Moderna Unveils Results of New mRNA Vaccine Candidate Trials

The pharmaceutical powerhouse Moderna has made headlines over the past year by creating an effective vaccine for the novel coronavirus that employs messenger RNA (mRNA) technology. As the Covid-19 pandemic rages on and demand for the 2-dose vaccine remains high, the biotechnology company is deploying mRNA for use in new vaccines that hopefully will provide immunity against diseases such as respiratory syncytial virus (RSV), cytomegalovirus (CMV), human immunodeficiency virus (HIV), Zika, Epstein-Barr Virus, and influenza, among others.

Riding on the success of the company’s COVID-19 vaccine, Moderna has 14 different mRNA-based vaccines currently undergoing clinical trials. The firm recently hosted its second annual Vaccines Day, during which it held presentations demonstrating the potential of mRNA technology to vanquish a number of viruses that have so far eluded the efforts of the scientific community.

The RSV vaccine currently being trialed encodes for the F glycoprotein stabilized in the prefusion conformation, which enables a better neutralizing antibody response than it would in a postfusion state. Phase 1 interim data revealed that the vaccine boosted RSV neutralizing antibodies in adults aged 18 to 49 who were seropositive for the virus.

One month after a single vaccination with either 50 ug or 100 ug of vaccine, subjects experienced a geometric mean fold rise in neutralizing antibodies of at least 20.5 for RSV-A and at least 11.7 for RSV-B. This is considerably higher than the 2.7 geometric mean fold rise in neutralizing antibodies to RSV-A after 1 month that Moderna’s previous RSV vaccine candidate elicited.

Moderna plans to examine the possibility of combining its current RSV vaccine candidate with its vaccines used to fight respiratory illnesses in children and adults separately. RSV is extremely common and typically causes no serious symptoms, but in very young children and older adults with chronic conditions, it can lead to pneumonia. Although there are several candidates, there is no RSV vaccine approved for commercial use at this time.

CMV is another virus that Moderna hopes to eradicate. Each vial of the CMV vaccine being tested contains 6 mRNAs designed to encode for the pentamer and glycoprotein B on the virus, both of which play a role in infection. The new vaccine helps the body mount a response to both the pentamer and glycoprotein B.

Interim 7-month data from the phase 2 study reveals the vaccine’s promise: In subjects who were seronegative for CMV, neutralizing antibody geometric mean titers (GMT) against epithelial cell infection were a minimum of 20-fold higher after the third vaccination than at baseline, while neutralizing antibody GMTs against fibroblast infection were roughly the same as at baseline. In subjects who tested positive for CMV, neutralizing antibody GMTs against epithelial cell infection were at least 6.8-fold higher after than third vaccination than at baseline, while neutralizing antibody GMTs against fibroblast infection were roughly 2-fold higher.

Subjects in the phase 2 trial were given vaccines in 50 ug, 100 ug, and 150 ug doses. Based on the results, the phase 3 trial will zero in on the 100 ug dose, to be given to seronegative women between ages 16 and 40.

While CMV is common and normally doesn’t cause complications, it can occasionally impact the liver, brain, lungs, and spleen. In babies, the most common complication is hearing loss.

Scientists have been working toward an HIV cure for decades, although a vaccine has so far proven elusive. Working with the International AIDS Vaccine Initiative (IAVI) and Scripps Research, Moderna has created an HIV vaccine that uses mRNA technology in an effort to generate broadly neutralizing HIV-1 antibodies, or bNAbs, that act against the virus. Results from a phase 1 trial show that the desired response occurred in 97% of participants who received the vaccine.

In addition to RSV, CMV, and HIV, Moderna is aiming to leverage its mRNA technology to focus on creating vaccines for diseases such as Zika, malaria, influenza, and hepatitis C. There are no commercially available vaccines for the great majority of human viruses.