Deceptive imprinting: a cosmopolitan strategy for complicating vaccination

Nara, Peter L.; Garrity, Robert R.

doi:10.1016/s0264-410x(98)00168-6

Cited by 41 publications

(38 citation statements)

References 64 publications

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“…In these experiments the ESAT-6-based vaccine reduced the lung CFU between 0.37 and 0.50 log 10 , whereas ⌬15ESAT-6 reduced the CFU between 0.66 and 0.84 log 10 . In comparison, BCG reduced the CFU between 0.81 and 1.03 log 10 (Fig. 6A).…”

Section: Subdominant T Cell Responses Promoted By ⌬15esat-6 Efficientmentioning

confidence: 91%

“…We continued by analyzing the sequence of ESAT-6 for the potential presence of subdominant epitopes in addition to the immunodominant ESAT-6 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] . Thirteen groups of CB6F1 mice were each immunized with one of the single peptides derived from ESAT-6 ( Fig.…”

Section: Identification Of Subdominant Epitopes In Esat-6mentioning

confidence: 99%

“…No IFN-␥ release was found in response to the control peptide (ESAT-6 [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] ). In addition to the immunodominant P1 (ESAT-6 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] ) epitope, the analysis of peptides covering the full sequence of ESAT-6 revealed two additional subdominant epitopes to which T cells are not primed during the natural infection. Immunization with both P3 (ESAT-6 [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] ) and P13 (ESAT-6 81-95 ) resulted in dose-dependent recall responses, demonstrating that it is possible to direct a specific response against other epitopes in the ESAT-6 molecule and that the ESAT-6 protein contains additional epitopes that can be processed and recognized by T cells.…”

Section: Identification Of Subdominant Epitopes In Esat-6mentioning

confidence: 99%

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Quality and Vaccine Efficacy of CD4+ T Cell Responses Directed to Dominant and Subdominant Epitopes in ESAT-6 from Mycobacterium tuberculosis

Aagaard

Hoang²,

Vingsbo‐Lundberg³

et al. 2009

The Journal of Immunology

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The ESAT-6 (early secretory antigenic target) molecule is a very important target for T cell recognition during infection with Mycobacterium tuberculosis. Although ESAT-6 contains numerous potential T cell epitopes, the immune response during infection is often focused toward a few immunodominant epitopes. By immunization with individual overlapping synthetic peptides in cationic liposomes (cationic adjuvant formulation, CAF01) we demonstrate that the ESAT-6 molecule contains several subdominant epitopes that are not recognized in H-2d/b mice either during tuberculosis infection or after immunization with ESAT-6/CAF01. Immunization with a truncated ESAT-6 molecule (Δ15ESAT-6) that lacks the immunodominant ESAT-61–15 epitope refocuses the response to include T cells directed to these subdominant epitopes. After aerosol infection of immunized mice, T cells directed to both dominant (ESAT-6-immunized) and subdominant epitopes (Δ15ESAT-6-immunized) proliferate and are recruited to the lung. The vaccine-promoted response consists mainly of double- (TNF-α and IL-2) or triple-positive (IFN-γ, TNF-α, and IL-2) polyfunctional T cells. This polyfunctional quality of the CD4+ T cell response is maintained unchanged even during the later stages of infection, whereas the naturally occurring infection stimulates a response to the ESAT-61–15 epitope that consist almost exclusively of CD4+ effector T cells. ESAT-6 and Δ15ESAT-6 both give significant protection against aerosol challenge with tuberculosis, but the most efficient protection against pulmonary infection is mediated by the subdominant T cell repertoire primed by Δ15ESAT-6.

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Section: Subdominant T Cell Responses Promoted By ⌬15esat-6 Efficientmentioning

confidence: 91%

Section: Identification Of Subdominant Epitopes In Esat-6mentioning

confidence: 99%

Section: Identification Of Subdominant Epitopes In Esat-6mentioning

confidence: 99%

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Quality and Vaccine Efficacy of CD4+ T Cell Responses Directed to Dominant and Subdominant Epitopes in ESAT-6 from Mycobacterium tuberculosis

Aagaard

Hoang²,

Vingsbo‐Lundberg³

et al. 2009

The Journal of Immunology

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“…To date, little work has been carried out by way of exploring structural analogs of neutralization epitopes on carbohydrate moieties of the virus, such as the epitope recognized by 2G12. A sixth category of immunogens employs hyperglycosylation and other mutations to mask non-neutralizing 'decoy' epitopes with the hope that this will redirect the B cell response to key conserved elements of Env [189,190]. Early evidence suggests this approach does indeed refocus the antibody response, but it is not clear whether it will yield an improved response against conserved neutralization epitopes on HIV-1 Env [191,192].…”

mentioning

confidence: 99%

Aiming to induce broadly reactive neutralizing antibody responses with HIV-1 vaccine candidates

Haynes¹,

Montefiori²

2006

Expert Review of Vaccines

103

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Neutralizing antibody induction is a key feature of many effective vaccines and is the only immune response that has proven to be capable of completely blocking AIDS virus infection in animal models. Unfortunately, the extensive genetic variability and complex immune-evasion strategies of HIV-1 have thwarted all attempts to date at eliciting an effective neutralizing antibody response with candidate HIV-1 vaccine immunogens. Recent advances in our understanding of how these evasion strategies operate, coupled with growing progress in unravelling the structure and immunobiology of the viral envelope glycoproteins, are contributing to novel immunogen designs to overcome the many barriers to inducing protective antibodies against HIV-1. Keywordsantiretroviral therapy; HIV-1; host cell fusion; immunogen; neutralizing antibody induction Development of a safe, practical and effective HIV-1 vaccine is one of the highest priorities of the global scientific community [1,2]. Although antiretroviral therapy (ART) has dramatically prolonged the lives of HIV-1 infected patients, ART is not yet routinely available in developing countries, and the global rate of spread of HIV-1 continues unabated. If no effective AIDS vaccine is developed by 2010, the number of people infected world-wide with HIV-1 could exceed 60 million [3].In spite of more than 20 years of research, the types of immune responses needed to protect an immunized individual from HIV-1 infection are not known. Its is known that CD8 + cytotoxic T-cell responses can control HIV-1 replication to varying degrees in acute HIV-1 infection (AHI) [4,5], and when induced by immunogens, can control viral set point after simian immunodeficiancy virus (SIV) or simian HIV (SHIV) challenges in non-human primates [4]. Strong proliferative CD4 + T-cell responses to HIV-1 proteins have been demonstrated to correlate well with immune control of HIV-1 viral load [5]. Therefore, it is highly desirable for an HIV-1 vaccine co induce robust CD4 + and CD8 + T-cell responses in order to control virus replication and reduce the likelihood of subsequent transmission [4][5][6][7]. The potential for complete ('sterilizing') immunity from HIV-1 infection may depend on the presence of pre-existing neutralizing antibodies. We know that neutralizing antibodies can prevent the acquisition of AIDS virus infection after intravenous, vaginal, rectal and oral virus challenge in nonhuman primates [8][9][10][11][12]. This level of protection is highly attractive for a vaccine against a virus, such as HIV-1, which integrates genetically and forms latent viral reservoirs soon after infection. However, the diversity of transmitted HIV-1 genetic variants and the relative resistance of the majority of HIV-1 primary isolates to most types of inducible neutralizing antibodies have posed major hurdles to current vaccine efforts. Furthermore, the few rare broadly reactive neutralizing monoclonal antibodies (mAbs) that have been isolated from HIV-1 infected patients represent species of antibodies that...

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“…Why T cell immunodominance occurs so dramatically for dengue remains mysterious. Most studies suggest that CD8 + T cell receptors (TCRs) specific for dominant epitopes suppress response to other epitopes, due to resource competition, homeostasis, apoptosis, and reduction of viral load [15][16][17]. Immunization with nonstructural proteins is viewed by some as a means to avoid possible antibody dependent enhancement [7].…”

Section: Introductionmentioning

confidence: 99%

Sculpting the immunological response to dengue fever by polytopic vaccination

Zhou

Deem

2006

Vaccine

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The twin challenges of immunodominance and heterologous immunity have hampered discovery of an effective vaccine against all four dengue viruses. Here we explore how the T cell competition and selection underlying these asymmetrical properties impede effective T cell vaccine design. The theory we develop predicts dengue vaccine clinical trial data well. From the insights that we gain by this theory, we propose two new ideas for design of epitope-based T cell vaccines against dengue: polytopic injection and subdominant epitope priming.

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Deceptive imprinting: a cosmopolitan strategy for complicating vaccination

Cited by 41 publications

References 64 publications

Quality and Vaccine Efficacy of CD4+ T Cell Responses Directed to Dominant and Subdominant Epitopes in ESAT-6 from Mycobacterium tuberculosis

Quality and Vaccine Efficacy of CD4+ T Cell Responses Directed to Dominant and Subdominant Epitopes in ESAT-6 from Mycobacterium tuberculosis

Aiming to induce broadly reactive neutralizing antibody responses with HIV-1 vaccine candidates

Sculpting the immunological response to dengue fever by polytopic vaccination

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