NIAID scientists and colleagues are one step closer to developing a safe and effective therapy against alphaviruses with the identification of SKT05, a monoclonal antibody (mAb) derived from macaques vaccinated with virus-like particles (VLPs) representing three encephalitic alphaviruses.

Spread by mosquitos, alphaviruses primarily affect people in one of two ways: causing severe neurological impairment such as encephalitis (brain swelling) or crippling muscle pain similar to arthritis. Western, eastern and Venezuelan equine encephalitis viruses (EEV) are examples of the former, while chikungunya and Ross River viruses are examples of the latter.

Building on studies from the past decade, scientists in NIAID’s Vaccine Research Center and colleagues knew that macaques produce dozens of different protective antibodies when experimentally vaccinated against the EEVs. In a new study published in Cell, the research team identified 109 mAbs in macaques immunized with the experimental western, eastern, and Venezuelan EEV VLP vaccine. All antibodies were individually tested for binding and neutralization against the three EEVs, with the best ones also assessed against arthritogenic alphaviruses not included in the vaccine. Collaborators included scientists from NIAID’s Laboratory of Viral Diseases, USAMRIID’s Virology Division, and Columbia University.

Their work identified SKT05 as the most broadly reactive antibody – remarkably, it also provided protection against both types of alphaviruses, those that cause encephalitis and those that cause arthritic-like disease. High-resolution structural studies further revealed that the way SKT05 binds to alphaviruses could make it resistant to surface changes that can occur in viruses – which means the mAb is likely to have lasting effectiveness.

Further studies are planned to investigate potential clinical development of SKT05. They aim to better define how SKT05 interacts with viruses and whether it can confer protective benefits against additional alphaviruses.

References:
M Sutton et al. Vaccine elicitation and structural basis for antibody protection against alphaviruses. Cell DOI: https://doi.org/10.1016/j.cell.2023.05.019 (2023).

EE Coates, et al. Safety and immunogenicity of a trivalent virus-like particle vaccine against western, eastern, and Venezuelan equine encephalitis viruses: a phase 1, open-label, dose-escalation, randomised clinical trial. Lancet Infectious Diseases (2022).

SY Ko, et al. A virus-like particle vaccine prevents equine encephalitis virus infection in nonhuman primates. Science Translational Medicine (2019).

NIAID-led Work Identifies Bacteria Signaling for Nerve Repair in Mice 

A team of NIAID-led researchers has identified a mechanism in mice in which the immune system and commensal bacteria – microbes that naturally colonize tissues – help repair damaged sensory neurons within the skin. They hope their findings, published in Cell, could lead to therapies that stimulate recovery in people following skin injury and limit damage from chemotherapy and chronic diseases, such as diabetes.

When commensal bacteria colonize the skin, they fine-tune the immune response – known as adaptive immunity – without representing any threat. This study found that when an injury occurs to a colonized surface, say a skin puncture, the preemptive immunity established from the commensal bacteria can help the host recover damaged sensory neurons. That means recovering awareness to touch, temperature, pain and itch.

The mechanism involves a protein, known as interleukin-17A (IL-17A), found in immune cells, and in particular T cells that recognize commensals. When these cells sense an injury, they release IL-17A that is sensed by the damaged nerves and coordinate neuronal repair. Researchers from NIAID’s Laboratory of Host Immunity and Microbiome led the work in collaboration with NIH’s National Institute of Child Health and Human Development and the National Center for Complementary and Integrative Health. Researchers from Harvard Medical School also collaborated.

The findings add to the growing knowledge of how the microbiota – the trillions of beneficial microbes living harmoniously on our skin and inside our gut – bridge biological systems to benefit living beings. The group plans to continue its exploration of exactly how IL-17A communicates with the nervous system to repair damaged tissue and how these findings could lead to novel therapeutic approaches.

Reference:

M. Enamorado et al. Immunity to the microbiota promotes sensory neuron regeneration. Cell. DOI: https://doi.org/10.1016/j.cell.2022.12.037 (2023).