Moderna announces three new mRNA vaccine candidates. And one could cancel cancer

As the mRNA vaccines against COVID-19 and its variants proved efficient, Moderna, a biotechnology company working on messenger RNA (mRNA) therapeutics and vaccines, announced that it is expanding its mRNA pipeline with three new development programs, in a press release. 

Among the three programs are mRNA-1608, a candidate against Herpes simplex virus (HSV), mRNA-1468, a candidate against varicella-zoster virus (VZV) to reduce the rate of herpes zoster (shingles), and mRNA-4359, a new checkpoint cancer vaccine.

The new programs are a sign of Moderna's commitment to expanding its mRNA portfolio, after the company’s experience with its COVID-19 vaccine Spikevax.

The vaccine candidates, mRNA-1608 and mRNA 1468 are against HSV and VZV respectively, which are latent viruses that remain in the body for life after infection and can lead to life-long medical conditions. 

Moderna's HSV vaccine candidate, mRNA-1608, is to target HSV-2 disease, with an expectation of providing cross-protection against HSV-1. mRNA-1608 aims to induce a strong antibody response with neutralizing and effector functionality combined with cell-mediated immunity. There is no vaccine approved against HSV yet.

Herpes simplex viruses (commonly known as herpes) are categorized into two types: HSV-1 infects the mouth, face, and genitals, and HSV-2 primarily infects the genitals. Both viruses establish lifelong latent infections within nearby sensory neurons from which they can reactivate and re-infect the skin. In the U.S., approximately 18.6 million adults ages 18 to 49 years are living with HSV-2. Approximately 5 percent of the world population in the 18-to-49-year age range is HSV-2 seropositive. 

Moderna's VZV vaccine candidate (mRNA-1468) is designed to express VZV glycoprotein E (gE) to reduce the rate of shingles (herpes zoster). Serious herpes zoster complications include postherpetic neuralgia (10-13 percent of herpes zoster cases), bacterial coinfections, and cranial and peripheral palsies; 1-4 percent of HZ cases are hospitalized for complications. The severity of disease and likelihood of complications, including postherpetic neuralgia (PHN), also increases with age.

The number of cases of herpes zoster has been increasing throughout the world; from 1945 to 1949, the ratio was 0.76 per 1000 people, while it was 7.2 per 1000 person in 2016, according to a study published in the US National Library of Medicine.

Moderna's cancer vaccine candidate (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, and 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 in the U.S. It accounts for 5.3 percent of all new cancer diagnoses and 1.5 percent of all cancer-related deaths. 

However, 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 U.S. 

Five mRNA vaccine candidates

The company currently has five vaccine candidates against latent viruses in development, including against cytomegalovirus (CMV), Epstein-Barr virus (EBV), Human immunodeficiency virus (HIV), HSV and VZV.

"We are pleased to announce these new development programs, which reflect the continued productivity of our platform and the potential of our mRNA technology to impact the lives of hundreds of millions of people," said Stéphane Bancel, Chief Executive Officer of Moderna.
"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," he added.