Vaccines of the future

April 2, 2024
There is a new era of vaccinology in pharma's pipelines

The turn of the century brought advances in vaccine technology such as recombinant DNA techniques, viral vector platforms and more recently, mRNA.

Armed with new techniques, drugmakers are now able to dream up vaccines for complex diseases like cancer, where traditional methods have sometimes fallen short. 

Cancer vaccines

BioNTech's pancreatic cancer vaccine (autogene cevumeran) 

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, accounting for over 80% of cases diagnosed. Treatment options include surgery, chemotherapy and radiation therapy, but outcomes remain poor.

BioNTech and Genentech have now started a phase 2 trial for their mRNA-based cancer jab for PDAC. This investigational vaccine encodes patient-specific mutations and is being tested with atezolizumab and chemotherapy versus standard chemotherapy.  

The trial will aim to enroll 260 patients worldwide and focus on disease-free survival. The decision follows promising phase 1 results showing a favorable safety profile and potential for delaying cancer recurrence. 

Transgene’s ovarian cancer and HPV-negative head and neck cancers vaccine (TG4050) 
French biotech Transgene is developing a vaccine, using its proprietary myvac platform, in partnership with Japanese telecommunications and technology provider, NEC Corporation, for neoantigen prediction. Transgene's myvac is a viral vector-based immunotherapy platform, targeting solid tumors through individualized treatment. It leverages patient-specific genetic mutations to trigger immune responses against tumors. The vaccine is currently in phase 1 clinical trials.

TG4050 targets ovarian cancer and HPV-negative head and neck cancers, with the goal of inducing specific immune responses against cancer cells. While current treatments include surgery, chemotherapy, radiation, and targeted therapy, outcomes can vary significantly among patients. 

OSE Immunotherapeutics' NSCLC vaccine (Tedopi) 
While non-small cell lung cancer (NSCLC) is the most common type of lung cancer, it has limited treatment options for advanced stages. Treatments include surgery, chemotherapy, radiation therapy, targeted therapy, and immunotherapy. 

Tedopi, currently being developed by French biotech OSE Immunotherapeutics, is a novel T-cell epitope-based cancer vaccine targeting five tumor-associated antigens. It’s the first cancer vaccine demonstrating significant efficacy and improved safety and quality of life in treating advanced NSCLC post-immune checkpoint inhibitor failure compared to standard chemotherapy. 

The vaccine has been granted compassionate use in France, Italy and Spain, and a phase 3 study supported by the FDA and EMA is being prepared to potentially place Tedopi as a second-line treatment for NSCLC patients resistant to immune checkpoint inhibitors. 

Merck and Moderna’s personalized cancer vaccine  (mRNA-4157/V940)
In collaboration with Moderna, Merck is developing a personalized cancer vaccine using mRNA technology. This vaccine approach involves analyzing a patient's specific tumor mutations to create a tailored vaccine intended to stimulate an immune response against the cancer. 

In December 2023, the drugmakers launched a phase 3 trial for V940, alongside Keytruda, targeting adjuvant treatment in non-small cell lung cancer (NSCLC) patients. The INTERPATH-002 trial, already underway in Australia, aims to enroll around 868 patients with completely resected stage II-III NSCLC, comparing the V940 and Keytruda combination against Keytruda alone post-surgery and chemotherapy.  

This effort is part of a broader strategy to explore V940 in various cancers, including an ongoing study in high-risk melanoma. V940 seeks to activate the immune system against cancer’s unique mutations, while Keytruda boosts immune detection and response to tumors.  

The collaboration is the result of a six-year partnership between Moderna and Merck, leveraging their combined expertise in mRNA and immuno-oncology. As Merck exercises its option to jointly develop and commercialize mRNA-4157/V940, both companies will continue to equally share costs and profits globally. 

Flu vaccines

Moderna’s seasonal flu vaccine (mRNA-1010)
Seasonal influenza is a contagious respiratory illness caused by flu viruses, with continued significant annual morbidity and mortality. Current flu vaccines are primarily inactivated or live attenuated vaccines, with varying effectiveness each season.  

Moderna is applying its mRNA technology to develop a more effective and rapidly adaptable flu vaccine. mRNA-1010 has shown promise in phase 3 trials, outperforming GSK's Fluarix in immunogenicity.  

Recently, Blackstone Life Sciences said it will be investing up to $750 million in Moderna's mRNA influenza program. Moderna retains rights to its flu program, with Blackstone receiving milestones and royalties on future flu products. Moderna plans to seek regulatory approval in 2024. 

Pfizer’s quadrivalent flu vaccine (modFlu)
Pfizer’s dug candidate will compete with Moderna’s mRNA-1010, aiming to protect against four flu virus strains each season. The quadrivalent modRNA vaccine candidate will encode the World Health Organization’s recommended strains for the Northern Hemisphere 2022-23 cell culture- or recombinant-based influenza vaccines.  The vaccine is currently in its phase 3 trial, demonstrating efficacy and safety.

Infectious disease vaccines  

Moderna's CMV vaccine (mRNA-1647)
Cytomegalovirus (CMV) is a common virus that can cause serious disease in immunocompromised individuals or in babies if a mother is infected during pregnancy. There are no vaccines currently available for CMV, and treatment includes antiviral medications for those at risk. The virus, which is related to chickenpox, measles and mononucleosis, infects nearly one in three children by age five in the U.S.

In phase 2 trials, RNA-1647 was safe, well-received, and effective in triggering immune responses in participants, regardless of their CMV status, which confirmed the dosing choices for its phase 3 trial. RNA-1647 is an mRNA-based vaccine, composed of six mRNA strands that code for two CMV antigens (glycoprotein B and the pentameric glycoprotein complex), encapsulated within lipid nanoparticles and presented in a freeze-dried form.

Moderna’s Zika virus vaccine (mRNA-1893)
Zika is a virus that spreads through bites from infected Aedes mosquitoes. Infection can lead to microcephaly and other congenital anomalies in infants born to infected mothers, as well as Guillain-Barré syndrome in infected adults. Currently, there are no vaccines or specific antiviral treatments for Zika available. 

mRNA-1893 carries an mRNA sequence that codes for Zika virus structural proteins, prompting cells to produce virus-like particles that simulate the cell's response to an actual infection. The vaccine is in phase 2 trials and has received FDA Fast Track designation. 

Valneva and Pfizer's Lyme Disease vaccine (VLA15)
This vaccine is currently the most advanced candidate for Lyme disease, which caused by the Borrelia burgdorferi bacterium transmitted through tick bites. VLA15 targets the outer surface protein A (OspA) of Borrelia burgdorferi, through a bactericidal-mediated mechanism of action. 

In May of last year, Pfizer and its Paris-based partner Valneva announced a delay in the vaccine's regulatory submission due to issues encountered at a third-party trial site. Months prior, Pfizer had halted the VLA15 vaccine trials for a significant number of U.S. participants, citing potential Good Clinical Practice violations, though not related to the vaccine's safety. 

Despite plans to submit for regulatory approval in 2025, extended enrollment and trial adjustments pushed the timeline. Valneva reported that Pfizer would cover the additional costs, aiming for a 2026 submission pending positive trial outcomes. Pfizer secured commercialization rights from Valneva in a deal up to $308 million during phase 2 trials.

IAVI and Moderna's mRNA HIV vaccine (mRNA-1574, mRNA-1644)
Leveraging mRNA technology similar to that used in COVID-19 vaccines, non-profit IAVI and Moderna are collaborating on an HIV vaccine candidate. Their research is focused on inducing specific types of immune responses believed to be crucial for providing protection against HIV. mRNA-1574 and mRNA-1644 are both in phase 1 stages. 

Previous HIV vaccination candidates have failed. Johnson & Johnson's Janssen discontinued its phase 3 trial of an investigational HIV vaccine, initiated in 2019 and concluding vaccinations in October 2022, due to its ineffectiveness in preventing HIV infection. 

Addiction vaccines

Inimmune’s fentanyl and heroin vaccines
Opioid addiction is a major public health crisis, and current treatments for opioid addiction include medication-assisted therapy (MAT) with drugs like methadone, buprenorphine and naltrexone.  

The University of Montana and Inimmune are collaborating on vaccines aiming to combat opioid addiction and prevent overdoses by targeting opioids such as fentanyl and heroin. The vaccines are currently in preclinical stages with plans for human trials. They work by teaching the immune system to identify and block these drugs, using harmless versions of the opioids called haptens, to stimulate the production of antibodies. These antibodies then capture the real drugs if they enter the body, preventing them from reaching the brain and causing harm. This process effectively reduces the risk of overdose without interfering with other addiction treatments. 

About the Author

Andrea Corona | Senior Editor