Enhanced CD8+ T cell immune response against a V3 loop multi-epitope polypeptide (TAB13) of HIV-1 Env after priming with purified fusion protein and booster with modified vaccinia virus Ankara (MVA-TAB) recombinant: a comparison of humoral and cellular immune responses with the vaccinia virus Western Reserve (WR) vector

Gómez, Carmen Elena; Rodrı́guez, Dolores; Rodríguez, Juan; Abaitua, Fernando; Duarte, Carlos A.; Esteban, Mariano

doi:10.1016/s0264-410x(01)00389-9

Cited by 25 publications

(19 citation statements)

References 52 publications

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“…We therefore found that in this system not all heterologous prime-boost combinations result in significant CD8 ϩ T cell expansion and that vaccinia vectors have the unusual property of boosting specific CD8 ϩ T cell responses. These observations are consistent with our own previous data and data from various other laboratories working on a variety of systems (3,(25)(26)(27)(28).…”

Section: A Vaccinia Vector Is Capable Of Expanding Memory Cd8 T Cellssupporting

confidence: 93%

“…We do not address this directly here, although a number of previous studies suggest that viral replication may not be crucial for boosting. We have shown that Flu-ME delivered intranasally (allowing it to replicate in the lung epithelium) does not efficiently boost immune responses (14,24), whereas studies comparing the ability of live and attenuated vaccinia to generate responses against HIV epitopes showed that the attenuated virus was in fact the better boosting vector (26,27).…”

Section: Discussionmentioning

confidence: 96%

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Memory CD8+ T Cell Responses Expand When Antigen Presentation Overcomes T Cell Self-Regulation

Cockburn

Chakravarty

Overstreet

et al. 2008

The Journal of Immunology

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Antimicrobial memory CD8+ T cell responses are not readily expanded by either repeated infections or immunizations. This is a major obstacle to the development of T cell vaccines. Prime-boost immunization with heterologous microbes sharing the same CD8+ epitope can induce a large expansion of the CD8+ response; however, different vectors vary greatly in their ability to boost for reasons that are poorly understood. To investigate how efficient memory T cell expansion can occur, we evaluated immune regulatory events and Ag presentation after secondary immunization with strong and weak boosting vectors. We found that dendritic cells were essential for T cell boosting and that Ag presentation by these cells was regulated by cognate memory CD8+ T cells. When weak boosting vectors were used for secondary immunization, pre-established CD8+ T cells were able to effectively curtail Ag presentation, resulting in limited CD8+ T cell expansion. In contrast, a strong boosting vector, vaccinia virus, induced highly efficient Ag presentation that overcame regulation by cognate T cells and induced large numbers of memory CD8+ T cells to expand. Thus, efficient targeting of Ag to dendritic cells in the face of cognate immunity is an important requirement for T cell expansion.

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Section: A Vaccinia Vector Is Capable Of Expanding Memory Cd8 T Cellssupporting

confidence: 93%

Section: Discussionmentioning

confidence: 96%

Memory CD8+ T Cell Responses Expand When Antigen Presentation Overcomes T Cell Self-Regulation

Cockburn

Chakravarty

Overstreet

et al. 2008

The Journal of Immunology

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“…However, this is the first illustration that rFPV can be used to elicit a protective CD8 ϩ T cell response in the malaria model, and that FP9 is more immunogenic than a similar attenuated FPV vaccine strain. Previous studies have shown that attenuated rVVs are more immunogenic delivery systems than their nonattenuated counterparts (36,37). In addition, MVA, which was derived by serial passage from a nonattenuated VV, is reported to elicit more potent T cell responses against the PbCS Ag than the rationally attenuated NY-VAC strain (13).…”

Section: Discussionmentioning

confidence: 99%

Enhanced CD8+ T Cell Immune Responses and Protection Elicited against Plasmodium berghei Malaria by Prime Boost Immunization Regimens Using a Novel Attenuated Fowlpox Virus

Anderson

Hannan

Gilbert

et al. 2004

The Journal of Immunology

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Sterile immunity can be provided against the pre-erythrocytic stages of malaria by IFN-γ-secreting CD8+ T cells that recognize parasite-infected hepatocytes. In this study, we have investigated the use of attenuated fowlpox virus (FPV) strains as recombinant vaccine vectors for eliciting CD8+ T cells against Plasmodium berghei. The gene encoding the P. berghei circumsporozoite (PbCS) protein was inserted into an FPV vaccine strain licensed for use in chickens, Webster’s FPV, and the novel FPV vaccine strain FP9 by homologous recombination. The novel FP9 strain proved more potent as a vaccine for eliciting CD8+ T cell responses against the PbCS Ag. Sequential immunization with rFP9 and recombinant modified vaccinia virus Anakara (MVA) encoding the PbCS protein, administered by clinically acceptable routes, elicited potent CD8+ T cell responses against the PbCS protein. This immunization regimen elicited substantial protection against a stringent liver-stage challenge with P. berghei and was more immunogenic and protective than DNA/MVA prime/boost immunization. However, further improvement was not achieved by sequential (triple) immunization with a DNA vaccine, FP9, and MVA.

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“…Future studies should be implemented with Env immunogens that can elicit cross-clade, neutralizing antibodies (9,49,57,67), and therefore these titers can then be raised by coupling to C3d. In addition, future studies can explore the use of recombinant viral vectors (e.g., modified vaccinia virus Ankara [1,3,21,25,44,45]), adenovirus 5 (15), or alphavirus (13,64), which are being used in many preclinical AIDS vaccine studies. The introduction of C3d fused immunogens into these viral vectors could be a more effective strategy for enhancing immune responses.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of Antibodies to the Human Immunodeficiency Virus Type 1 Envelope by Using the Molecular Adjuvant C3d

Green

Montefiori

Ross

2003

J Virol

116

112

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DNA vaccines expressing the envelope (Env) protein of the human immunodeficiency virus have been relatively ineffective at generating high-titer, long-lasting, neutralizing antibodies in a variety of animal models. In this study, the murine and human homologues of the complement component, C3d, were used in a DNA vaccine to enhance the titers of antibody to Env. Initially, plasmids expressing a secreted form of Env (sgp120) fused to one, two, or three copies of the murine homologue of C3d (mC3d) were constructed. Mice were inoculated with four vaccinations of DNA or two DNA vaccinations, followed by two boosts of affinitypurified gp120 protein. Analyses of titers demonstrated that multiple copies of mC3d coupled to sgp120 induced long-lasting, high-titer anti-Env antibody. Priming mice with sgp120-mC3d-DNA, followed by inoculation of purified gp120 protein, elicited the strongest antibody titers; however, the avidity maturation of the antibody was accelerated in the mice inoculated with sgp120-mC3d 3 -DNA. In addition, DNAs expressing sgp120 fused to three copies of the human homologue of C3d (hC3d 3 ) efficiently enhanced the anti-Env antibody in rabbits. Lastly, antisera from both mice and rabbits vaccinated with DNA expressing sgp120-C3d 3 elicited higher titers of neutralizing antibody than did nonfused forms of Env. These results indicate that C3d, conjugated to sgp120, enhances the antibody responses to Env compared to non-C3d fused forms of Env, and this approach may be one way to overcome the poor ability of DNA vaccines to generate antibodies to Env.

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Cited by 25 publications

References 52 publications

Memory CD8+ T Cell Responses Expand When Antigen Presentation Overcomes T Cell Self-Regulation

Memory CD8+ T Cell Responses Expand When Antigen Presentation Overcomes T Cell Self-Regulation

Enhanced CD8+ T Cell Immune Responses and Protection Elicited against Plasmodium berghei Malaria by Prime Boost Immunization Regimens Using a Novel Attenuated Fowlpox Virus

Enhancement of Antibodies to the Human Immunodeficiency Virus Type 1 Envelope by Using the Molecular Adjuvant C3d

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