Clover Biopharmaceuticals announced positive Phase I clinical data for its combination respiratory vaccines targeting respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and parainfluenza virus type 3 (PIV3), marking a significant advancement toward addressing critical gaps in respiratory virus protection for older adults.
The biotechnology company reported results from two ongoing Phase I trials evaluating its PreF vaccine candidates using the validated Trimer-Tag platform technology. The studies demonstrate the potential for first-in-class combination vaccines that could both broaden protection beyond RSV and enable effective re-vaccination in previously immunized populations.
Combination Vaccine Trial Shows Strong Multi-Pathogen Response
In the Australian Phase I trial, 144 older adults aged 60-85 years were randomized to receive either SCB-1022 (RSV+hMPV), SCB-1033 (RSV+hMPV+PIV3), or SCB-1019 (RSV alone) as a comparator. The combination vaccines demonstrated robust immune responses across all targeted pathogens at 28 days post-vaccination.
For RSV protection, both combination vaccines achieved geometric mean fold rises (GMFRs) of approximately 6-8 fold in RSV-A and RSV-B neutralizing antibodies, matching the performance of the single RSV vaccine comparator. Importantly, no immune interference was observed from the addition of hMPV and PIV3 antigens.
The hMPV component showed particularly strong responses, with GMFRs of approximately 6-7 fold for hMPV-A and 8-9 fold for hMPV-B neutralizing antibodies in both combination vaccines. For PIV3, SCB-1033 induced approximately 4 fold increases in total PIV3 neutralizing antibodies, with ≥10 fold increases in PIV3 PreF-specific antibodies targeting critical neutralization sites.
"We are pleased to announce positive Phase I clinical data indicating a potential best-in-class profile for our RSV+hMPV±PIV3 combination vaccine candidates," said Joshua Liang, Chief Executive Officer of Clover. "While currently approved protein-based RSV vaccines are safe & effective, critical gaps persist globally, including the inability to prevent significant respiratory disease burden caused by other viruses related to RSV such as human metapneumovirus and parainfluenza virus type 3."
Re-Vaccination Study Demonstrates Superior Immune Boost
The U.S. Phase I re-vaccination trial enrolled older adults who had previously received GSK's AREXVY vaccine at least two seasons prior. An interim analysis of 34 participants revealed that Clover's SCB-1019 heterologous re-vaccination induced 1.6-1.8x higher trends in RSV neutralizing antibody responses compared to homologous AREXVY re-vaccination.
Specifically, SCB-1019 achieved GMFRs of approximately 3.0-3.3 fold in RSV-A and RSV-B neutralizing antibodies, compared to 1.8-1.9 fold for AREXVY re-vaccination. Additionally, 69-75% of participants receiving SCB-1019 showed ≥2-fold increases in RSV neutralizing antibodies, compared to only 33-40% for AREXVY.
These results address a significant clinical need, as AREXVY homologous re-vaccination has previously been reported to boost RSV neutralizing antibodies to only approximately 60-65% of peak levels induced by the initial dose.
Safety Profile Supports Continued Development
Both combination vaccines demonstrated favorable safety and tolerability profiles. Local and systemic adverse events were generally mild and comparable to the single RSV vaccine, which had previously shown significantly better tolerability than AREXVY in separate trials. No vaccine-related serious adverse events, adverse events of special interest, or adverse events leading to discontinuation were observed.
Addressing Unmet Medical Needs
The clinical data addresses two critical gaps in current RSV vaccination strategies. First, existing protein-based RSV vaccines cannot prevent respiratory disease burden from related viruses like hMPV and PIV3. Second, current vaccines show limited effectiveness for re-vaccination when protection wanes over time.
With more than 40% of adults 60 years and older in the U.S. having previously received a protein-based RSV vaccine (approximately 15 million doses), and current clinical data not supporting RSV re-vaccination policy recommendations despite waning efficacy, Clover's combination approach could provide both restored RSV protection and broadened coverage.
Path Forward to Phase II
Based on these positive Phase I results, Clover plans to advance both SCB-1022 and SCB-1033 to Phase II clinical trials in the first half of 2026. Additional data from the ongoing RSV re-vaccination trial is expected by the first half of 2026, which will provide further insights into the potential for heterologous re-vaccination strategies.
The development represents a potential paradigm shift in respiratory virus vaccination, moving from single-pathogen protection to comprehensive coverage of multiple related respiratory viruses while addressing the challenge of waning immunity in previously vaccinated populations.
