Assessment of Serum Bactericidal and Opsonophagocytic Activity of Antibodies to Gonococcal Vaccine Targets

Semchenko, Evgeny A.; Jen, Freda E.-C.; Jennings, Michael P.; Seib, Kate L.

doi:10.1007/978-1-0716-1900-1_19

Cited by 6 publications

(6 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although immune correlates of protection against N. gonorrhoeae in humans have not been defined, complement-dependent antibody-mediated bacterial killing (serum bactericidal activity, SBA) may be considered a surrogate of protection against vaginal colonization in preclinical vaccine evaluation [ 36 , 48 ]. For at least two vaccine antigens, the 2C7 LOS mimotope and chimeric antigen comprising NGO0265 plus FtsN [ 33 , 80 ], evidence suggests that SBA may constitute a mechanistic correlate of protection against gonococcal vaginal colonization of mice.…”

Section: Discussionmentioning

confidence: 99%

“…Although the correlates of protection against natural gonococcal mucosal infection in humans remain unclear, most vaccine studies rely on complement-dependent antibody-mediated bacterial killing (also called serum bactericidal activity, or SBA), which serves as a correlate of protective immunity to N. meningitidis in humans [ 34 ]. SBA is regarded as an in vitro surrogate of protection to guide the evaluation of vaccine candidates’ efficacy in vitro [ 35 , 36 ]. Other mechanisms of protection may include antibody-dependent opsonophagocytosis, the blocking of bacteria adhesion/invasion at the site of colonization, and T cell responses [ 37 ], although these are not all confirmed in human studies or unequivocally in experimental mouse models of gonococcal vaginal colonization.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In Vitro Pre-Clinical Evaluation of a Gonococcal Trivalent Candidate Vaccine Identified by Transcriptomics

Roe,

Felter,

Zheng

et al. 2023

Vaccines

View full text Add to dashboard Cite

Gonorrhea, a sexually transmitted disease caused by Neisseria gonorrhoeae, poses a significant global public health threat. Infection in women can be asymptomatic and may result in severe reproductive complications. Escalating antibiotic resistance underscores the need for an effective vaccine. Approaches being explored include subunit vaccines and outer membrane vesicles (OMVs), but an ideal candidate remains elusive. Meningococcal OMV-based vaccines have been associated with reduced rates of gonorrhea in retrospective epidemiologic studies, and with accelerated gonococcal clearance in mouse vaginal colonization models. Cross-protection is attributed to shared antigens and possibly cross-reactive, bactericidal antibodies. Using a Candidate Antigen Selection Strategy (CASS) based on the gonococcal transcriptome during human mucosal infection, we identified new potential vaccine targets that, when used to immunize mice, induced the production of antibodies with bactericidal activity against N. gonorrhoeae strains. The current study determined antigen recognition by human sera from N. gonorrhoeae-infected subjects, evaluated their potential as a multi-antigen (combination) vaccine in mice and examined the impact of different adjuvants (Alum or Alum+MPLA) on functional antibody responses to N. gonorrhoeae. Our results indicated that a stronger Th1 immune response component induced by Alum+MPLA led to antibodies with improved bactericidal activity. In conclusion, a combination of CASS-derived antigens may be promising for developing effective gonococcal vaccines.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In Vitro Pre-Clinical Evaluation of a Gonococcal Trivalent Candidate Vaccine Identified by Transcriptomics

Roe,

Felter,

Zheng

et al. 2023

Vaccines

View full text Add to dashboard Cite

show abstract

“…OPA assays were performed as previously described [ 33 ]. Fresh venous blood was collected from healthy subjects, shaken, and mixed well; polymorphonuclear leukocytes (PMNs) were extracted according to the manufacturer's instructions with Polymorphprep™ (Axis-Shield, Norway) separation solution, and the cells were diluted to 1 × 10 5 cells/mL in RPMI 1640 medium.…”

Section: Methodsmentioning

confidence: 99%

“…SBA assays were performed as previously described [ 33 ]. N. gonorrhoeae FA1090 was inoculated onto GCB plates and incubated at 37 °C in an incubator containing 5 % CO 2 for 16–18 h. Colonies were picked to adjust the colony number to 4 × 10 6 CFU/40 μl.…”

Section: Methodsmentioning

confidence: 99%

Characterization of protective immune responses against Neisseria gonorrhoeae induced by intranasal immunization with adhesion and penetration protein

Xia,

Lu,

Wang

et al. 2024

Heliyon

View full text Add to dashboard Cite

“…While there is less consensus about the contribution of opsonophagocytic killing activity (OPKA) to meningococcal vaccine efficacy, OPKA may help protect individuals whose antibody titer is not sufficient to evoke SBA and in those with terminal complement deficiencies who cannot mount SBA (39,(41)(42)(43). Assays to examine SBA and OPKA in N. gonorrhoeae are being developed (44,45). The premise for both SBA and opsonophagocytosis is that vaccine-elicited antibody binds to the surface of bacteria, but this property of vaccination is not typically evaluated in the context of intact pathogens.…”

Section: Introductionmentioning

confidence: 99%

Evaluating vaccine-elicited antibody activities againstNeisseria gonorrhoeae:cross-protective responses elicited by the 4CMenB meningococcal vaccine

Gray¹,

Thomas²,

Lamb³

et al. 2023

Preprint

View full text Add to dashboard Cite

The bacterial pathogenNeisseria gonorrhoeaeis an urgent global health problem due to increasing numbers of infections, coupled with rampant antibiotic resistance. Vaccines against gonorrhea are being prioritized to combat drug-resistantN. gonorrhoeae. Meningococcal serogroup B vaccines such as 4CMenB are predicted by epidemiology studies to cross-protect individuals from natural infection withN. gonorrhoeaeand elicit antibodies that cross-react withN. gonorrhoeae. Evaluation of vaccine candidates for gonorrhea requires a suite of assays for predicting efficacy in vitro and in animal models of infection, including the role of antibodies elicited by immunization. Here we present assays to evaluate antibody functionality after immunization: antibody binding to intactN. gonorrhoeae, serum bactericidal activity, and opsonophagocytic killing activity using primary human neutrophils (polymorphonuclear leukocytes). These assays were developed with purified antibodies againstN. gonorrhoeaeand used to evaluate serum from mice that were vaccinated with 4CMenB or given alum as a negative control. Results from these assays will help prioritize gonorrhea vaccine candidates for advanced preclinical to early clinical study and will contribute to identifying correlates and mechanisms of immune protection againstN. gonorrhoeae.

show abstract

Assessment of Serum Bactericidal and Opsonophagocytic Activity of Antibodies to Gonococcal Vaccine Targets

Cited by 6 publications

References 16 publications

In Vitro Pre-Clinical Evaluation of a Gonococcal Trivalent Candidate Vaccine Identified by Transcriptomics

In Vitro Pre-Clinical Evaluation of a Gonococcal Trivalent Candidate Vaccine Identified by Transcriptomics

Characterization of protective immune responses against Neisseria gonorrhoeae induced by intranasal immunization with adhesion and penetration protein

Evaluating vaccine-elicited antibody activities againstNeisseria gonorrhoeae:cross-protective responses elicited by the 4CMenB meningococcal vaccine

Contact Info

Product

Resources

About