DNA prime-protein boost using subtype consensus Env was effective in eliciting neutralizing antibody responses against subtype BC HIV-1 viruses circulating in China

Zhang, Mingshun; Zhang, Lu; Zhang, Chunhua; Hong, Kui; Shao, Yiming; Huang, Zhibin; Wang, Shixia; Lu, Shan

doi:10.4161/hv.21648

Cited by 7 publications

(7 citation statements)

References 28 publications

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“…However, DNA immunogens usually induce suboptimal humoral responses in humans [230]. Thus, DNA vaccines have been mainly explored in DNA prime-protein boost studies, in which DNA kick-starts both humoral and cellular responses that are then boosted by protein-based immunogens to induce higher titre Ab responses [149,[232][233][234][235][236]. Other immunization experiments have used DNA and protein co-immunization mixtures to increase the durability of humoral responses [237][238][239].…”

Section: Non-viral Vectored Genetic Vaccinesmentioning

confidence: 99%

Strategies for inducing effective neutralizing antibody responses against HIV-1

Moral-Sánchez

Sliepen

2019

Expert Review of Vaccines

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Introduction: Despite intensive research efforts, there is still no effective prophylactic vaccine available against HIV-1. Currently, substantial efforts are devoted to the development of vaccines aimed at inducing broadly neutralizing antibodies (bNAbs), which are capable of neutralizing most HIV-1 strains. All bNAbs target the HIV-1 envelope glycoprotein (Env), but Env immunizations usually only induce neutralizing antibodies (NAbs) against the sequence-matched virus and not against other strains. Areas covered: We describe the different strategies that have been explored to improve the breadth and potency of anti-HIV-1 NAb responses. The discussed strategies include the application of engineered Env immunogens, optimization of (bNAb) epitopes, different cocktail and sequential vaccination strategies, nanoparticles and nucleic acid-based vaccines. Expert opinion: A combination of the strategies described in this review and future approaches are probably needed to develop an effective HIV-1 vaccine that can induce broad, potent and long-lasting NAb responses.

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Section: Non-viral Vectored Genetic Vaccinesmentioning

confidence: 99%

Strategies for inducing effective neutralizing antibody responses against HIV-1

Moral-Sánchez

Sliepen

2019

Expert Review of Vaccines

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“…Although in vivo EP has been utilized to improve immune responses to DNA vaccines alone or in prime-boost regimens with both proteins and viral-vectored vaccines against HIV-1 [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][31][32][33][34][35][36][37], to our knowledge no studies on the effect of in vivo EP on immunogenicity against HIV-1 elicited by DNA-VLP prime-boost immunizations have been reported. Therefore, in the present study we tested the effect of in vivo EP during DNA priming on immunogenicity in the heterologous DNA-VLP prime-boost immunization, in which HIV-1 VLP was produced by a stably transfected Drosophila S2 cell clone as we described before [40].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, it is better to test rabbit and monkey immune serum samples against this global panel. Finally, by using competitive inhibition assay Zhang et al showed that neutralization activity against BC recombinants elicited by in vivo EP in the DNAprotein prime-boost regimen is mediated by CD4BS antibodies [26]. Thus it is interesting to determine what neutralization epitopes are recognized by DDVV + EP sera.…”

Section: Discussionmentioning

confidence: 99%

“…Vasan et al tested ADVAX, a multigenic HIV-1 DNA vaccine candidate, with or without in vivo EP in healthy human volunteers and demonstrated that in vivo EP is safe, tolerable and effective in improving the breadth, potency and durability of cellular immune responses to a DNA vaccine [36]. In heterologous DNA-protein prime-boost regimens both Muthumani et al [25] and Zhang et al [26] demonstrated that in small animal models in vivo EP induced significantly higher antibody binding titers that neutralized several tier 1 viruses [25] or BC recombinant envelopepseudotyped viruses [26]. In heterologous DNA-viral vector prime-boost regimens Winstone et al showed that in vivo EP of a mixture of DNA vaccines encoding multiple SIV antigens in conjunction with IL-12, followed by boosting with a recombinant Ad5-based vaccine expressing SIV antigens led to partial protection from a repeat low dose mucosal SIVmac239 challenge with strong virus set point control in the majority of animals [31].…”

Section: Introductionmentioning

confidence: 99%

“…Thus, collectively these studies demonstrated that in vivo EP induces a transient state of membrane permeability to facilitate uptake of DNA plasmid in the surrounding interstitial spaces and recruits large number of immune cells to the site of immunization [38,39]. Surprisingly, although in vivo EP has been utilized to DNA vaccines alone or in prime-boost regimens with both proteins and viral-vectored vaccines [25][26][27][28][29][31][32][33][34][35][36][37], to our knowledge no studies on the effect of in vivo EP on immunogenicity against HIV-1 elicited by DNA-virus-like particles (VLP) prime-boost regimens have been reported.…”

Section: Introductionmentioning

confidence: 99%

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In vivo electroporation in DNA-VLP prime-boost preferentially enhances HIV-1 envelope-specific IgG2a, neutralizing antibody and CD8 T cell responses

Huang

Zhu

Huang

et al. 2017

Vaccine

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Although in vivo electroporation (EP) has been utilized to improve immunogenicity in DNA vaccines alone or in prime-boost regimens with both proteins and viral-vectors, no studies on in vivo EP in DNA-VLP prime-boost regimens against HIV-1 have been reported. Previously we developed stably transfected Drosophila S2 clones to produce HIV-1 virus-like particles (VLP) and demonstrated that priming mice twice with DNA plasmids encoding HIV-1 gp120 and gag and boosting twice with HIV-1 VLP (i.e. DDVV immunization) elicited both envelope-specific antibody and envelope and gag-specific CD8 T cell responses. However, the potency and the breadth of immunogenicity still need to be improved. In this study we tested the effect of in vivo EP during DNA priming on immunogenicity of this DNA-VLP prime-boost regimen. Here we report that although both DDVV and DDVV+EP elicited gp120-specific ELISA-binding antibody responses, average EC values of gp120-specific ELISA-binding total IgG, IgG2a, but not IgG1, antibody responses were significantly higher in DDVV+EP than in DDVV. Moreover, while DDVV elicited neutralizing antibody responses against autologous, but not other five, strains tested, DDVV+EP not only elicited significantly higher anti-autologous neutralizing antibody responses, but also cross-neutralizes four of five other HIV-1 strains tested, including two tier 2 strains. Finally, although CD4 and CD8 T cells from both DDVV and DDVV+EP immunizations secreted IFN-γ, IL-2, TNF-α upon HIV-1 envelope peptide stimulation, average HIV-1 envelope-specific CD8 T cells that secreted IFN-γ, IL-2 and/or TNF-α were significantly higher in DDVV+EP than in DDVV. Thus we conclude that DDVV+EP immunization preferentially increases HIV-1 envelope-specific T1 cytokine-mediated IgG2a responses and significantly enhances the potency and the breadth of neutralizing antibody responses including tier 2 viruses. Further study on this heterologous regimen in large animals is warranted.

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Co‐delivery of a trimeric spike DNA and protein vaccine with aluminum hydroxide enhanced Th1‐dominant humoral and cellular immunity against SARS‐CoV‐2

Liao,

Huang,

Chiu

et al. 2023

Journal of Medical Virology

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Protein subunit vaccines have been used as prophylactic vaccines for a long time. The well‐established properties of these vaccines make them the first choice for the coronavirus disease 2019 (COVID‐19) outbreak. However, it is not easy to develop a protein vaccine that induces cytotoxic T lymphocyte responses and requires a longer time for manufacturing, which limits the usage of this vaccine type. Here, we report the combination of a recombinant spike (S)‐trimer protein with a DNA vaccine‐encoded S protein as a novel COVID‐19 vaccine. The recombinant S protein was formulated with different adjuvants and mixed with the DNA plasmid before injection. We found that the recombinant S protein formulated with the adjuvant aluminum hydroxide and mixed with the DNA plasmid could enhance antigen‐specific antibody titers, neutralizing antibody titers. We further evaluated the IgG2a/IgG1 isotype and cytokine profiles of the specific boosted T‐cell response, which indicated that the combined vaccine induced a T‐helper 1 cell‐biased immune response. Immunized hamsters were challenged with severe acute respiratory syndrome coronavirus 2, and the body weight of the hamsters that received the recombinant S protein with aluminum hydroxide and/or the DNA plasmid was not reduced. Alternatively, those that received control or only the DNA plasmid immunization were reduced. Interestingly, after the third day of the viral load in the lungs, the viral challenge could not be detected in hamsters immunized with the recombinant S protein in aluminum hydroxide mixed with DNA (tissue culture infectious dose < 10). The viral load in the lungs was 109, 106, and 107 for the phosphate‐buffered saline, protein in aluminum hydroxide, and DNA‐only immunizations, respectively. These results indicated that antiviral mechanisms neutralizing antibodies play important roles. Furthermore, we found that the combination of protein and DNA vaccination could induce relatively strong CD8+ T‐cell responses. In summary, the protein subunit vaccine combined with a DNA vaccine could induce strong CD8+ T‐cell responses to increase antiviral immunity for disease control.

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DNA prime-protein boost using subtype consensus Env was effective in eliciting neutralizing antibody responses against subtype BC HIV-1 viruses circulating in China

Cited by 7 publications

References 28 publications

Strategies for inducing effective neutralizing antibody responses against HIV-1

Strategies for inducing effective neutralizing antibody responses against HIV-1

In vivo electroporation in DNA-VLP prime-boost preferentially enhances HIV-1 envelope-specific IgG2a, neutralizing antibody and CD8 T cell responses

Co‐delivery of a trimeric spike DNA and protein vaccine with aluminum hydroxide enhanced Th1‐dominant humoral and cellular immunity against SARS‐CoV‐2

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