Protection against SIV in Rhesus Macaques Using Albumin and CD4-Based Vector-Mediated Gene Transfer

Spitsin, Sergei; Schnepp, Bruce C.; Connell, Mary J.; Liu, Tehui; Dang, Christine M.; Pappa, Vasiliki; Tustin, R. Don; Kinder, Annemarie; Johnson, Philip R.; Douglas, Steven D.

doi:10.1016/j.omtm.2020.04.019

Cited by 4 publications

(7 citation statements)

References 44 publications

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“…In support of this approach, i.m. delivery of AAV-vectored immunoprophylaxis was effective for the suppression of SIV replication in the macaque model 39 . We therefore tested the effectiveness of i.v.…”

Section: Resultsmentioning

confidence: 96%

“…Similarly, in the rhesus macaque SIV model, i.m. administration of AAV vectors expressing broadly neutralizing antibodies suppressed virus loads of SIV, a virus that replicates in secondary lymphoid organs 3,39 . The long-lasting suppression of SIV replication by the vector suggests that transduced terminally differentiated myocytes can produce AAV vector-encoded proteins for a period of several years.…”

Section: Discussionmentioning

confidence: 99%

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Vectored Immunoprophylaxis and Treatment of SARS-CoV-2 Infection

Tada

Dcosta

Minnee

et al. 2023

Preprint

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Vectored immunoprophylaxis was first developed as a means to establish engineered immunity to HIV through the use of an adeno-associated viral vector expressing a broadly neutralizing antibody. We have applied this concept to establish long-term prophylaxis against SARS-CoV-2 by adeno-associated and lentiviral vectors expressing a high affinity ACE2 decoy receptor. Administration of decoy-expressing AAV vectors based on AAV2.retro and AAV6.2 by intranasal instillation or intramuscular injection protected mice against high-titered SARS-CoV-2 infection. AAV and lentiviral vectored immunoprophylaxis was durable and active against recent SARS-CoV-2 Omicron subvariants. The AAV vectors were also effective when administered up to 24 hours post-infection. Vectored immunoprophylaxis could be of value for immunocompromised individuals for whom vaccination is not practical and as a means to rapidly establish protection from infection. Unlike monoclonal antibody therapy, the approach is expected to remain active despite continued evolution viral variants.

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Section: Resultsmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Vectored Immunoprophylaxis and Treatment of SARS-CoV-2 Infection

Tada

Dcosta

Minnee

et al. 2023

Preprint

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“…Rhesus macaques treated with the vector were highly protected against a challenge with SHIV-AD8 and SIVmac239 (Gardner et al, 2015;Spitsin et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…Although the protein neutralized the virus by binding the gp120 subunit of the viral envelope glycoprotein in vitro (Daar et al, 1990; Haim et al, 2009; Orloff et al, 1993; Schenten et al, 1999; Sullivan et al, 1998), it failed to decrease virus loads when used to treat patients. More recently the concept was revived using an adeno-associated virus vector expressing an enhanced soluble eCD4-Ig decoy (Gardner et al, 2015; Spitsin et al, 2020). Rhesus macaques treated with the vector were highly protected against a challenge with SHIV-AD8 and SIVmac239 (Gardner et al, 2015; Spitsin et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Prophylaxis and Treatment of SARS-CoV-2 infection by an ACE2 Receptor Decoy

Tada

Dcosta

Zhou

et al. 2023

Preprint

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The emergence of SARS-CoV-2 variants with highly mutated spike proteins has presented a major obstacle to the use of monoclonal antibodies for the prevention of SARS-CoV-2 infection and treatment of COVID-19. Better prophylactic and therapeutics for current and future variants are needed. We show that a high affinity receptor decoy protein in which a modified ectodomain of human ACE2 is fused a single domain of an immunoglobulin heavy chain Fc region dramatically suppressed virus loads in mice upon challenge with high dose of parental SARS-CoV-2 or Omicron variants BA.1 and BA.2 and potently suppressed virus replication when administered post-infection. The approach offers protection that is broader than monoclonal antibodies that are likely to be evaded by the continued evolution of the viral spike protein.

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