Moderna targets shingles in mRNA pipeline expansion

By Rachel Arthur

- Last updated on GMT

Two of the new vaccine candidates target latent viruses. Pic:getty/artemisdiana
Two of the new vaccine candidates target latent viruses. Pic:getty/artemisdiana

Related tags Moderna mRNA Shingles Vaccine

Moderna is expanding its mRNA pipeline with three new development programs: with vaccine candidates against herpes simplex virus (HSV), varicella-zoster virus (VSV) and a new checkpoint cancer vaccine.

There is no vaccine currently approved against HSV. For shingles, Pfizer is also developing a vaccine​ against the disease, with both mRNA pioneers hoping to offer a vaccine with higher efficacy and a more efficient production process than current vaccines.

Both HSV and VZV are latent viruses that remain in the body for life after infection and can lead to life-long medical conditions. Moderna now has five vaccine candidates against latent viruses in development: with the new targets joining vaccines against cytomegalovirus (CMV), Epstein-Barr virus (EBV), Human immunodeficiency virus (HIV).

Stéphane Bancel, CEO of Moderna, said: "We are committed to addressing latent viruses with the goal of preventing the lifelong medical conditions that they cause with our mRNA vaccine programs.

“With our HSV and VZV vaccine candidates, we also hope to improve the quality of life for those with symptomatic disease.

“With our new checkpoint cancer vaccine, we look forward to exploring if we can induce T cells specific to PD-L1 and IDO1 through vaccination.

“Our research teams are working on additional mRNA candidates, which we look forward to sharing in the future."

The three new projects will build on learnings from the company's COVID-19 vaccine; and join other candidates in Moderna's pipeline which include a flu vaccine, RSV vaccine, and Zika vaccine.

The candidates

Herpes simplex virus vaccine candidate (mRNA-1608)

mRNA-1608 is a vaccine candidate against HSV-2 disease: which primarily infects the genitals. However, Moderna expects that the vaccine could provide cross-protection against HSV-1, which also infects the mouth and face.

Both viruses establish lifelong latent infections within nearby sensory neurons from which they can reactivate and re-infect the skin.

In the US, approximately 18.6 million adults ages 18 to 49 years are living with HSV-2. Globally, approximately 5% of the population in the 18-to-49-year age range is HSV-2 seropositive. 

“There is a significant burden of disease from HSV genital infections,"​ notes Moderna. "Diagnosed​, symptomatic genital herpes causes a reduction in quality of life, which antivirals (current standard of care) only partially restore.

"Moderna expects that an HSV vaccine could deliver similar efficacy as suppressive antiviral treatment and would likely improve compliance and quality of life.”

Varicella-zoster virus vaccine candidate (mRNA-1468)

mRNA-1468 is designed to express varicella-zoster virus (VZV) glycoprotein E (gE) to reduce the rate of shingles (herpes zoster). Shingles occurs in one of three adults in their lifetime and incidence dramatically increases at approximately 50 years of age. Declining immunity in older adults decreases immunity against VZV, allowing reactivation of the virus from latently infected neurons, causing painful and itchy lesions. Moderna has published​ preclinical data on an mRNA vaccine encoding the VZV gE antigen.

VZV causes shingles. Serious herpes zoster complications include postherpetic neuralgia (10-13% of herpes zoster cases), bacterial coinfections, and cranial and peripheral palsies; 1-4% of HZ cases are hospitalized for complications. Severity of disease and likelihood of complications, including postherpetic neuralgia (PHN) also increases with age.

The incidence of herpes zoster has been increasing throughout the world from 0.76 per 1000 person years from 1945 to 1949, to 7.2 per 1000 person years in 2016.

Checkpoint cancer vaccine (mRNA-4359)

mRNA-4359 expresses Indoleamine 2,3​-dioxygenase (IDO) and programmed death-ligand 1 (PD-L1) antigens. Moderna designed mRNA-4359 with the goal of stimulating effector T-cells that target and kill suppressive immune and tumor cells that express target antigens. The company is planning to explore initial indications for advanced or metastatic cutaneous melanoma and non-small cell lung carcinoma (NSCLC).

Melanoma is the fifth most common cancer diagnosis in the US. It accounts for 5.3% of all new cancer diagnoses and 1.5% of all cancer-related deaths.

Cutaneous melanoma is a cancer that starts in the melanocytes (pigment-producing cells) of the skin. If diagnosed at the local stage, the 5-year survival rate is approximately 95%. However, for regional or metastatic disease (stage IIIB+), 5-year survival rates decline to approximately 30 to 60%. Approximately 18,000 new patients are diagnosed with stage IIIB+ cutaneous melanoma in the U.S. Advanced melanoma, a rare and serious type of skin cancer, is responsible for most skin cancer-related deaths, despite representing only 1% of skin cancer cases. Current standard of care pembrolizumab, nivolumab or the combination of nivolumab + ipilimumab.

NSCLC frequently goes undetected, remaining asymptomatic until it has progressed to later stages. Approximately, 115,000 people are diagnosed with metastatic NSCLC or progress to metastatic disease annually in the US.

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