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Multiple pharmaceutical companies are investigating the application of mRNA technology to develop vaccines that treat and prevent multiple conditions, from influenza to cancer and beyond.
Moderna, Pfizer, and Boehringer Ingelheim are among the pharmaceutical companies investigating the applicability of mRNA vaccines to treat and prevent other conditions. In addition to a vaccine for HIV, mRNA is being explored as a potential vehicle to create vaccines for several other conditions.1
A messenger RNA (mRNA) influenza vaccine has the potential to improve on the current flu vaccine paradigm. Three mRNA flu vaccines began phase 1 clinical trials in 2020.
Together, Sanofi and Translate Bio are investigating a monovalent flu vac- cine candidate for the hemagglutinin protein of the A/H3N2 strain of the in- fluenza virus.2 When the A/H3N2 strain is most dominant, flu activity may be more severe, particularly among at-risk groups, such as older adults and younger children.
Pfizer’s phase 1 trial (NCT05052697)3 is evaluating the response to their mRNA flu vaccine in a group of healthy adults between 65 and 85 years across the United States. Participants will randomly receive 1 of 4 dose lev- els of the company’s monovalent vaccine candidate (A or B strain of the virus), 1 of 4 dose levels of the bivalent candidate (A and B strains of the virus), the quadrivalent candidate, or a currently approved quadrivalent flu vaccine.
In July 2020, Moderna announced the dosing of the first participants in a phase 1/2 study of mRNA-1010, a quadrivalent flu vaccine candidate4 to eval- uate the safety and immunogenicity of 3 levels of doses of the vaccine targeting hemagglutinin surface proteins from 4 World Health Organization–recom- mended influenza strains. Moderna is also investigating an mRNA candidate (mRNA-1073) combining vaccines for COVID-19 and the flu.5
Respiratory syncytial virus
Previous investigations into a vaccine for respiratory syncytial virus (RSV) have been unsuccessful, with early candidates ultimately strengthening rather than protecting against the disease.6 Currently, no vaccine against RSV exists.
Moderna is now studying mRNA-1345,5 an RSV vaccine candidate that uses the same lipid nanoparticle as their COVID-19 vaccine. In late 2021, the company announced interim data7 from a phase 1 trial (NCT04528719) evaluating the tolerability and reactogenicity of mRNA-1345 in groups of par- ticipants between 18 and 49 years, 65 and 79 years, and 12 and 59 months. Results showed that at 1-month post vaccination, 50-μg and 100-μg doses were “generally well tolerated” in the study’s cohort of younger adults. Moderna expects the study to be completed in 2023.
Moderna’s cytomegalovirus (CMV) vaccine candidate,8 mRNA-1647, combines 6 mRNAs into 1 vaccine aimed at protecting against CMV—a significant unmet need, according to a company press release. CDC estimates suggest 1 in 200 babies are born with CMV, 1 of 5 of whom will experience “devastating sequelae,” such as hearing loss, seizures, and blindness, as well as potential complications later in life.9
The phase 3 CMVictory study (NCT05085366) will evaluate safety and efficacy of mRNA-1647 against primary CMV infection in women between 16 and 40 years. Investigators are aiming to enroll 8000 participants (6900 of childbearing age) across 150 global sites.
In January 2022, Moderna announced10 the dosing of the first candidate in the company’s phase 1 Eclipse study (NCT05164094) of mRNA-1189, an Ep- stein-Barr virus (EBV) vaccine candidate. Although EBV—which causes infec- tious mononucleosis—affects “millions of adolescents globally,” there is no vaccine currently available.
The goal of mRNA-1189 is to prevent EBV-induced infectious mononucleosis and potentially EVB infection itself. The vaccine contains 4 mRNAs that en- code EBV envelope glycoproteins gH, gL, gp42, and gp220.
Cancer vaccines are currently being studied both alone and in combination with chemotherapy and immunotherapy. Some of these vaccines are personalized11—created for individual patients based on their tumor samples—whereas others target the proteins found in cancer cells more globally.1
BioNTech and Regeneron Pharmaceuticals are currently collaborating on an mRNA cancer vaccine for advanced melanoma.12 The vaccine, BNT111, is currently in a phase 2 clinical trial (NCT04526899). In late 2021, BioNTech was granted an FDA fast track designation based on “available preclinical and clinical data showing the potential of BNT111 to overcome current limitations in the treatment of inoperable therapy-resistant advanced-stage melanoma,” according to a press release.12
BioNTech is also collaborating with investigators at the University Medical Center Groningen in the Netherlands in the phase 1 OLIVIA clinical trial (NCT04163094)13 to evaluate the W_ova1 mRNA vaccine in combination with neoadjuvant chemotherapy for ovarian cancer. The first-in-human study is estimated to be completed in late 2023.
Boehringer Ingelheim, CureVac, and Ludwig Cancer Research have joinedforces to study mRNA vaccine BI 1361849 (CV9202), a self-adjuvanting mRNA-based immunotherapeutic cancer vaccine to “mobilize the immune system” to fight tumors.”14 It contains 6 mRNAs coded for 6 different antigens commonly expressed in non–small cell lung cancer (NSCLC).14 It is being investigated in a phase 1/2 clinical trial (NCT03164772)15 as a combination treatment with durvalumab or durvalumab plus tremelimumab for NSCLC.
Moderna is studying at least 3 mRNA vaccines for cancer in clinical trials, 2 of which are personalized. KEYNOTE-942 (NCT03897881) is studying mRNA-4157 as an adjuvant therapy to pembrolizumab in patients with high- risk melanoma.16 KEYNOTE-603 (NCT03313778) is studying the safety, toler- ability, and immunogenicity of mRNA-4157 in patients with solid tumors, both alone in those with resected solid tumors and in combination with pembroli- zumab in those with unresectable solid tumors.17
A third Moderna vaccine—mRNA-5671/V941—is in a phase 1 study (NCT03948763)18 as both a monotherapy and in combination with pembrolizumab to target a specific cancer cell protein found in NSCLC, colorectal cancer, and pancreatic cancer.