These add to a vaccine portfolio that already spans across respiratory viruses and latent viruses, with five candidates in Phase 3 trials, nine in Phase 2 trials, eleven in Phase 1 and eight in pre-clinical development.
mRNA potential against bacterial pathogens
Existing vaccines against bacterial pathogens include live attenuated, subunit protein, and polysaccharide conjugate vaccines.
"Capsular polysaccharide vaccines are widely used and effective for many diseases, but are not always possible or the best choice," notes Moderna - adding that there are also many bacterial pathogens that have no effective vaccines.
"mRNA vaccines offer a potential key advantage to address certain bacteria," says the company. "mRNA vaccines elicit both cellular and humoral responses, which could be advantageous for bacterial pathogens with intracellular and/or extracellular life stages."
There are currently no approved vaccines for Lyme disease: but Moderna’s entry into the market with mRNA-1982 and mRNA-1975 is a response to the growing burden of the disease. It could ultimately see the mRNA pioneer take on Pfizer and Valneva’s candidate (a 6-valent protein subunit vaccine which is currently in Phase 3 trials).
“With approximately 120,000 Lyme disease cases reported per year in the US and Europe, there is a significant quality of life burden created by this pathogen,” notes Moderna.
“With rising atmospheric temperatures, Lyme territory continues to increase in the US. Lyme disease burden follows a bimodal age distribution, affecting mainly children under 15 and older adults. Patients can develop rash, fever, headaches, fatigue, joint pain, swelling, stiffness, and headaches. Older adults appear to have higher odds of unfavorable treatment response as compared with younger patients and neurologic manifestations are more common at presentation for this older adult population."
To address Lyme's biological complexity, Moderna is advancing a seven-valent approach with two Lyme disease vaccine candidates that will be developed in parallel.
"mRNA-1982 is designed to elicit antibodies specific for Borrelia burgdorferi, which causes almost all Lyme disease in the US," explains the company.
"And mRNA-1975 is designed to elicit antibodies specific for the four major Borrelia species causing disease in the US and Europe.”
Tackling vaccine development challenges with norovirus
Another unserved area Moderna identifies is norovirus: with the company announcing development of pentavalent (mRNA-1405) and trivalent (mRNA-1403) candidates for norovirus.
“Enteric viruses, including norovirus, are a leading cause of global acute gastroenteritis (AGE), resulting in significant morbidity and mortality worldwide, particularly among young children and older adults," notes Moderna.
"Norovirus is highly contagious and the leading cause of diarrheal disease globally, associated with 18% of all diarrheal diseases worldwide, resulting in approximately 200,000 deaths per year and substantial healthcare costs.”
Noroviruses are known for their wide genetic and antigenic diversity - with infection from a single strain unlikely to confer broad, long-lasting immunity – and thus creating one of the barriers to norovirus vaccine development to date.
“Given the wide genetic and antigenic diversity of noroviruses, a broadly effective norovirus vaccine will require a multivalent vaccine design," notes Moderna.
Other candidates in this space include Takeda Pharmaceutical spin-out Hillevax’s adjuvanted VLP-based bivalent vaccine (phase 2); Vaxart Pharmaceutical’s oral vaccine (Phase 2); and the tetravalent Longkoma vaccine (Phase 1/2 trials).
Moderna's existing respiratory pipeline includes Phase 3 trials against RSV and influenza, and a next-generation COVID-19 candidate. The pipeline includes four additional influenza vaccines with expanded antigens (Phase 1 - Phase 2), vaccines against other respiratory pathogens (e.g., hMPV, PIV3), and five combination vaccine programs (preclinical - Phase 2).
It is also advancing seven vaccine candidates against five viruses that cause latent infections, five of which are in clinical trials. Moderna's vaccines in this area include candidates against HIV, Epstein-Barr virus, and Cytomegalovirus (CMV).