Scientific evidence
A converging body of evidence.
Published studies across experimental models and related human pathway experience support investigation of IFN-α modulation. They are not clinical trials of Vaxiferon®.
Humanized mice — type-I IFN blockade and anti-HIV immunity
Two laboratories · two different antibodies · two distinct mouse models · one convergent conclusion
Cheng L. et al.
NRG humanized mice · anti-IFNAR1
- Reversal of CD4/CD8 hyperactivation
- Lower exhaustion markers (PD-1, TIM-3, TIGIT)
- Restored HIV-specific T-cell responses
- Significant delay of viral rebound after cART interruption
Zhen A. et al.
BLT humanized mice · anti-IFNAR2
- Decreased ISGs (MX1, OAS1, IRF7)
- Lower PD-1 / TIM-3 / CD38
- Restored HIV-specific CD8 function
- Faster viral suppression in combination with ART
Reported conclusionThe biological mechanism underlying the vaccine concept — blocking IFN-α to restore anti-HIV immunity — was reported independently by two laboratories.
Journal of Clinical Investigation · 2017 · Cheng L. et al.; Zhen A. et al.
Humanized mouse models
Two independent laboratories reported findings associated with blockade of type-I interferon signaling in humanized mouse models of HIV infection, including immune-function, exhaustion-marker and reservoir-related measurements. These are published experimental studies, not clinical trials of Vaxiferon®.
Cheng L. et al., J Clin Invest 2017 · Zhen A. et al., J Clin Invest 2017.
SIV-infected rhesus macaques on ART — anti-IFN-α intervention
Human pathway contextAGS-009, an anti-IFN-α antibody, has been evaluated in humans in lupus, with a reported tolerability profile and a known pharmacological profile. It is a different product from Vaxiferon®.
Lymph-node viral DNA
Decreased
Reduced tissue viral measurement
TGF-β and ISG (Mx1)
Decreased
Immunosuppressive signaling reduced
Effector cytokines
Increased
IP-10, IL-15, IL-18, CD8 signatures
Metabolism / erythropoiesis
Increased
After ART interruption, treated animals maintained body weight and erythroid function
Translational significanceThese published animal findings, together with human experience of anti-IFN-α antibodies in another indication, support further investigation of the pathway. They do not establish the safety or efficacy of Vaxiferon®.
JCI Insight · 2022 · Swainson L.A. et al.
Rhesus macaque model and related human pathway experience
Published anti-IFN-α intervention in SIV-infected rhesus macaques on ART reported changes in viral DNA measurements, immune signaling, and metabolic or immune parameters. AGS-009, an anti-IFN-α antibody, has been evaluated in humans in another indication; this provides translational information about targeting the pathway and does not establish the safety or efficacy of Vaxiferon®.
Swainson L.A. et al., JCI Insight 2022 · AGS-009: reported human evaluation in lupus.
Translational progression
Implications for Vaxiferon® development
Published work across models, together with related human pathway experience, forms the rationale for the development programme.
Humanized mice
J Clin Invest · Cheng L. et al.; Zhen A. et al.
Rhesus macaques
JCI Insight · Swainson L.A. et al.
Human pathway experience
Anti-IFN-α antibody evaluated in humans in another indication
Vaxiferon® development
Preclinical development · investigational
ConclusionThe published evidence supports the rationale for future clinical evaluation. Vaxiferon® remains investigational and efficacy has not been established.