Vaxcyte Announces Significant Development of First-of-Its-Kind PCV31

Vaxcyte recently announced significant progress in the clinical development of VAX-31, its 31-valent pneumococcal conjugate vaccine (PCV31) candidate, according to a news release.¹ As the highest-valent PCV currently under development, VAX-31 is being positioned as a potential best-in-class protection against pneumococcal disease for both adults and infants.

“The continued advancement of VAX-31 in adults reflects disciplined execution across our phase 3 clinical program, which was finalized in consultation and alignment with the FDA, as we work toward delivering a best-in-class, next-generation PCV with the potential to set a new standard of care for adults and children,” Grant Pickering, CEO and co-founder of Vaxcyte, said in the news release. “In adults, evaluating VAX-31 in settings that reflect real-world vaccination practice, including coadministration with a seasonal influenza vaccine and in individuals with prior pneumococcal vaccination, will provide important insights into how VAX-31 is expected to perform across the adult population.”

Dosing has commenced in the phase 3 OPUS-2 trial, which evaluates the vaccine's performance when administered concomitantly with seasonal influenza vaccines in pneumococcal-naïve adults 50 years and older. Simultaneously, Vaxcyte completed enrollment for a phase 2 infant dose-finding study, marking a critical step toward addressing the leading cause of vaccine-preventable deaths in children under 5 globally.¹

READ MORE: PPSV23 Ceases Pneumococcus Cases Among Serotype 4 Outbreak

For pharmacists, who serve as the most accessible members of the health care team, these advancements represent a vital expansion of the tools available to combat infectious disease burden, which saw invasive pneumococcal disease (IPD) incidence nearly double between 2012 and 2024.^2,3

The clinical relevance of VAX-31 is underscored by its design to cover approximately 95% of invasive pneumococcal disease (IPD)-causing serotypes circulating in US adults over 50 years.¹ This broad spectrum is necessary because, despite the efficacy of current options like PCV20 and the recently approved PCV21, the phenomenon of serotype replacement continues to push nonvaccine serotypes into prominence.³

To provide pharmacists and the FDA with real-world data, the OPUS-2 trial utilizes a randomized, double-blind approach to compare concomitant and sequential administration with flu shots, and the upcoming OPUS-3 study will specifically evaluate VAX-31 in adults who have previously received other pneumococcal vaccines, such as the 23-valent pneumococcal polysaccharide vaccine (PPSV23) or PCV20.¹

The push for higher valency, however, brings technical challenges regarding immunogenicity. Research comparing earlier vaccines like PCV7 and PCV13 with newer PCV15 and PCV20 formulations suggested that increasing the number of polysaccharides can sometimes result in lower antibody responses for common serotypes, according to the Canada Communicable Disease Report.⁴

To mitigate this, some pipeline candidates—such as Inventprise’s PCV25—are utilizing innovative hydrazide-polyethylene glycol-hydrazide (Hz-PEG-Hz) linker technology to reduce carrier-induced immune interference.² Vaxcyte’s own platform similarly aims to maintain robust immune responses while expanding coverage, a necessity as the CDC recently lowered the routine vaccination age to 50 years old.^1,5,6

In the pediatric sector, VAX-31 is designed to protect against approximately 92% of IPD serotypes and 96% of acute otitis media cases in children.¹ This is particularly important because PCVs provide nasal immunity by stimulating antibodies in the nasal mucosa, which prevents colonization and is a feature missing from PPSV23.⁶

Furthermore, dosing schedules remain a point of clinical discussion, and the World Health Organization supports a 2+1 schedule for healthy children. However, some data indicates that a 3+1 schedule provides superiority.⁴ Vaxcyte’s ongoing infant study follows the 4-dose series to ensure maximum protection.¹

As the landscape shifts toward sophisticated platforms like Vaxcyte’s cell-free protein synthesis system, the goal remains a serotype-independent vaccine—the holy grail of the pneumococcal vaccine industry.^1,7

Pharmacists can bridge current gaps by using the PneumoRecs VaxAdvisor app to navigate complex guidelines and stay updated on Vaxcyte’s expanding pipeline, which also includes candidates for Group A Streptococcus and Shigella.^1,2,5 With Vaxcyte committing up to $1 billion toward US manufacturing, the infrastructure is being set to support these next-generation preventions.¹

“We expect to announce topline data from the ongoing OPUS-1 Phase 3 pivotal, noninferiority trial in the fourth quarter of 2026 and results from these additional Phase 3 adult studies in the first half of 2027, keeping us on track toward a planned Biologics License Application submission,” concluded Pickering, according to the release.

READ MORE: Pneumococcal Resource Center

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REFERENCES

1. Vaxcyte advances adult and infant programs for VAX-31, a potential best-in-class, next-generation pneumococcal conjugate vaccine. News Release. Vaxcyte, Inc. January 22, 2026. Accessed March 18, 2026. https://www.biospace.com/press-releases/vaxcyte-advances-adult-and-infant-programs-for-vax-31-a-potential-best-in-class-next-generation-pneumococcal-conjugate-vaccine

2. Nowosielski B. New 25-valent pneumococcal vaccine shows promise in global disease coverage. Drug Topics. March 13, 2026. Accessed March 18, 2026. https://www.drugtopics.com/view/new-25-valent-pneumococcal-vaccine-shows-promise-in-global-disease-coverage

3. Nowosielski B. Rise in IPD calls for development of more pneumococcal vaccines. Drug Topics. November 17, 2025. Accessed March 18, 2026. https://www.drugtopics.com/view/rise-in-ipd-calls-for-development-of-more-pneumococcal-vaccines

4. De Wals P. PCV13, PCV15 or PCV20: Which vaccine is best for children in terms of immunogenicity? Can Commun Dis Rep. 2024 Jan 1;50(1-2):35-39. doi: 10.14745/ccdr.v50i12a04.

5. Pneumococcal vaccine recommendations. CDC. February 25, 2026. Accessed March 18, 2026. https://www.cdc.gov/pneumococcal/hcp/vaccine-recommendations/index.html

6. Katella K. Should i get the pneumococcal vaccine? 5 things to know. Yale Medicine. December 12, 2024. Accessed March 18, 2026. https://www.yalemedicine.org/news/should-i-get-the-pneumococcal-vaccine-5-things-to-know

7. Musher DM, Anderson R, Feldman C. The remarkable history of pneumococcal vaccination: an ongoing challenge. Pneumonia (Nathan). 2022 Sep 25;14(1):5. doi: 10.1186/s41479-022-00097-y