An HIV Vaccine — Evolving Concepts

Johnston, Margaret I.; Fauci, Anthony S.

doi:10.1056/nejmra066267

Cited by 234 publications

(203 citation statements)

References 53 publications

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“…This failure highlights the challenges facing HIV-1 vaccine development, which calls for new systematic approaches, including novel antigen design, new vaccine vectors, and novel adjuvants [1,2,41]. Members of the poxvirus family, especially attenuated poxviruses, like modified vaccinia virus Ankara (MVA), NYVAC, and ALVAC, have been used as vectors for HIV-1 vaccines.…”

Section: Discussionmentioning

confidence: 99%

“…Safe and effective vaccines are desperately needed to contain the spread of Human Immunodeficiency Virus Type 1 (HIV-1), which continues to spread globally [1,2]. Members of the poxvirus family (poxviridae) have, in recent years, received considerable attention for the development of vaccine vectors that can induce humoral and cellular immunity against virus infections as well as immunotherapy for cancer [3].…”

Section: Introductionmentioning

confidence: 99%

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CD40L expressed from the canarypox vector, ALVAC, can boost immunogenicity of HIV-1 canarypox vaccine in mice and enhance the in vitro expansion of viral specific CD8+ T cell memory responses from HIV-1-infected and HIV-1-uninfected individuals

Liu

Stone

et al. 2008

Vaccine

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SummaryHuman immunodeficiency virus-1 (HIV-1) canarypox vaccines are safe but poorly immunogenic. CD40 ligand (CD40L), a member of the tumor necrosis factor superfamily (TNFSF), is a pivotal co-stimulatory molecule for immune responses. To explore whether CD40L can be used as an adjuvant for HIV-1 canarypox vaccine, we constructed recombinant canarypox viruses expressing CD40L. Co-immunization of mice with CD40L expressing canarypox and the canarypox vaccine expressing HIV-1 proteins, vCP1452, augmented HIV-1 specific cytotoxic T lymphocyte (CTL) responses in terms of frequency, polyfunctionality and interleukin (IL)-7 receptor α chain (IL-7Rα, CD127) expression. In addition, CD40L expressed from canarypox virus could significantly augment CD4 + T cell responses against HIV-1 in mice. CD40L expressed from canarypox virus matured human monocyte-derived dendritic cells (MDDCs) in a tumor necrosis factor α (TNF-α) independent manner, which underwent less apoptosis, and could expand ex vivo Epstein-Barr virus (EBV)-specific CTL responses from healthy human individuals and ex vivo HIV-1-specific CTL responses from HIV-1-infected individuals in the presence or absence of CD4 + T cells. Taken together, our results suggest that CD40L incorporation into poxvirus vectors could be used as a strategy to enhance their immunogenicity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CD40L expressed from the canarypox vector, ALVAC, can boost immunogenicity of HIV-1 canarypox vaccine in mice and enhance the in vitro expansion of viral specific CD8+ T cell memory responses from HIV-1-infected and HIV-1-uninfected individuals

Liu

Stone

et al. 2008

Vaccine

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“…[2][3][4][5][6] Ideally, an effective vaccine with the ability to prevent HIV-1 infection would elicit both humoral and cellular immune responses. [7][8][9] Since no candidate immunogen is capable of stimulating broadly neutralizing antibodies, a protective vaccine against HIV-1 infection based solely on the elicitation of protective antibodies is still not viable. 10,11 While non-neutralizing antibodies may effectively protect against HIV-1 infection, correlates of protection have still not been defined.…”

Section: Introductionmentioning

confidence: 99%

In silicodesign of a DNA-based HIV-1 multi-epitope vaccine for Chinese populations

Yang

Sun

Guo

et al. 2015

Human Vaccines & Immunotherapeutics

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“…The most frequently used combination is a DNA prime followed by a viral vector boost; this often results in an increase in the magnitude and durability of the antigen-specific cellular immune response (reviewed in [57]). Consistent with this, a DNA prime, followed by an amplicon boost, results in an increase in the magnitude of the CD8 + T-cell responses to an encoded HIV antigen in mice [58].…”

Section: Discussionmentioning

confidence: 99%

HSV-1 amplicon vectors elicit polyfunctional T cell responses to HIV-1 Env, and strongly boost responses to an adenovirus prime

Duke

Maguire

Keefer

et al. 2007

Vaccine

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HSV-1 amplicon vectors elicit strong T-cell responses to encoded antigens but the qualitative nature of these responses is poorly understood. Antigen-specific CD4 + and CD8 + T-cell responses to amplicon and adenovirus (rAd5) vectors encoding HIV-1 gp120 were assessed following immunization of mice, by performing intracellular cytokine staining for IFNγ, IL-2 and TNFα, following stimulation of splenocytes with a HIV-1 Env peptide pool. The quality of the primary Tcell response to amplicon and rAd5 vectors was strikingly similar, but there were qualitative differences in responses to amplicon vectors that incorporated different promoters upstream of gp120 -suggesting that promoters can significantly influence immune response quality. When prime-boost combinations were studied, a rAd5 prime and amplicon boost elicited the highest T-cell response. Furthermore, protocols that incorporated a rAd5 prime consistently elicited a greater proportion of polyfunctional CD4 + T-cells -regardless of boost. This suggests that initial priming can shape immune response quality after a boost. Overall, these findings provide insight into effective vector combinations for HIV-1 vaccine development.

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An HIV Vaccine — Evolving Concepts

Cited by 234 publications

References 53 publications

CD40L expressed from the canarypox vector, ALVAC, can boost immunogenicity of HIV-1 canarypox vaccine in mice and enhance the in vitro expansion of viral specific CD8+ T cell memory responses from HIV-1-infected and HIV-1-uninfected individuals

CD40L expressed from the canarypox vector, ALVAC, can boost immunogenicity of HIV-1 canarypox vaccine in mice and enhance the in vitro expansion of viral specific CD8+ T cell memory responses from HIV-1-infected and HIV-1-uninfected individuals

In silicodesign of a DNA-based HIV-1 multi-epitope vaccine for Chinese populations

HSV-1 amplicon vectors elicit polyfunctional T cell responses to HIV-1 Env, and strongly boost responses to an adenovirus prime

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