manner. According to a recent report, a simian immunodeficiency virus vaccine that protected monkeys against an intravenous challenge with cell-free virus was, as predicted, ineffective against an intravenous challenge with the same amount of virus in infected cells. Moreover, antibody and HIV have been found to coexist in cell-free plasma from asymptomatic and symptomatic patients. Excluding direct introduction of HIV into the blood-stream, the most common and efficient form of transmission of HIV infection is by receptive anal intercourse, and semen contains large numbers of infected cells per milliliter. Recent reports showing that colorectal cells can be persistently infected by HIV and that HIV RNA and cDNA are present in the cells of the colon of dead AIDS patients indicate that either cell-free or intracellular HIV has the capacity to multiply at the portal of entry in the colorectal area without interference from neutralizing antibodies. The available data provide no basis for testing any HIV vaccine in human beings either before or after infection. The main challenge is to find a way to kill cells with chromosomally integrated HIV cDNA without harming normal cells, perhaps by identifying repressor proteins that might be produced by the cells with integrated HIV cDNA and thus could become specific targets for cell-killing drugs.

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Intrarectal challenge of macaques vaccinated with formalin-inactivated simian immunodeficiency virus

Cited by 81 publications

References 5 publications

Both Mucosal and Systemic Routes of Immunization with the Live, Attenuated NYVAC/Simian Immunodeficiency Virus SIV_gpeRecombinant Vaccine Result in Gag-Specific CD8⁺T-Cell Responses in Mucosal Tissues of Macaques

Both Mucosal and Systemic Routes of Immunization with the Live, Attenuated NYVAC/Simian Immunodeficiency Virus SIV_gpeRecombinant Vaccine Result in Gag-Specific CD8⁺T-Cell Responses in Mucosal Tissues of Macaques

Antisera raised against the second variable region of the external envelope glycoprotein of human immunodeficiency virus type 1 cross-neutralize and show an increased neutralization index when they act together with antisera to the V3 neutralization epitope

Improbability of effective vaccination against human immunodeficiency virus because of its intracellular transmission and rectal portal of entry.

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Intrarectal challenge of macaques vaccinated with formalin-inactivated simian immunodeficiency virus

Cited by 81 publications

References 5 publications

Both Mucosal and Systemic Routes of Immunization with the Live, Attenuated NYVAC/Simian Immunodeficiency Virus SIVgpeRecombinant Vaccine Result in Gag-Specific CD8+T-Cell Responses in Mucosal Tissues of Macaques

Both Mucosal and Systemic Routes of Immunization with the Live, Attenuated NYVAC/Simian Immunodeficiency Virus SIVgpeRecombinant Vaccine Result in Gag-Specific CD8+T-Cell Responses in Mucosal Tissues of Macaques

Antisera raised against the second variable region of the external envelope glycoprotein of human immunodeficiency virus type 1 cross-neutralize and show an increased neutralization index when they act together with antisera to the V3 neutralization epitope

Improbability of effective vaccination against human immunodeficiency virus because of its intracellular transmission and rectal portal of entry.

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Both Mucosal and Systemic Routes of Immunization with the Live, Attenuated NYVAC/Simian Immunodeficiency Virus SIV_gpeRecombinant Vaccine Result in Gag-Specific CD8⁺T-Cell Responses in Mucosal Tissues of Macaques

Both Mucosal and Systemic Routes of Immunization with the Live, Attenuated NYVAC/Simian Immunodeficiency Virus SIV_gpeRecombinant Vaccine Result in Gag-Specific CD8⁺T-Cell Responses in Mucosal Tissues of Macaques