Viruses 2014, 6(8), 3334-3347; doi:10.3390/v6083334
Article

Divergence of Primary Cognate B- and T-Cell Proliferative Responses to Subcutaneous and Intravenous Immunization with Virus-Like Particles

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Received: 28 May 2014; in revised form: 15 August 2014 / Accepted: 18 August 2014 / Published: 22 August 2014
(This article belongs to the Special Issue AIDS Vaccine 2014)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: A major advantage of virus-like particle (VLP) vaccines against HIV is their structural identity to wild-type viruses, ensuring that antigen-specific B-cells encounter the envelope protein in its natural conformation. For the induction of affinity-matured antibodies, the B-cells must also obtain help from T-cells that are restricted by linear epitopes. Using B- and T-cell transgenic mouse models, we compared the efficacy of modified HIV-VLPs delivered by subcutaneous and intravenous immunization to stimulate primary B- and T-cell proliferative responses in different lymphoid organs. VLPs containing an influenza virus hemagglutinin epitope within the HIV-Gag protein induced comparable primary cognate T-cell proliferative responses in the draining lymph node and the spleen, irrespective of the delivery route. In contrast, after subcutaneous immunization with HIV-Gag VLPs containing hen egg lysozyme (HEL) on their surface, the proliferative response of transgenic HEL-specific B-cells was restricted to the draining lymph nodes, while intravenous VLP immunization primarily induced a B-cell proliferative response in the spleen. In vitro co-culture experiments further revealed that the presentation of VLP-associated surface antigens by dendritic cells to cognate B-cells is inefficient. This is consistent with a direct triggering of the B-cell proliferative response by the VLPs and suggests that HIV VLPs may indeed be suitable to directly promote the expansion of B-cells specific for conformational epitopes that are unique to functionally-active Env spikes on the virion. Further investigations are warranted to explore potential differences in the quality and protective potency of HIV-specific antibody responses induced by the two routes.
Keywords: lentiviral VLP; B-cell proliferation; T-cell proliferation
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MDPI and ACS Style

Temchura, V.; Kalinin, S.; Nabi, G.; Tippler, B.; Niezold, T.; Überla, K. Divergence of Primary Cognate B- and T-Cell Proliferative Responses to Subcutaneous and Intravenous Immunization with Virus-Like Particles. Viruses 2014, 6, 3334-3347.

AMA Style

Temchura V, Kalinin S, Nabi G, Tippler B, Niezold T, Überla K. Divergence of Primary Cognate B- and T-Cell Proliferative Responses to Subcutaneous and Intravenous Immunization with Virus-Like Particles. Viruses. 2014; 6(8):3334-3347.

Chicago/Turabian Style

Temchura, Vladimir; Kalinin, Svetlana; Nabi, Ghulam; Tippler, Bettina; Niezold, Thomas; Überla, Klaus. 2014. "Divergence of Primary Cognate B- and T-Cell Proliferative Responses to Subcutaneous and Intravenous Immunization with Virus-Like Particles." Viruses 6, no. 8: 3334-3347.


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