Anti-Chikungunya E1 Protein [Clone CHK-166] — Purified in vivo PLATINUM™ Functional Grade

Clone CHK-166 is most commonly used in vivo in mice to provide protection against chikungunya virus (CHIKV) infection, study the prevention of viral escape and resistance, and assess the efficacy of combination monoclonal antibody therapies.

Key in vivo applications in mice include:

• Prophylactic protection against CHIKV infection: CHK-166, when administered before exposure to CHIKV, can provide complete protection against lethality in highly susceptible mouse models (such as Ifnar^−/− mice), as well as significant reduction in disease in wild-type models.
• Therapeutic administration post-infection: A single dose of CHK-166 given up to 24 hours after infection can protect a majority of mice (~63%) from death.
• Prevention and study of viral resistance: CHK-166 is used to evaluate the emergence of viral escape mutants and resistance. When used in combination with other neutralizing antibodies (e.g., CHK-152), it effectively prevents the development of resistant viral variants and extends the treatment window.
• Combination antibody therapies: CHK-166 is frequently studied alongside other monoclonal antibodies (such as CHK-152) to assess synergistic effects and the potential for enhanced efficacy and reduced resistance.
• Mapping viral epitopes and resistance mutations: CHK-166 is used to generate and characterize CHIKV escape variants, thereby helping to define the functional epitope on the E1 protein and understand mechanisms of immune escape.
• Assessment of viral load and dissemination: Studies typically monitor viremia, tissue viral burden (particularly in joints and muscle), and disease outcomes following CHK-166 treatment in various immunocompetent and immunodeficient mouse models.

Models typically used:

• Ifnar^−/− (type I interferon receptor knockout) mice for robust infection and testing of antibody efficacy.
• C57BL/6 wild-type mice for modeling CHIKV-induced arthritis and other clinical features.

Summary of relevance:
CHK-166 is a well-characterized neutralizing monoclonal antibody targeting the E1 protein of CHIKV. Its main in vivo research utilities in mice are for protection, therapy, resistance studies, and as a component of combination antibody strategies against CHIKV infection.

some of the commonly used antibodies or proteins in combination with CHK-166 in the literature include:

• CHK-152: This is frequently paired with CHK-166 in combination therapy studies to enhance neutralization and prevent viral resistance. Together, they have been shown to be highly effective in reducing viral load and protecting against lethal CHIKV infection in models like mice and rhesus macaques.

• CHK-102 and CHK-263: These antibodies are also used in combination therapies for CHIKV. While CHK-102 often pairs with CHK-152, CHK-263 can be used with CHK-152 as well. These combinations aim to prevent the emergence of viral escape mutants and extend the therapeutic window.

These combinations are integral in the development of effective treatments against Chikungunya virus infections, emphasizing the importance of multi-targeted therapies to combat viral resistance.

Clone CHK-166 is a monoclonal antibody that targets the E1 protein of the chikungunya virus (CHIKV), demonstrating significant therapeutic potential. Here are the key findings from scientific literature regarding CHK-166:

1. Neutralization and Protection: CHK-166 effectively neutralizes CHIKV and protects mice from lethal infection when administered post-infection. It demonstrates strong prophylactic and therapeutic efficacy in animal models.

2. Epitope and Escape Mutants: CHK-166 recognizes amino acids on domain II of the E1 protein, adjacent to the conserved fusion loop. Escape mutants typically feature a K61T mutation in the E1 protein when selected under immune pressure from CHK-166.

3. Combination Therapy: When used in combination with another monoclonal antibody, such as CHK-152, CHK-166 prevents viral resistance and extends the treatment window. This combination also reduces viral spread in rhesus macaques.

4. Mechanism of Action: CHK-166's mechanism involves post-attachment neutralization, suggesting it inhibits the virus after initial attachment to host cells but before the fusion step.

Overall, CHK-166 is a valuable tool in the fight against CHIKV, offering both therapeutic and prophylactic benefits, particularly when used in combination with other antibodies.

Dosing regimens of CHK-166 vary across different mouse models primarily based on several key factors including dose amount, timing of administration, and whether the antibody is used in monotherapy or combination therapy. These variations reflect differences in experimental objectives, mouse strain susceptibility, and the severity of infection being modeled.

Dose Amount Variations

The dose of CHK-166 administered in mouse studies ranges considerably depending on the experimental design. In prophylactic models, doses of 100 µg have been used with complete protective efficacy, where CHK-166 provided 100% survival when administered one day before infection with 10 FFU of CHIKV-LR. However, at lower doses of 10 µg, the prophylactic efficacy of CHK-166 was completely lost (0% survival, 0 of 12 mice). This stark difference demonstrates dose-dependent protection in certain mouse models.

For therapeutic applications, CHK-166 has been administered at 24 hours post-infection, though specific dosing amounts for post-exposure treatment vary. In immunocompromised mice, 50 µg of CHK-166 has been used in combination therapy. More typical dosing ranges from 10–50 µg per mouse, administered a day before viral challenge.

Timing of Administration

The timing of CHK-166 administration significantly impacts outcomes across mouse models. Prophylactic administration typically occurs one day before infection (day −1), which has shown robust protection in several studies. In contrast, post-exposure therapeutic models involve administration at 24 hours post-infection, testing the antibody's ability to control established infection rather than prevent it.

Monotherapy versus Combination Therapy

CHK-166 is frequently used in combination with other neutralizing monoclonal antibodies, particularly CHK-152. When used as combination therapy in Ifnar1^−/−^ mice, 50 µg each of CHK-152 and CHK-166 prevented CHIKV-induced lethality and achieved sterilizing immunity. This combination approach appears particularly important for preventing viral escape, as resistance mutations can emerge during monotherapy. Notably, mice pre-treated with 10 µg of CHK-166 alone did not develop escape mutants in some cases, though resistance with a G64S substitution in E1 was recovered from one animal receiving CHK-166 at 24 hours post-infection.

Mouse Model-Specific Considerations

Different immunocompromised mouse strains require distinct dosing strategies. Studies have utilized Ifnar^−/−^ mice (lacking type I interferon receptors) and Rag1^−/−^ mice (lacking mature B and T cells), with each model presenting different levels of susceptibility to CHIKV infection and potentially requiring adjusted dosing regimens to achieve desired protection levels.