Vaxcyte's VAX-31 Pneumococcal Vaccine Reaches Critical Development Milestones Across Adult and Infant Programs

Vaxcyte, a vaccine innovation company, has announced significant progress in its clinical development programs for VAX-31, an experimental 31-valent pneumococcal conjugate vaccine designed to address a major gap in current pneumococcal protection strategies. The company is executing a comprehensive clinical approach that simultaneously advances late-stage studies in adults while completing enrollment in pediatric trials, positioning the candidate to potentially set new standards in disease prevention across multiple age groups.

The clinical advancement represents a carefully coordinated strategy developed in close consultation with the U.S. Food and Drug Administration (FDA). The company’s multi-pronged approach reflects a deep understanding of real-world vaccination practices and the diverse immunization needs of different patient populations. With preliminary data expected throughout 2026 and 2027, Vaxcyte is progressing toward its goal of submitting a Biologics License Application (BLA) to secure regulatory approval.

Comprehensive Adult Clinical Strategy Takes Shape

The VAX-31 adult development program encompasses three distinct Phase 3 trials that collectively capture the diversity of immunization scenarios clinicians and patients encounter in practice. This multi-trial approach generates a robust safety and efficacy dataset while examining how the vaccine performs across different patient backgrounds and vaccination schedules.

The first active trial, designated OPUS-2, evaluates VAX-31 when administered simultaneously with seasonal influenza vaccination in pneumococcal-naive adults aged 50 and older. Vaxcyte has begun enrolling approximately 1,300 participants across roughly 25 clinical sites throughout the United States. This study design mirrors real-world clinical practice, where patients often receive multiple vaccines during a single visit. The trial employs a randomized, double-blind, placebo-controlled methodology to rigorously assess both the safety profile and immune response generation across all 31 pneumococcal serotypes.

The OPUS-2 protocol includes two distinct participant groups that receive different vaccination sequences. In the concomitant administration group, participants receive a seasonal influenza vaccine and VAX-31 on the same day, with a placebo injection one month later. The sequential administration group receives the influenza vaccine with placebo on day one, followed by VAX-31 administered one month afterward. This design allows researchers to evaluate whether timing of administration affects immune response while maintaining scientific rigor through blinding and control measures. Safety monitoring extends for six months post-vaccination across all participants.

A separate Phase 3 trial, OPUS-3, focuses on adults with prior pneumococcal vaccination history, a clinically important population that represents a substantial portion of the adult vaccination market. Vaxcyte plans to initiate OPUS-3 enrollment in the first quarter of 2026, targeting approximately 720 healthy U.S. adults aged 50 years and older. Participants will be stratified based on their previous pneumococcal vaccination experience, including those vaccinated with Pneumovax®23, Prevnar 20®, or other available pneumococcal vaccines.

The OPUS-3 study design reflects evolving clinical practice, where many older adults have already received at least one pneumococcal vaccine. Participants will be randomized to receive either a single dose of VAX-31 or the active comparator PCV20, with active-controlled methodology providing meaningful context for interpreting the immunogenicity data. Like OPUS-2, safety and tolerability assessments will continue throughout a six-month observation period.

The third trial, OPUS-1, represents the pivotal noninferiority study that directly evaluates VAX-31’s ability to prevent invasive pneumococcal disease and pneumonia in adults. This remains the cornerstone of the adult clinical program and continues to enroll participants. Across all three adult Phase 3 trials, approximately 6,000 total adults are expected to participate, with roughly 3,400 receiving VAX-31 directly. This substantial dataset will support regulatory submissions and provide comprehensive evidence of the vaccine’s performance in diverse clinical scenarios.

Pediatric Development Advances with Completed Enrollment

The VAX-31 infant development program reached a major milestone with the completion of enrollment in its Phase 2 dose-finding study, with more than 900 healthy infants participating. This pediatric trial evaluates VAX-31’s safety, immunogenicity, and optimal dosing strategy compared to the currently available standard-of-care vaccine PCV20.

The infant study design follows a scientifically rigorous schedule, with participants receiving three primary immunization doses at two, four, and six months of age, followed by a booster vaccination at 12 to 15 months. All enrolled infants have now received at least their initial two-month dose, allowing researchers to begin accumulating preliminary immunogenicity data while continuing follow-up observations through the booster phase.

VAX-31 is engineered to substantially expand pneumococcal coverage in infants by adding 11 serotypes beyond those contained in the current standard-of-care vaccine. Preliminary calculations based on surveillance data suggest that this expanded serotype coverage could potentially increase protection against invasive pneumococcal disease from approximately 69% to approximately 92% in U.S. children under five years of age. Similarly, for acute otitis media, the expanded coverage may increase protection from approximately 61% to approximately 96% in this age group.

The scientific rationale for expanded serotype coverage rests on epidemiological evidence showing that certain historically prevalent strains continue to circulate and cause disease in vulnerable populations. By maintaining protection against both current and historically important strains while adding new coverage, VAX-31 aims to reduce disease burden more comprehensively than single-target vaccination strategies.

Expected Data Releases and Regulatory Timeline

Vaxcyte has established a clear timeline for communicating clinical progress to the scientific and regulatory community. In the fourth quarter of 2026, the company expects to announce preliminary safety, tolerability, and immunogenicity data from the OPUS-1 Phase 3 pivotal trial. These initial findings will provide important validation of the vaccine’s core clinical hypothesis regarding disease prevention.

During the first half of 2027, Vaxcyte anticipates releasing topline data from both the OPUS-2 and OPUS-3 Phase 3 adult studies. The same timeframe is expected for preliminary results from the infant Phase 2 dose-finding study, which will include immunogenicity assessments from both the primary three-dose immunization series and the booster dose.

The coordinated release of adult and infant data in early 2027 positions Vaxcyte to compile these findings into a comprehensive BLA submission to the FDA. This regulatory pathway represents a standard approach for vaccine candidates that have completed Phase 3 trials and generated sufficient safety and immunogenicity evidence to support licensure.

Domestic Manufacturing Expansion Strategy

Recognizing that vaccine availability depends critically on reliable manufacturing capacity, Vaxcyte has committed up to $1 billion toward establishing U.S.-based fill-finish manufacturing infrastructure. The company announced plans to build a custom fill-finish production line in North Carolina, an established vaccine development hub with existing expertise and infrastructure.

The company expects to begin buildout of its custom pneumococcal conjugate vaccine fill-finish line in the first quarter of 2026. To support this expansion, Vaxcyte has established a dedicated local presence in North Carolina with full-time employees specializing in chemistry, manufacturing and controls activities. The company is actively recruiting experienced scientific and manufacturing professionals to ensure that facility operations meet the highest standards for vaccine production and quality assurance.

This long-term manufacturing commitment underscores Vaxcyte’s commitment to ensuring adequate vaccine supply once regulatory approval is obtained. For a vaccine addressing a significant public health burden, reliable domestic production capacity represents a critical component of successful product commercialization and patient access.

The Burden of Pneumococcal Disease and Clinical Rationale

Pneumococcal disease, caused by the bacterium Streptococcus pneumoniae, remains a significant public health challenge despite existing vaccine options. The disease manifests in multiple forms, ranging from non-invasive infections such as pneumonia, otitis media, and sinusitis to more severe invasive disease including meningitis and bacteremia.

In the United States alone, pneumococcal pneumonia results in approximately 225,000 adult hospitalizations annually, representing substantial morbidity, healthcare costs, and mortality. In children under five years of age, Streptococcus pneumoniae remains the leading cause of vaccine-preventable deaths globally. The bacterium also accounts for over 50% of all bacterial meningitis cases in the United States, with associated high case-fatality rates.

A particular concern is the emergence of antibiotic-resistant pneumococcal strains. The World Health Organization has identified drug-resistant Streptococcus pneumoniae as one of the top antibiotic-resistant pathogens urgently requiring new therapeutic approaches. The U.S. Centers for Disease Control and Prevention designates drug-resistant Streptococcus pneumoniae as a “serious threat,” reflecting the significance of this resistance problem.

Current pneumococcal vaccines, including PCV20 and Pneumovax®23, provide important but incomplete protection against circulating disease. VAX-31’s broader serotype coverage aims to address this gap by potentially covering approximately 95% of invasive pneumococcal disease and approximately 88% of pneumococcal pneumonia in U.S. adults aged 50 and older, potentially providing an incremental 14-34% additional coverage for invasive disease beyond current standard vaccines.

Early Clinical Evidence Supports Next-Generation Approach

In May 2025, the FDA expanded its Breakthrough Therapy designation for VAX-31 to include prevention of pneumococcal pneumonia in addition to prevention of invasive pneumococcal disease in adults. This regulatory recognition was based on positive preliminary results from a Phase 1/2 study demonstrating that VAX-31 may represent a substantial improvement over existing therapeutic options.

The Phase 1/2 data showed that VAX-31 was well tolerated with a safety profile comparable to the established comparator vaccine PCV20. Importantly, VAX-31 demonstrated robust immune responses, measured by opsonophagocytic activity, across all 31 serotypes. The high-dose formulation of VAX-31 met predetermined superiority criteria for all 11 incremental serotypes not contained in PCV20. Additionally, for 18 of the 20 serotypes present in both vaccines, VAX-31 generated greater average immune responses, with seven of these achieving statistically significantly higher responses.

These early Phase 1/2 findings provided the scientific foundation supporting the FDA’s Breakthrough Therapy designation and justified advancement to the Phase 3 clinical programs currently underway.

Integration of Cutting-Edge Manufacturing Technology

Vaxcyte’s development of VAX-31 leverages the company’s carrier-sparing, site-specific conjugation technology platform. The company also utilizes XpressCF®, a cell-free protein synthesis platform exclusively licensed from Sutro Biopharma, Inc. Unlike conventional cell-based manufacturing approaches, the cell-free synthesis system allows production of complex proteins and antigens with potentially enhanced immunological characteristics and greater manufacturing consistency.

This technological approach represents an evolution in vaccine manufacturing methodology, allowing Vaxcyte to engineer vaccines with high fidelity to desired specifications while maintaining scalability for commercial production. The planned North Carolina manufacturing facility will employ these advanced production technologies to ensure consistent quality and availability of VAX-31 once the vaccine receives regulatory approval.

Future Development Path and Broader Pipeline

Beyond VAX-31, Vaxcyte is advancing a broader portfolio of pneumococcal vaccine candidates to address diverse clinical needs. VAX-24, a 24-valent pneumococcal conjugate vaccine, is designed to provide enhanced serotype coverage compared to currently available infant vaccines. VAX-XL, still in earlier developmental stages, further extends the serotype coverage approach through application of Vaxcyte’s advanced conjugation technology.

The company is also pursuing vaccine candidates addressing other significant bacterial pathogens. VAX-A1 represents a prophylactic vaccine candidate designed to prevent Group A Streptococcal infections, while VAX-GI targets prevention of Shigella infections, both addressing important global health needs.

This multi-program pipeline strategy demonstrates Vaxcyte’s commitment to applying its engineering platform to address multiple vaccine-preventable bacterial diseases, with VAX-31 representing the lead program advancing through late-stage clinical evaluation. The coming months and years will determine whether this next-generation pneumococcal vaccine approach achieves the clinical and regulatory milestones necessary to bring these vaccines to patients and clinicians seeking better protection against serious bacterial infections.