Effect of Passive Administration of Monoclonal Antibodies Recognizing Simian Immunodeficiency Virus (SIV) V2 in CH59-Like Coil/Helical or β-Sheet Conformations on Time of SIV
            <sub>mac251</sub>
            Acquisition

Stamos, James D.; Rahman, Mohammad Arif; Gorini, Giacomo; Castro, Isabela Silva de; Becerra-Flores, Manuel; Wazer, David J. Van; N’guessan, Kombo F.; Clark, Natasha M; Bissa, Massimiliano; Gutowska, Anna; Mason, Rosemarie D.; Kim, Jiae; Rao, Mangala; Paquin‐Proulx, Dominic; Evans, David T.; Cicala, Claudia; Arthos, James; Kwong, Peter D.; Zhou, Tongqing; Cardozo, Timothy; Franchini, Genoveffa

doi:10.1128/jvi.01864-22

Cited by 3 publications

(1 citation statement)

References 41 publications

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“…Interestingly, a lesser decrease than with NCI05 Fab' was observed using NCI09 Fab' (p = 0.089; Figure 4c). The mAbs NCI05 and NCI09, respectively, target the V2 coilhelical and b-sheet conformations, and the passive transfer of NCI05 but not NCI09 is able to delay SIV mac251 acquisition [40]. and vaccinated+IGF-1 (n = 12) animals in week 14.…”

Section: Igf-1 Treatment Reduces V2-specific Adcc and Transiently Inc...mentioning

confidence: 99%

In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4+ T-Cells

Bissa,

Galli,

Schifanella

et al. 2023

Vaccines

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At the heart of the DNA/ALVAC/gp120/alum vaccine’s efficacy in the absence of neutralizing antibodies is a delicate balance of pro- and anti-inflammatory immune responses that effectively decreases the risk of SIVmac251 acquisition in macaques. Vaccine efficacy is linked to antibodies recognizing the V2 helical conformation, DC-10 tolerogenic dendritic cells eliciting the clearance of apoptotic cells via efferocytosis, and CCR5 downregulation on vaccine-induced gut homing CD4+ cells. RAS activation is also linked to vaccine efficacy, which prompted the testing of IGF-1, a potent inducer of RAS activation with vaccination. We found that IGF-1 changed the hierarchy of V1/V2 epitope recognition and decreased both ADCC specific for helical V2 and efferocytosis. Remarkably, IGF-1 also reduced the expression of CCR5 on vaccine-induced CD4+ gut-homing T-cells, compensating for its negative effect on ADCC and efferocytosis and resulting in equivalent vaccine efficacy (71% with IGF-1 and 69% without).

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Section: Igf-1 Treatment Reduces V2-specific Adcc and Transiently Inc...mentioning

confidence: 99%

In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4+ T-Cells

Bissa,

Galli,

Schifanella

et al. 2023

Vaccines

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Loss of HIV candidate vaccine efficacy in male macaques by mucosal nanoparticle immunization rescued by V2-specific response

Rahman,

Bissa,

Scinto

et al. 2024

Nat Commun

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Systemic vaccination of macaques with V1-deleted (ΔV1) envelope immunogens reduce the risk of SIVmac251 acquisition by approximately 60%, with protective roles played by V2-specific ADCC and envelope-specific mucosal IL-17+NKp44+ innate lymphoid cells (ILCs). We investigated whether increased mucosal responses to V2 benefit vaccine efficacy by delivering oral nanoparticles (NPs) that release V2-scaffolded on Typhoid Toxin B (TTB) to the large intestine. Strikingly, mucosal immunization of male macaques abrogated vaccine efficacy with control TTB or empty NPs, but vaccine efficacy of up to 47.6% was preserved with V2-TTB NPs. The deleterious effects of NPs were linked to preferential recruitment of mucosal plasmacytoid dendritic cells (pDCs), reduction of protective mucosal NKp44+ ILCs, increased non-protective mucosal PMA/Ionomycin-induced IFN-γ+NKG2A-NKp44-ILCs, and increased levels of mucosal activated Ki67+CD4+ T cells, a potential target for virus infection. V2-TTB NP mucosal boosting rescued vaccine efficacy, likely via high avidity V2-specific antibodies mediating ADCC, and higher frequencies of mucosal NKp44+ ILCs and of ∆V1gp120 binding antibody-secreting B cells in the rectal mucosa. These findings emphasize the central role of systemic immunization and mucosal V2-specific antibodies in the protection afforded by ΔV1 envelope immunogens and encourage careful evaluation of vaccine delivery platforms to avoid inducing immune responses favorable to HIV transmission.

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Cholera toxin B scaffolded, focused SIV V2 epitope elicits antibodies that influence the risk of SIVmac251 acquisition in macaques

et al. 2023

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IntroductionAn efficacious HIV vaccine will need to elicit a complex package of innate, humoral, and cellular immune responses. This complex package of responses to vaccine candidates has been studied and yielded important results, yet it has been a recurring challenge to determine the magnitude and protective effect of specific in vivo immune responses in isolation. We therefore designed a single, viral-spike-apical, epitope-focused V2 loop immunogen to reveal individual vaccine-elicited immune factors that contribute to protection against HIV/SIV.MethodWe generated a novel vaccine by incorporating the V2 loop B-cell epitope in the cholera toxin B (CTB) scaffold and compared two new immunization regimens to a historically protective ‘standard’ vaccine regimen (SVR) consisting of 2xDNA prime boosted with 2xALVAC-SIV and 1xΔV1gp120. We immunized a cohort of macaques with 5xCTB-V2c vaccine+alum intramuscularly simultaneously with topical intrarectal vaccination of CTB-V2c vaccine without alum (5xCTB-V2/alum). In a second group, we tested a modified version of the SVR consisting of 2xDNA prime and boosted with 1xALVAC-SIV and 2xALVAC-SIV+CTB-V2/alum, (DA/CTB-V2c/alum).ResultsIn the absence of any other anti-viral antibodies, V2c epitope was highly immunogenic when incorporated in the CTB scaffold and generated highly functional anti-V2c antibodies in the vaccinated animals. 5xCTB-V2c/alum vaccination mediated non-neutralizing ADCC activity and efferocytosis, but produced low avidity, trogocytosis, and no neutralization of tier 1 virus. Furthermore, DA/CTB-V2c/alum vaccination also generated lower total ADCC activity, avidity, and neutralization compared to the SVR. These data suggest that the ΔV1gp120 boost in the SVR yielded more favorable immune responses than its CTB-V2c counterpart. Vaccination with the SVR generates CCR5- α4β7+CD4+ Th1, Th2, and Th17 cells, which are less likely to be infected by SIV/HIV and likely contributed to the protection afforded in this regimen. The 5xCTB-V2c/alum regimen likewise elicited higher circulating CCR5- α4β7+ CD4+ T cells and mucosal α4β7+ CD4+ T cells compared to the DA/CTB-V2c/alum regimen, whereas the first cell type was associated with reduced risk of viral acquisition.ConclusionTaken together, these data suggest that individual viral spike B-cell epitopes can be highly immunogenic and functional as isolated immunogens, although they might not be sufficient on their own to provide full protection against HIV/SIV infection.

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Effect of Passive Administration of Monoclonal Antibodies Recognizing Simian Immunodeficiency Virus (SIV) V2 in CH59-Like Coil/Helical or β-Sheet Conformations on Time of SIV _mac251 Acquisition

Cited by 3 publications

References 41 publications

In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4+ T-Cells

In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4+ T-Cells

Loss of HIV candidate vaccine efficacy in male macaques by mucosal nanoparticle immunization rescued by V2-specific response

Cholera toxin B scaffolded, focused SIV V2 epitope elicits antibodies that influence the risk of SIVmac251 acquisition in macaques

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Effect of Passive Administration of Monoclonal Antibodies Recognizing Simian Immunodeficiency Virus (SIV) V2 in CH59-Like Coil/Helical or β-Sheet Conformations on Time of SIV mac251 Acquisition

Cited by 3 publications

References 41 publications

In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4+ T-Cells

In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4+ T-Cells

Loss of HIV candidate vaccine efficacy in male macaques by mucosal nanoparticle immunization rescued by V2-specific response

Cholera toxin B scaffolded, focused SIV V2 epitope elicits antibodies that influence the risk of SIVmac251 acquisition in macaques

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Product

Resources

About

Effect of Passive Administration of Monoclonal Antibodies Recognizing Simian Immunodeficiency Virus (SIV) V2 in CH59-Like Coil/Helical or β-Sheet Conformations on Time of SIV _mac251 Acquisition