scholarly journals Safety and Immunogenicity of a Novel Staphylococcus aureus Vaccine: Results from the First Study of the Vaccine Dose Range in Humans

2010 ◽  
Vol 17 (12) ◽  
pp. 1868-1874 ◽  
Author(s):  
Clayton Harro ◽  
Robert Betts ◽  
Walter Orenstein ◽  
Eun-Jeong Kwak ◽  
Howard E. Greenberg ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Response ◽  
Adverse Events ◽  
Immune Responses ◽  
Geometric Mean ◽  
Dose Range ◽  
Vaccine Dose ◽  
Double Blind Study ◽  
Mean Concentration ◽  
Positive Immune Response

ABSTRACT Merck V710 is a novel vaccine containing the conserved Staphylococcus aureus iron surface determinant B shown to be protective in animal models. A phase I, multicenter, double-blind study of the dose range was conducted to assess the immunogenicity and safety of an adjuvanted liquid formulation of V710. A total of 124 adults (18 to 55 years of age) were randomized 1:1:1:1 to receive one 0.5-ml intramuscular injection of V710 (5 μg, 30 μg, or 90 μg) or saline placebo. A positive immune response was defined as at least a 2-fold increase in IsdB-specific IgG levels from baseline levels. Local and systemic adverse events were assessed for 5 and 14 days, respectively, following vaccination. Positive immune responses were detected in 12 (67%) of the 18 subjects in the groups receiving 30 and 90 μg V710 tested at day 10. At day 14, a significantly greater proportion of subjects manifested a positive immune response with higher geometric mean concentrations in the V710 30-μg (86%; geometric mean concentration of 116 μg/ml) and 90-μg (87%; geometric mean concentration of 131 μg/ml) dose groups than in the V710 5-μg (29%; geometric mean concentration of 51 μg/ml) or placebo (4%; geometric mean concentration of 23 μg/ml) groups. Immune responses were durable through day 84. Subjects <40 and ≥40 years of age had comparable immune responses. The most common adverse events were injection-site pain, nausea, fatigue, and headache, usually of mild intensity. No immediate reactions or serious adverse events were reported. In this first study of V710 in humans, a single 30-μg or 90-μg dose was more immunogenic than the 5-μg dose or placebo. Immune responses were evident by 10 to 14 days after vaccination in most responders.

scholarly journals Vaccination strategy and anti - SARS-CoV-2 S titers in healthcare workers of the INT – IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy)

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ernesta Cavalcanti ◽  
Maria Antonietta Isgrò ◽  
Domenica Rea ◽  
Lucia Di Capua ◽  
Giusy Trillò ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Healthcare Workers ◽  
Geometric Mean ◽  
Vaccination Strategy ◽  
Antibody Responses ◽  
Cancer Center ◽  
Serum Samples ◽  
Humoral Immune ◽  
History Of

Abstract Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of people globally, requiring the development of billions of different vaccine doses. The SARS-CoV-2 spike mRNA vaccine (named BNT162b2/Pfizer), authorized by the FDA, has shown high efficacy in preventing SARS-CoV-2 infection after administration of two doses in individuals 16 years of age and older. In the present study, we retrospectively evaluated the differences in the SARS-CoV-2 humoral immune response after vaccine administration in the two different cohorts of workers at the INT - IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy): previously infected to SARS-CoV-2 subjects and not infected to SARS-CoV-2 subjects. Methods We determined specific anti-RBD (receptor-binding domain) titers against trimeric spike glycoprotein (S) of SARS-CoV-2 by Roche Elecsys Anti-SARS-CoV-2 S immunoassay in serum samples of 35 healthcare workers with a previous documented history of SARS-CoV-2 infection and 158 healthcare workers without, after 1 and 2 doses of vaccine, respectively. Moreover, geometric mean titers and relative fold changes (FC) were calculated. Results Both previously infected and not infected to SARS-CoV-2 subjects developed significant immune responses to SARS-CoV-2 after the administration of 1 and 2 doses of vaccine, respectively. Anti-S antibody responses to the first dose of vaccine were significantly higher in previously SARS-CoV-2-infected subjects in comparison to titers of not infected subjects after the first as well as the second dose of vaccine. Fold changes for subjects previously infected to SARS-CoV-2 was very modest, given the high basal antibody titer, as well as the upper limit of 2500.0 BAU/mL imposed by the Roche methods. Conversely, for naïve subjects, mean fold change following the first dose was low ($$ \overline{x} $$ x ¯ =1.6), reaching 3.8 FC in 72 subjects (45.6%) following the second dose. Conclusions The results showed that, as early as the first dose, SARS-CoV-2-infected individuals developed a remarkable and statistically significant immune response in comparison to those who did not contract the virus previously, suggesting the possibility of administering only one dose in previously SARS-CoV-2-infected subjects. FC for previously infected subjects should not be taken into account for the generally high pre-vaccination values. Conversely, FC for not infected subjects, after the second dose, were = 3.8 in > 45.0% of vaccinees, and ≤ 3.1 in 19.0%, the latter showing a potential susceptibility to further SARS-CoV-2 infection.

scholarly journals Clearance of Staphylococcus aureus Nasal Carriage Is T Cell Dependent and Mediated through Interleukin-17A Expression and Neutrophil Influx

2013 ◽  
Vol 81 (6) ◽  
pp. 2070-2075 ◽  
Author(s):  
Nathan K. Archer ◽  
Janette M. Harro ◽  
Mark E. Shirtliff
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Response ◽  
T Cell ◽  
Immune Responses ◽  
Neutrophil Migration ◽  
Nasal Carriage ◽  
Causal Connection ◽  
Content Type ◽  
Neutrophil Influx ◽  
Increased Risk

ABSTRACTThe anterior nares of humans are the major reservoir forStaphylococcus aureuscolonization. Approximately 20% of the healthy human population is persistently and 80% is intermittently colonized withS. aureusin the nasal cavity. Previous studies have shown a strong causal connection betweenS. aureusnasal carriage and increased risk of nosocomial infection, as well as increased carriage due to immune dysfunction. However, the immune responses that permit persistence or mediate clearance ofS. aureuson the nasal mucosa are fundamentally undefined. In this study, we developed a carriage model in C57BL/6J mice and showed that clearance begins 14 days postinoculation. In contrast, SCID mice that have a deficient adaptive immune response are unable to eliminateS. aureuseven after 28 days postinoculation. Furthermore, decolonization was found to be T cell mediated but B cell independent by evaluating carriage clearance in T-cell receptor β/δ (TCR-β/δ) knockout (KO) and IgH-μ KO mice, respectively. Upregulation of the cytokines interleukin 1β (IL-1β), KC (also termed CXC ligand 1 [CXCL1]), and IL-17A occurred following inoculation with intranasalS. aureus. IL-17A production was crucial for clearance, since IL-17A-deficient mice were unable to effectively eliminateS. aureuscarriage. Subsequently, cell differential counts were evaluated from nasal lavage fluid obtained from wild-type and IL-17A-deficient colonized mice. These counts displayed IL-17A-dependent neutrophil migration. Antibody-mediated depletion of neutrophils in colonized mice caused reduced clearance compared to that in isotype-treated controls. Our data suggest that the Th17-associated immune response is required for nasal decolonization. This response is T cell dependent and mediated via IL-17A production and neutrophil influx. Th17-associated immune responses may be targeted for strategies to mitigate distal infections originating from persistentS. aureuscarriage in humans.

scholarly journals 2712. Safety and Immunogenicity of two Doses of ExPEC4V Vaccine Against Extraintestinal Pathogenic Escherichia coli Disease in Healthy Adult Participants

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S954-S954
Author(s):  
William B Smith ◽  
Darren Abbanat ◽  
Bart Spiessens ◽  
Oscar Go ◽  
Wouter Haazen ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Immune Responses ◽  
Geometric Mean ◽  
Protein A ◽  
Fold Increase ◽  
Vaccine Safety ◽  
Double Blind Study ◽  
Double Blind ◽  
Grade 3 ◽  
O Antigens

Abstract Background The ExPEC4V vaccine contains 4 Escherichia coli O-antigens (O1A, O2, O6A, O25B) conjugated to exotoxin protein A and is being studied for prevention of Invasive Extraintestinal pathogenic E. coli (ExPEC) Disease (IED). This phase-2 double-blind study assessed safety and immunogenicity of ExPEC4V Clinical Trial Material (CTM), manufactured via a redesigned process (optimized O1A strain). Methods Participants (≥18 years) in stable health were randomized (3:1) to receive ExPEC4V dose 4:4:4:8 μg PS/serotype or placebo on Day 1 and second vaccination on Day 181 (6 months after first vaccination). Participants will be followed for safety until end of study at Day 360. Reactogenicity and immunogenicity (by ELISA, opsonophagocytic killing [OPA] assays) were evaluated pre-vaccination, and 15 days after first and second vaccinations (Day 195). Results Of 100 participants randomized (mean age 56, 48% males) and vaccinated (ExPEC4V, n = 75; placebo, n = 25), 97 completed Day 30. Solicited local AEs were higher for ExPEC4V (38.7%) than placebo (20%); most frequent was pain/tenderness (38.7% vs 20%). Solicited systemic AEs were higher in ExPEC4V (49.3%) than placebo (20%); most frequent was fatigue (32% vs. 12%). No serious or grade 3 solicited local AEs were reported. One participant in ExPEC4V experienced a grade 3 solicited systemic fatigue considered vaccine-related by investigator. ExPEC4V demonstrated immune responses against all serotypes at Day 15. Geometric mean titer effective concentration rank by serotypes was O2 > O1A > O6 > O25B (Figures 1 and 2). At Day 15, ≥ 82% of participants in ExPEC4V and none in placebo had ≥2-fold increase from baseline of ELISA titer for all serotypes. In ExPEC4V, ≥47% had ≥2-fold increase from baseline of OPA titer for all serotypes, while 8% in placebo had ≥2-fold increase only for O6A. Good correlation was observed between ELISA and OPA across serotypes (r ≥ 0.76). Conclusion ExPEC4V elicited robust and functional immune responses across all serotypes and was well tolerated with no vaccine safety findings. This study supports the development of future multivalent ExPEC vaccine to prevent IED. Disclosures All authors: No reported disclosures.

scholarly journals Immune Response to Meningococcal Serogroup C Conjugate Vaccine in Asplenic Individuals

2004 ◽  
Vol 72 (1) ◽  
pp. 332-337 ◽  
Author(s):  
Paul Balmer ◽  
Michelle Falconer ◽  
Paula McDonald ◽  
Nick Andrews ◽  
Emily Fuller ◽  
...  
Keyword(s):  
Immune Response ◽  
Matched Control ◽  
Risk Group ◽  
Geometric Mean ◽  
Control Group ◽  
Increased Risk ◽  
Specific Immunoglobulin ◽  
Bactericidal Antibody ◽  
Encapsulated Bacteria ◽  
Mean Concentration

ABSTRACT Asplenic individuals are known to be at increased risk of infection with encapsulated bacteria. Recent United Kingdom recommendations stated that this at-risk group should receive one dose of the meningococcal serogroup C conjugate (MCC) vaccine. However, the immune response of asplenic individuals to MCC vaccine is unknown. The immune response of asplenics (n = 130) to immunization with the MCC vaccine was investigated. Asplenic individuals had a significantly lower geometric mean titer (GMT) (157.8; 95% confidence interval [CI], 94.5 to 263.3) of bactericidal antibody in serum (SBA) than an age-matched control group (n = 48) (1448.2; 95% CI, 751.1 to 2792.0). However, 80% of asplenic individuals achieved the proposed protective SBA titer of ≥8. No differences were observed between the two groups in the serogroup C-specific immunoglobulin G geometric mean concentration. A significant reduction in SBA GMT or the number of responders achieving an SBA titer of ≥8 was observed if the reason for splenectomy was a medical cause or if MCC vaccination occurred <10 years after splenectomy. Individuals (n = 29) who did not achieve an SBA titer of ≥16 were offered a second dose of MCC vaccine. Analysis of the SBA response revealed that 61% (14 of 23) of the individuals who received a second dose achieved a protective titer. In total, 93% of asplenic individuals achieved a titer of ≥8 following MCC vaccination (one or two doses combined). We recommend that, following vaccination of asplenics, either the level of functional antibody should be determined, with a second dose of MCC vaccine offered to nonresponders, or two doses of MCC vaccine should be routinely offered.

Phase 1 Safety and Immunogenicity Study of a Respiratory Syncytial Virus Vaccine With an Adenovirus 26 Vector Encoding Prefusion F (Ad26.RSV.preF) in Adults Aged ≥60 Years

2020 ◽  
Vol 222 (6) ◽  
pp. 979-988 ◽  
Author(s):  
Kristi Williams ◽  
Arangassery Rosemary Bastian ◽  
Robert Allen Feldman ◽  
Edmund Omoruyi ◽  
Els de Paepe ◽  
...  
Keyword(s):  
Older Adults ◽  
Respiratory Syncytial Virus ◽  
Adverse Events ◽  
Immune Responses ◽  
Phase 1 ◽  
Geometric Mean ◽  
High Dose ◽  
Serious Adverse Events ◽  
Syncytial Virus ◽  
Vector Particles

Abstract Background Despite the high disease burden of respiratory syncytial virus (RSV) in older adults, there is no approved vaccine. We evaluated the experimental RSV vaccine, Ad26.RSV.preF, a replication-incompetent adenovirus 26 vector encoding the F protein stabilized in prefusion conformation. Methods This phase 1 clinical trial was performed in healthy adults aged ≥60 years. Seventy-two participants received 1 or 2 intramuscular injections of low-dose (LD; 5 × 1010 vector particles) or high-dose (HD; 1 × 1011 vector particles) Ad26.RSV.preF vaccine or placebo, with approximately 12 months between doses and 2-year follow-up for safety and immunogenicity outcomes. Results Solicited adverse events were reported by 44% of vaccine recipients and were transient and mild or moderate in intensity. No serious adverse events were related to vaccination. After the first vaccination, geometric mean titers for RSV-A2 neutralization increased from baseline (432 for LD and 512 for HD vaccine) to day 29 (1031 for LD and 1617 for HD). Pre-F–specific antibody geometric mean titers and median frequencies of F-specific interferon γ–secreting T cells also increased substantially from baseline. These immune responses were still maintained above baseline levels 2 years after immunization and could be boosted with a second immunization at 1 year. Conclusions Ad26.RSV.preF (LD and HD) had an acceptable safety profile and elicited sustained humoral and cellular immune responses after a single immunization in older adults.

scholarly journals Vaccination strategy and anti - SARS-CoV-2 S titers in healthcare workers of the INT – IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy)

2021 ◽  
Author(s):  
Ernesta Cavalcanti ◽  
Maria Antonietta Isgrò ◽  
Domenica Rea ◽  
Lucia Di Capua ◽  
Giusy Trillò ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Healthcare Workers ◽  
Geometric Mean ◽  
Vaccination Strategy ◽  
Antibody Responses ◽  
Cancer Center ◽  
Serum Samples ◽  
Humoral Immune ◽  
History Of

Abstract Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of people globally, requiring the development of billions of different vaccine doses. The SARS-CoV-2 spike mRNA vaccine (named BNT162b2/Pfizer), authorized by the FDA, has shown high efficacy in preventing SARS-CoV-2 infection after administration of two doses in individuals 16 years of age and older. In the present study, we retrospectively evaluated the differences in the SARS-CoV-2 humoral immune response after vaccine administration in the two different cohorts of workers at the INT - IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy): previously exposed to SARS-CoV-2 subjects and not exposed to SARS-CoV-2 subjects.Methods: We determined specific anti-RBD (receptor-binding domain) titers against trimeric spike glycoprotein (S) of SARS-CoV-2 by Roche Elecsys Anti-SARS-CoV-2 S immunoassay in serum samples of 35 healthcare workers with a previous documented history of SARS-CoV-2 infection and 158 healthcare workers without, after 1 and 2 doses of vaccine, respectively. Moreover, geometric mean titers and relative fold changes (FC) were calculated.Results: Both previously exposed and not exposed to SARS-CoV-2 subjects developed significant immune responses to SARS-CoV-2 after the administration of 1 and 2 doses of vaccine, respectively. Anti-S antibody responses to the first dose of vaccine were significantly higher in previously SARS-CoV-2-exposed subjects in comparison to titers of not exposed subjects after the first as well as the second dose of vaccine. Fold changes for subjects previously exposed to SARS-CoV-2 was very modest, given the high basal antibody titer, as well as the upper limit of 2500.0 BAU/mL imposed by the Roche methods. Conversely, for naïve subjects, mean fold change following the first dose was low ( =1.6), reaching 3.8 FC in 72 subjects (45.6%) following the second dose.Conclusions: The results showed that, as early as the first dose, SARS-CoV-2-exposed individuals developed a remarkable and statistically significant immune response in comparison to those who did not contract the virus previously, suggesting the possibility of administering only one dose in previously SARS-CoV-2-exposed subjects. FC for previously exposed subjects should not be taken into account for the generally high pre-vaccination values. Conversely, FC for not exposed subjects, after the second dose, were = 3.8 in >45.0% of vaccinees, and ≤3.1 in 19.0%, the latter showing a potential susceptibility to further SARS-CoV-2 infection.

scholarly journals Nasal and Salivary Mucosal Humoral Immune Response Elicited by mRNA BNT162b2 COVID-19 Vaccine Compared to SARS-CoV-2 Natural Infection

Vaccines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1499
Author(s):  
Mariapia Guerrieri ◽  
Beatrice Francavilla ◽  
Denise Fiorelli ◽  
Marzia Nuccetelli ◽  
Francesco Maria Passali ◽  
...  
Keyword(s):  
New York ◽  
Immune Response ◽  
Immune Responses ◽  
Humoral Immune Response ◽  
Natural Infection ◽  
Serum Antibody ◽  
Vaccine Dose ◽  
Humoral Immune ◽  
Antibody Assays ◽  
Nasal Secretions

SARS-CoV-2 antibody assays are crucial in managing the COVID-19 pandemic. Approved mRNA COVID-19 vaccines are well known to induce a serum antibody responses against the spike protein and its RBD. Mucosal immunity plays a major role in the fight against COVID-19 directly at the site of virus entry; however, vaccine abilities to elicit mucosal immune responses have not been reported. We detected anti-SARS-CoV-2 IgA-S1 and IgG-RBD in three study populations (healthy controls, vaccinated subjects, and subjects recovered from COVID-19 infection) on serum, saliva, and nasal secretions using two commercial immunoassays (ELISA for IgA-S1 and chemiluminescent assay for IgG-RBD). Our results show that the mRNA BNT162b2 vaccine Comirnaty (Pfizer/BioNTech, New York, NY, USA) determines the production of nasal and salivary IgA-S1 and IgG-RBD against SARS-CoV-2. This mucosal humoral immune response is stronger after the injection of the second vaccine dose compared to subjects recovered from COVID-19. Since there is a lack of validated assays on saliva and nasal secretions, this study shows that our pre-analytical and analytical procedures are consistent with the data. Our findings indicate that the mRNA COVID-19 vaccine elicits antigen-specific nasal and salivary immune responses, and that mucosal antibody assays could be used as candidates for non-invasive monitoring of vaccine-induced protection against viral infection.

scholarly journals Immunogenicity and Reactogenicity of SARS-CoV-2 Vaccines in Patients With Cancer: The CANVAX Cohort Study

2021 ◽  
Author(s):  
Vivek Naranbhai ◽  
Claire A. Pernat ◽  
Alexander Gavralidis ◽  
Kerri J. St Denis ◽  
Evan C. Lam ◽  
...  
Keyword(s):  
Cohort Study ◽  
Immune Responses ◽  
Geometric Mean ◽  
Vaccine Dose ◽  
Solid Organ ◽  
Healthy Controls ◽  
Neutralization Titer ◽  
Patients With Cancer ◽  
Vaccine Type ◽  
Antibody Titers

PURPOSE The immunogenicity and reactogenicity of SARS-CoV-2 vaccines in patients with cancer are poorly understood. METHODS We performed a prospective cohort study of adults with solid-organ or hematologic cancers to evaluate anti–SARS-CoV-2 immunoglobulin A/M/G spike antibodies, neutralization, and reactogenicity ≥ 7 days following two doses of mRNA-1273, BNT162b2, or one dose of Ad26.COV2.S. We analyzed responses by multivariate regression and included data from 1,638 healthy controls, previously reported, for comparison. RESULTS Between April and July 2021, we enrolled 1,001 patients; 762 were eligible for analysis (656 had neutralization measured). mRNA-1273 was the most immunogenic (log10 geometric mean concentration [GMC] 2.9, log10 geometric mean neutralization titer [GMT] 2.3), followed by BNT162b2 (GMC 2.4; GMT 1.9) and Ad26.COV2.S (GMC 1.5; GMT 1.4; P < .001). The proportion of low neutralization (< 20% of convalescent titers) among Ad26.COV2.S recipients was 69.9%. Prior COVID-19 infection (in 7.1% of the cohort) was associated with higher responses ( P < .001). Antibody titers and neutralization were quantitatively lower in patients with cancer than in comparable healthy controls, regardless of vaccine type ( P < .001). Receipt of chemotherapy in the prior year or current steroids were associated with lower antibody levels and immune checkpoint blockade with higher neutralization. Systemic reactogenicity varied by vaccine and correlated with immune responses ( P = .002 for concentration, P = .016 for neutralization). In 32 patients who received an additional vaccine dose, side effects were similar to prior doses, and 30 of 32 demonstrated increased antibody titers (GMC 1.05 before additional dose, 3.17 after dose). CONCLUSION Immune responses to SARS-CoV-2 vaccines are modestly impaired in patients with cancer. These data suggest utility of antibody testing to identify patients for whom additional vaccine doses may be effective and appropriate, although larger prospective studies are needed.

scholarly journals Persistence of Immune Responses Through 36 Months in Healthy Adults After Vaccination With a Novel Staphylococcus aureus 4-Antigen Vaccine (SA4Ag)

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
C Buddy Creech ◽  
Robert W Frenck ◽  
Anne Fiquet ◽  
Robert Feldman ◽  
Martin K Kankam ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Responses ◽  
Capsular Polysaccharide ◽  
Geometric Mean ◽  
Healthy Adults ◽  
Blood Draw ◽  
Transporter Protein ◽  
Fibrinogen Binding ◽  
Antigen Vaccine ◽  
Binding Inhibition

Abstract Background Staphylococcus aureus causes serious health care– and community-associated disease, requiring improved preventive measures such as vaccines. The investigational S. aureus 4-antigen vaccine (SA4Ag), comprising capsular polysaccharide serotypes 5 and 8 (CP5 and CP8) conjugated to CRM197, recombinant mutant clumping factor A (rmClfA), and recombinant manganese transporter protein C (rP305A or rMntC), was well tolerated, inducing robust functional immune responses to all 4 antigens through 12 months postvaccination. This is a serological extension study through 36 months postvaccination. Methods In 2 previous studies, healthy adults received SA4Ag, SA3Ag (without rMntC), or placebo; serology was also assessed at ~24 and ~36 months postvaccination. Functional immune responses (antibody responses that facilitate killing of S. aureus or neutralize S. aureus virulence mechanisms) were assessed with opsonophagocytic activity killing assays (CP5 or CP8) and a fibrinogen-binding inhibition assay (ClfA). A competitive Luminex immunoassay assessed ClfA and rMntC responses. Adverse events within 48 hours of blood draw were recorded. Results Four hundred forty subjects (18–64 years old, 255; 65–85 years old, 185) were enrolled. At 24 and 36 months postvaccination, subjects receiving SA4Ag had substantially higher geometric mean titers (GMTs) for CP5, CP8, and ClfA vs baseline; geometric mean fold rises (GMFRs) from baseline to month 36 were 2.7–8.1. For rMntC, 36-month GMTs declined from peak levels but remained above baseline for all SA4Ag groups; GMFRs from baseline to month 36 were 1.8 and 1.5 in the younger and older cohorts, respectively. Conclusions Persistent functional immune responses to S. aureus antigens were observed through 36 months in healthy adults. ClinicalTrials.gov NCT01643941 and NCT01364571.

scholarly journals Carrier-Induced Hyporesponsiveness to Pneumococcal Conjugate Vaccines: Unraveling the Influence of Serotypes, Timing, and Previous Vaccine Dose

2020 ◽  
Author(s):  
Ron Dagan ◽  
Qin Jiang ◽  
Christine Juergens ◽  
James Trammel ◽  
William C Gruber ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Immune Response ◽  
Immune Responses ◽  
Vaccine Dose ◽  
Double Blind ◽  
Conjugate Vaccines ◽  
Pneumococcal Conjugate Vaccines ◽  
Time Points ◽  
Specific Immunoglobulin ◽  
Lower Immune Response

Abstract Background Pneumococcal conjugate vaccines (PCVs) elicit lower immune response against serotypes carried before or at the time of vaccination (hyporesponsiveness) in infants. The limited studies conducted to date did not permit comprehensive insights regarding this phenomenon. This study, the largest ever conducted with both carriage and serologic endpoints, attempted to add insight on serotype-specific hyporesponsiveness in relation to the number of PCV doses administered before carriage acquisition. Methods In a double-blind randomized clinical trial (n = 1754 infants), 7-valent or 13-valent PCV was administered at ages 2, 4, 6, and 12 months. New acquisition was defined based on nasopharyngeal swabs at ages 2, 4, 6, 7, and 12 months. Serotype-specific immunoglobulin G levels were obtained 1 month after the infant series and 1 month after the toddler dose. Results A lower immune response after the infant series and the toddler dose was consistently observed for carriers of serotypes 6A, 6B, 18C, and 19F at predefined time points, with a similar trend observed in carriers of serotype 23F. In contrast, carriage of serotypes 9V, 14, and 19A did not generally affect immune responses. For some but not all serotypes, hyporesponsiveness was decreased with an increased number of vaccine doses received before acquisition. A complex interrelationship between carriage and immune response was observed between cross-reacting serotypes. Conclusions Carrier-induced hyporesponsiveness to PCVs is common, differs among serotypes, and depends on timing of carriage acquisition and prior number of administered PCV doses. Clinical Trials Registration NCT00508742.

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