A novel vaccine candidate for challenging bacteria

For years, researchers at the National Institutes of Health, the Centers for Disease Control and Prevention (CDC) and pharmaceutical companies have tried and failed to develop a successful gonorrhea vaccine. Clinical trials have disappointed; potential vaccine candidates have not generated an immune response.

Gonorrhea typically is treated with antibiotics, but Neisseria gonorrhoeae bacteria have become increasingly resistant to them, and drug options have dwindled. In 2006, the CDC had five recommended antibiotics for gonorrhea; now only one option remains for effective treatment in the United States, with approximately 700,000 reported cases of gonorrhea in 2021.

Now, “superbug” gonorrhea strains have emerged in the United States that are drug-resistant, making the need for a vaccine ever so more important. The CDC has called for increased research funding for a gonorrhea vaccine and has expanded its surveillance program recently.

While several researchers are working on developing a vaccine, Mercer University’s pharmaceutical scientist Dr. Martin D’Souza and his research team of graduate student Priyal Bagwe and longtime collaborator Dr. Susu Zughaier of Qatar University, have developed an innovative gonorrhea vaccine candidate that takes a novel approach.

Many of the previous vaccine attempts involve fragmented N. gonorrhoeae strains in suspension, but Dr. D’Souza’s potential vaccine involves the use of the whole-cell, inactivated bacteria in a dry powder state. The inactivated bacteria are spray-dried and incorporated into microparticles, which are then loaded into polymeric microneedles. A microneedle patch is applied to the skin like an adhesive patch, with the microneedles dissolving in less than 10 minutes after application. The vaccine microparticles are released into the skin, where they are picked up by immune cells.

Since the final microneedle vaccine is in dry form, this vaccine does not require refrigeration that current vaccines do. This vaccine can be kept at room temperature for an extended period.

“Most vaccines are given by intramuscular or subcutaneous injection, which can be painful, but microneedles are pain-free, as they do not reach the pain receptors of the skin,” said Dr. D’Souza, professor of pharmaceutical sciences and co-director of Mercer’s Center for Drug Delivery Research.

He also incorporated this vaccine candidate into an oral dissolving film, much like breath freshener strips currently on the market that dissolve in the mouth. These films are produced on a 3D printer in the lab.

Previous liquid vaccine candidates contained fragmented gonorrhea bacteria strains, but the immune responses were lackluster. Dr. D’Souza’s vaccine candidate uses “whole-cell, fixed” bacteria in microparticles, which he believes is the key to triggering the body’s immune cells into action.

His research team conducted a preliminary study of this potential vaccine on mice infected with gonorrhea. All the mice that received the vaccine dose survived and generated a very strong antibody response to the vaccine. The National Institute of Allergy and Infectious Diseases funded this research with a $464,658 grant. Dr. D’Souza plans on submitting another proposal this month to continue the research, this time to test if the vaccine can confer immunity when exposed to two new drug-resistant strains of the gonorrhea bacteria.