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Administration of anti-HIV-1 broadly neutralizing monoclonal antibodies with increased binding affinity to Fcg receptors during acute SHIV infection shapes innate and adaptive cellular immunity [set2]

ABSTRACT: Administration of anti-HIV-1 broadly neutralizing monoclonal antibodies with increased binding affinity to Fcg receptors during acute SHIV infection shapes innate and adaptive cellular immunity [set2]

PROVIDER: PRJNA1072051 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27835700_1.fastq.gz	Fastqsanger.gz
	SRR27835700_2.fastq.gz	Fastqsanger.gz
	SRR27835800_1.fastq.gz	Fastqsanger.gz
	SRR27835800_2.fastq.gz	Fastqsanger.gz
	SRR27835900_1.fastq.gz	Fastqsanger.gz

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Administration of anti-HIV-1 broadly neutralizing monoclonal antibodies with increased binding affinity to Fcg receptors during acute SHIV infection shapes innate and adaptive cellular immunity [set2]

Project description:Anti-HIV-1 broadly neutralizing antibodies (bNAbs) have the dual potential of mediating virus neutralization and antiviral effector functions through their Fab and Fc domains, respectively. So far, bNAbs with enhanced Fc effector functions in vitro have only been tested in NHPs during chronic simian-HIV (SHIV) infection. Here, we investigated the effects of administering in acute SHIVAD8-EO infection either wild-type (WT) bNAbs or bNAbs carrying the S239D/I332E/A330L (DEL) mutation, which increases binding to FcgRs. Emergence of plasma and lymph node (LN) virus was delayed in bNAb-treated monkeys and occurred earlier in monkeys given DEL bNAbs than in those given WT bNAbs, consistent with faster clearance of DEL bNAbs from plasma. DEL bNAb-treated monkeys had higher levels of circulating virus-specific IFNg single-producing and IFNg/MIP-1b double-producing CD8+ CD69+ T cells than the other groups. In LNs, WT bNAbs were evenly distributed between follicular and extrafollicular areas, but DEL bNAbs predominated in the latter. At week 8 post-challenge, LN monocytes and NK cells from DEL bNAb-treated monkeys upregulated proinflammatory signaling pathways and LN T cells downregulated TNF signaling via NF-kB. Overall, bNAbs with increased binding affinity to FcgRs shaped innate and adaptive cellular immunity, which may be important to consider in future strategies of passive bNAb therapy.

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Administration of anti-HIV-1 broadly neutralizing monoclonal antibodies with increased binding affinity to Fcg receptors during acute SHIV infection shapes innate and adaptive cellular immunity

Project description:Administration of anti-HIV-1 broadly neutralizing monoclonal antibodies with increased binding affinity to Fcg receptors during acute SHIV infection shapes innate and adaptive cellular immunity

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Intradermal but not intramuscular MVA immunizations protect against intravaginal tier2 SHIV challenges in macaques

Project description:Route of immunization can markedly influence the quality of immune response. Here, we show that intradermal (ID) but not intramuscular (IM) modified vaccinia Ankara (MVA) vaccinations provide protection from acquisition of intravaginal tier2 SHIV challenges in female macaques. Both routes of vaccination induced comparable levels of serum IgG with neutralizing and non-neutralizing activities. The protection in MVA-ID group correlated positively with serum neutralizing and antibody-dependent phagocytic activities, and envelope-specific vaginal IgA; while the limited protection in MVA-IM group correlated only with serum neutralizing activity. MVA-ID immunizations induced greater germinal center Tfh and B cell responses, reduced the ratio of Th1 to Tfh cells in blood and showed lower activation of intermediate monocytes and inflammasome compared to MVA-IM immunizations. This lower innate activation correlated negatively with induction of Tfh responses. These data demonstrate that the MVA-ID vaccinations protect against intravaginal SHIV challenges by modulating the innate and T helper responses.

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Administration of anti-HIV-1 broadly neutralizing monoclonal antibodies with increased binding affinity to Fcg receptors during acute SHIV infection shapes innate and adaptive cellular immunity

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Project description:It is widely appreciated that effective human vaccines directed against viral pathogens elicit neutralizing antibodies (NAbs). The passive transfer of anti-HIV-1 NAbs conferring sterilizing immunity to macaques has been used to determine the plasma neutralization titers, which must be present at the time of exposure, to prevent acquisition of SIV/HIV chimeric virus (SHIV) infections. We administered five recently isolated potent and broadly acting anti-HIV neutralizing monoclonal antibodies (mAbs) to rhesus macaques and challenged them intrarectally 24 h later with either of two different R5-tropic SHIVs. By combining the results obtained from 60 challenged animals, we determined that the protective neutralization titer in plasma preventing virus infection in 50% of the exposed monkeys was relatively modest (?1:100) and potentially achievable by vaccination.

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