IDCRC study in Nature Communications demonstrates systemic and mucosal antibody responses to Neisseria gonorrhoeae following 4CMenB vaccination

Emory researchers and collaborators have reported new findings showing that immunization with the four-component meningococcal serogroup B vaccine (4CMenB, Bexsero^®) generates both systemic and mucosal antibody responses against Neisseria gonorrhoeae, the bacterium that causes gonorrhea. The results were published on September 23, 2026, in Nature Communications in the article, “Systemic and Mucosal Antibody Responses Against Neisseria gonorrhoeae (Ng) Outer Membrane Vesicle Antigens following Four-Component Meningococcal Serogroup B (4CMenB) Immunization in Healthy Adults: A Randomized Phase II Trial.”

The study, supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), was led by Varun K. Phadke, Soma Sannigrahi, Erin M. Scherer, Stacey A. Smith, Colleen F. Kelley, Maranda Leary, Sergio Cruz, Lori M. Newman, Christine Orndahl, E. Ross Colgate, Nadine Rouphael, Yih-Ling Tzeng, and David S. Stephens.

This was a double-blind, randomized, placebo-controlled phase 2 clinical trial designed to evaluate immune responses generated by a two-dose series of the meningococcal vaccine. The investigators found that vaccination induced both systemic and mucosal immunoglobulin G (IgG) responses to Neisseria gonorrhoeae outer membrane vesicle antigens. The findings add to a growing body of evidence indicating that 4CMenB induces cross-reactive immune responses against gonorrhea. The trial registration number is NCT04722003.

“Gonorrhea remains a major public health challenge worldwide with over 80 M cases each year, with increasing concerns regarding antimicrobial resistance and the absence of a licensed vaccine specifically designed to prevent infection,” said Dr. Phadke. “These findings provide important immunologic evidence supporting continued investigation of 4CMenB as a potential tool in gonorrhea prevention.”

The clinical trial evaluated healthy participants and focused on antibody responses at both systemic and rectal, vaginal and oropharyngeal, mucosal sites, which are particularly relevant for sexually transmitted infections. The study demonstrated that a two-dose 4CMenB vaccination regimen elicited systemic and the highest mucosal responses in vaginal secretions, which peak at Day 43 after vaccination.

The authors note that the results advance understanding of the immune mechanisms that may underlie previously observed associations between meningococcal B vaccination and reduced gonorrhea risk. The study provides important biological evidence that can inform future research efforts aimed at developing effective gonorrhea vaccines and prevention strategies.

Publication Details (citation)
Phadke, V. K., Sannigrahi, S., Scherer, E. M., Smith, S. A., Kelley, C. F., Leary, M., Cruz, S., Newman, L. M., Orndahl, C., Colgate, E. R., Rouphael, N., Tzeng, Y.-L., & Stephens, D. S. (2026). Systemic and Mucosal Antibody Responses Against Neisseria gonorrhoeae (Ng) Outer Membrane Vesicle Antigens following Four-Component Meningococcal Serogroup B (4CMenB) Immunization in Healthy Adults: A Randomized Phase II Trial. Nature Communications. https://doi.org/10.1038/s41467-026-77936-9

About Infectious Disease Clinical Research Consortium (IDCRC)
This activity is supported by the Infectious Diseases Clinical Research Consortium (IDCRC) through the NIAID (UM1AI148684 and UM1AI148576). The IDCRC, consisting of the Vaccine Treatment and Evaluation Units (VTEUs) and the IDCRC Leadership Group, was formed in 2019 to support the planning and implementation of infectious diseases clinical research that efficiently addresses the scientific priorities of NIAID. The consortium includes infectious diseases leaders and clinical researchers from Emory University, University of Maryland School of Medicine, Baylor College of Medicine, Cincinnati Children’s Medical Center and University of Cincinnati, FHI360, Fred Hutchinson Cancer Research Center, Johns Hopkins University, Kaiser Permanente Washington Health Research Institute, New York University, Saint Louis University, Vanderbilt University Medical Center, University of Alabama at Birmingham, University of Rochester, University of Washington, and NIAID. For more information about the IDCRC, please visit www.IDCRC.org.