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Role of complement and antibodies in controlling infection with pathogenic simian immunodeficiency virus (SIV) in macaques vaccinated with replication-deficient viral vectors.

Falkensammer B, Rubner B, Hiltgartner A, Wilflingseder D, Stahl Hennig C, Kuate S, Uberla K, Norley S, Strasak A, Racz P, Stoiber H - Retrovirology (2009)

Bottom Line: The vaccine was applied via spray-immunization to the tonsils of rhesus macaques and compared with systemic regimens.Independent of the application regimen or route, viral loads were significantly reduced after challenge with SIVmac239 (p < 0.03) compared to controls.In contrast, the amount of the observed complement-mediated lysis did not correlate with the reduction of SIV titres.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Hygiene, Microbiology and Social Medicine, Innsbruck Medical University, 6020 Innsbruck, Austria. barbara.falkensammer@i-med.ac.at

ABSTRACT

Background: We investigated the interplay between complement and antibodies upon priming with single-cycle replicating viral vectors (SCIV) encoding SIV antigens combined with Adeno5-SIV or SCIV pseudotyped with murine leukemia virus envelope boosting strategies. The vaccine was applied via spray-immunization to the tonsils of rhesus macaques and compared with systemic regimens.

Results: Independent of the application regimen or route, viral loads were significantly reduced after challenge with SIVmac239 (p < 0.03) compared to controls. Considerable amounts of neutralizing antibodies were induced in systemic immunized monkeys. Most of the sera harvested during peak viremia exhibited a trend with an inverse correlation between complement C3-deposition on viral particles and plasma viral load within the different vaccination groups. In contrast, the amount of the observed complement-mediated lysis did not correlate with the reduction of SIV titres.

Conclusion: The heterologous prime-boost strategy with replication-deficient viral vectors administered exclusively via the tonsils did not induce any neutralizing antibodies before challenge. However, after challenge, comparable SIV-specific humoral immune responses were observed in all vaccinated animals. Immunization with single cycle immunodeficiency viruses mounts humoral immune responses comparable to live-attenuated immunodeficiency virus vaccines.

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IgG response to the viral env-proteins. During vaccination, SIV-specific IgG antibodies targeting the envelope were determined in all vaccine groups and in the control group after challenge with SIVmac239. For this assay SIVmac251 infected HSC-F were incubated with heat-inactivated sera from vaccinated and infected animals. SIV-specific antibodies bound to infected T-cells were stained with a FITC-labelled anti-human IgG and determined by flow cytometry. Values are given as mean fluorescence intensities (MFI). Dotted arrows mark points in time of boosts and additional asterisks refer to boosts of group 1 only, whereas the black arrow indicates the point in time of challenge.
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Figure 2: IgG response to the viral env-proteins. During vaccination, SIV-specific IgG antibodies targeting the envelope were determined in all vaccine groups and in the control group after challenge with SIVmac239. For this assay SIVmac251 infected HSC-F were incubated with heat-inactivated sera from vaccinated and infected animals. SIV-specific antibodies bound to infected T-cells were stained with a FITC-labelled anti-human IgG and determined by flow cytometry. Values are given as mean fluorescence intensities (MFI). Dotted arrows mark points in time of boosts and additional asterisks refer to boosts of group 1 only, whereas the black arrow indicates the point in time of challenge.

Mentions: Hardly any SIV-specific IgG antibodies targeting the env were measured in vaccinated animals during the immunization period (Figure 2). The highest value measured was in monkeys of group 2 at 12 wpi, with a value of 16.0 MFI ± 15.6 (median: 10.9). Upon challenge, SIV-specific IgG antibody levels increased rapidly in monkeys of group 1 (maximum with 99.4 MFI ± 100.4 (median: 51.3)) and 3 (maximum with 80.7 MFI ± 29.8 (median: 85.1)), while those of group 2 were rather low but stable (ranging between 19.2 and 34.8 MFI) between 4 and 28 wpc. As expected, IgG antibody levels increased slowly in control animals. At 2 wpc, env-specific IgGs were significantly lower in controls when compared to immunized monkeys in all groups (p < 0.03); at subsequent points in time (4 and 8 wpc) controls showed minor differences with p-values being attenuated to borderline significance (p = 0.08 and p = 0.06, respectively) and the IgG-titres reached a maximum level of 58.5 MFI ± 39.2 (median: 50.3) at 12 wpc.


Role of complement and antibodies in controlling infection with pathogenic simian immunodeficiency virus (SIV) in macaques vaccinated with replication-deficient viral vectors.

Falkensammer B, Rubner B, Hiltgartner A, Wilflingseder D, Stahl Hennig C, Kuate S, Uberla K, Norley S, Strasak A, Racz P, Stoiber H - Retrovirology (2009)

IgG response to the viral env-proteins. During vaccination, SIV-specific IgG antibodies targeting the envelope were determined in all vaccine groups and in the control group after challenge with SIVmac239. For this assay SIVmac251 infected HSC-F were incubated with heat-inactivated sera from vaccinated and infected animals. SIV-specific antibodies bound to infected T-cells were stained with a FITC-labelled anti-human IgG and determined by flow cytometry. Values are given as mean fluorescence intensities (MFI). Dotted arrows mark points in time of boosts and additional asterisks refer to boosts of group 1 only, whereas the black arrow indicates the point in time of challenge.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2713197&req=5

Figure 2: IgG response to the viral env-proteins. During vaccination, SIV-specific IgG antibodies targeting the envelope were determined in all vaccine groups and in the control group after challenge with SIVmac239. For this assay SIVmac251 infected HSC-F were incubated with heat-inactivated sera from vaccinated and infected animals. SIV-specific antibodies bound to infected T-cells were stained with a FITC-labelled anti-human IgG and determined by flow cytometry. Values are given as mean fluorescence intensities (MFI). Dotted arrows mark points in time of boosts and additional asterisks refer to boosts of group 1 only, whereas the black arrow indicates the point in time of challenge.
Mentions: Hardly any SIV-specific IgG antibodies targeting the env were measured in vaccinated animals during the immunization period (Figure 2). The highest value measured was in monkeys of group 2 at 12 wpi, with a value of 16.0 MFI ± 15.6 (median: 10.9). Upon challenge, SIV-specific IgG antibody levels increased rapidly in monkeys of group 1 (maximum with 99.4 MFI ± 100.4 (median: 51.3)) and 3 (maximum with 80.7 MFI ± 29.8 (median: 85.1)), while those of group 2 were rather low but stable (ranging between 19.2 and 34.8 MFI) between 4 and 28 wpc. As expected, IgG antibody levels increased slowly in control animals. At 2 wpc, env-specific IgGs were significantly lower in controls when compared to immunized monkeys in all groups (p < 0.03); at subsequent points in time (4 and 8 wpc) controls showed minor differences with p-values being attenuated to borderline significance (p = 0.08 and p = 0.06, respectively) and the IgG-titres reached a maximum level of 58.5 MFI ± 39.2 (median: 50.3) at 12 wpc.

Bottom Line: The vaccine was applied via spray-immunization to the tonsils of rhesus macaques and compared with systemic regimens.Independent of the application regimen or route, viral loads were significantly reduced after challenge with SIVmac239 (p < 0.03) compared to controls.In contrast, the amount of the observed complement-mediated lysis did not correlate with the reduction of SIV titres.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Hygiene, Microbiology and Social Medicine, Innsbruck Medical University, 6020 Innsbruck, Austria. barbara.falkensammer@i-med.ac.at

ABSTRACT

Background: We investigated the interplay between complement and antibodies upon priming with single-cycle replicating viral vectors (SCIV) encoding SIV antigens combined with Adeno5-SIV or SCIV pseudotyped with murine leukemia virus envelope boosting strategies. The vaccine was applied via spray-immunization to the tonsils of rhesus macaques and compared with systemic regimens.

Results: Independent of the application regimen or route, viral loads were significantly reduced after challenge with SIVmac239 (p < 0.03) compared to controls. Considerable amounts of neutralizing antibodies were induced in systemic immunized monkeys. Most of the sera harvested during peak viremia exhibited a trend with an inverse correlation between complement C3-deposition on viral particles and plasma viral load within the different vaccination groups. In contrast, the amount of the observed complement-mediated lysis did not correlate with the reduction of SIV titres.

Conclusion: The heterologous prime-boost strategy with replication-deficient viral vectors administered exclusively via the tonsils did not induce any neutralizing antibodies before challenge. However, after challenge, comparable SIV-specific humoral immune responses were observed in all vaccinated animals. Immunization with single cycle immunodeficiency viruses mounts humoral immune responses comparable to live-attenuated immunodeficiency virus vaccines.

Show MeSH
Related in: MedlinePlus