Geometric Mean Immunoglobulin G Research Articles

930 SAFETY, TOLERABILITY AND IMMUNOGENICITY OF 15-VALENT PNEUMOCOCCAL CONJUGATE VACCINE + PPV23 12 MONTHS LATER IN HEALTHY ADULTS ≥ 50

Abstract Background Older adults are at increased risk of pneumococcal disease (PD). V114, an investigational 15-valent Pneumococcal Conjugate Vaccine (PCV), contains all serotypes in 13-valent PCV (PCV13) plus serotypes 22F and 33F. This phase 3 trial evaluated the safety, tolerability and immunogenicity of V114 or PCV13 followed 12 months later by PPSV23 in healthy adults aged ≥50 years. Materials/Method 652 eligible adults were randomised 1:1 to receive V114 or PCV13 followed by PPSV23 12 months later. Solicited and non-solicited adverse events (AEs) were collected after each vaccination. Serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) antibodies were measured at Day 1, Day 30, Month 12 and Month 13. Results The most common solicited AEs following PCV were injection-site pain, fatigue and myalgia; higher proportions of participants with solicited AEs were observed in the V114 group; however, the differences were not clinically significant, as most AEs were mild and of short duration. The most common solicited AEs following PPSV23 were injection-site pain, injection-site swelling, fatigue and myalgia; these events were comparable across both intervention groups. The proportion of participants with serious AEs were low in both groups and none reported to be vaccine related. No deaths occurred during the study. Serotype-specific OPA geometric mean titres (GMTs) and IgG geometric mean concentrations (GMCs) were comparable between the groups for all 15 serotypes 30 days post-vaccination with PPSV23. OPA GMTs and IgG GMCs were comparable between PCV groups for the 13 shared serotypes and higher in V114 than PCV13 for serotypes 22F and 33F 30 days and 12 months post-vaccination with PCV. V114 elicited an immune response that persisted for at least 12 months. Conclusion Sequential administration of V114 and PPSV23 is well tolerated, immunogenic and generally comparable to PCV13 followed by PPSV23 in healthy adults ≥50 years of age.

Lot-to-lot consistency, safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, in healthy adults aged ≥50 years: A randomized phase 3 trial (PNEU-TRUE)

BackgroundOlder adults are at risk of pneumococcal disease and associated morbidity and mortality. This phase 3 study (V114-020) assessed lot-to-lot consistency across safety and immunogenicity outcomes for V114, a 15-valent pneumococcal conjugate vaccine (PCV), in healthy adults aged ≥ 50 years. MethodsAdults were randomized in a 3:3:3:1 ratio to receive a single dose of one of three lots of V114 or 13-valent PCV (PCV13), stratified by age (50–64 years, 65–74 years, and ≥ 75 years). Serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) antibodies were evaluated at baseline (Day 1) and 30 days post-vaccination. Non-serious and serious adverse events (AEs) were evaluated post-vaccination through 14 days and Month 6, respectively. ResultsOf 2340 participants enrolled, 2282 (97.5%) completed the study. Proportions of participants experiencing ≥ 1 AE were 81.0%, 77.4%, and 78.0% for V114 lots 1, 2, and 3, respectively. Comparison of V114 combined lots with PCV13 showed that proportions of participants experiencing AEs, solicited AEs, and serious AEs were comparable for both vaccines, with the exception of injection-site pain (more frequently reported with V114). OPA geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) at 30 days post-vaccination were comparable across V114 lots, and all lots met predefined equivalence criteria for all 15 vaccine serotypes (lower and upper limits of the 95% confidence intervals of serotype-specific OPA GMT ratios for all possible pairwise comparisons across the three lots were within the equivalence margin of 0.5–2.0). Serotype-specific OPA GMTs and IgG GMCs were comparable in the V114 combined lots and PCV13 groups for the 13 shared serotypes and higher in the V114 group for serotypes unique to V114 (22F and 33F). ConclusionsV114 is well tolerated with a consistent safety profile and immune response across manufacturing lots.Clinical trials registration: NCT03950856 (www.clinicaltrials.gov); 2018-004266-33 (EudraCT).

Waning of Anti-spike Antibodies in AZD1222 (ChAdOx1) Vaccinated Healthcare Providers: A Prospective Longitudinal Study.

IntroductionCoronavirus disease 2019 (COVID-19) vaccines are nothing short of a miracle story halting the pandemic across the globe. Nearly half of the global population has received at least one dose. Nevertheless, antibody levels in vaccinated people have shown waning, and breakthrough infections have occurred. Our study aims to measure antibody kinetics following AZD1222 (ChAdOx1) vaccination six months after the second dose and the factors affecting the kinetics.Materials and methodsWe conducted a prospective longitudinal study monitoring for six months after the second of two AZD1222 (ChAdOx1) vaccine doses in healthcare professionals and healthcare facility employees at Veer Surendra Sai Institute of Medical Sciences and Research (included doctors, nurses, paramedical staff, security and sanitary workers, and students). Two 0.5-mL doses of the vaccine were administered intramuscularly, containing 5 x 1010 viral particles 28 to 30 days between doses. We collected blood samples one month after the first dose (Round 1), one month after the second dose (Round 2), and six months after the second dose (Round 3). We tested for immunoglobulin G (IgG) levels against the receptor-binding domain of the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by chemiluminescence microparticle immunoassay. We conducted a linear mixed model analysis to study the antibody kinetics and influencing factors.ResultsOur study included 122 participants (mean age, 41.5 years; 66 men, 56 women). The geometric mean IgG titers were 138.01 binding antibody units (BAU)/mL in Round 1, 176.48 BAU/mL in Round 2, and 112.95 BAU/mL in Round 3. Seven participants showed seroreversion, and 11 had breakthrough infections. Eighty-six participants showed a substantial decline in antibody titer from Rounds 2 to 3. Persons aged 45 or older had higher mean titer than people aged younger than 45 years. Overweight and obese (BMI ≥ 25 kg/m2) had a higher mean titer than average or underweight persons. The only significant predictor of IgG titers at six months was SARS-CoV-2 infection on mixed model analysis.ConclusionWe found a substantial decline in antibody levels leading to seven cases of seroreversion in healthcare professionals who received the ChAdOx1 vaccine. History of prior COVID-19 was the only significant factor in antibody levels at six months. Seroreversion and breakthrough infection warrant further research into the optimal timing and potential benefits of booster doses of the AZD1222 (ChAdOx1) COVID-19 vaccine.

Safety and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, in adults living with HIV.

Objectives:To evaluate safety and immunogenicity of V114 [15-valent pneumococcal conjugate vaccine (PCV) containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F], followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) 8 weeks later, in adults living with HIV.Design:In this phase 3 study (V114-018; NCT03480802), pneumococcal vaccine-naive adults with HIV (CD4+ cell count ≥50 cells/μl, plasma HIV RNA <50 000 copies/ml, receiving antiretroviral therapy) were randomized 1 : 1 to receive one dose of V114 or licensed 13-valent PCV (PCV13) on day 1; participants received PPSV23 at week 8.Methods:Adverse events and serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) antibodies were evaluated after each vaccination.Results:Of 302 participants enrolled, 292 (96.7%) completed the study. Proportions of participants experiencing at least one adverse event were 73.0 and 62.7% in the V114 and PCV13 groups following PCV and 60.7 and 71.6% following PPSV23. Most solicited adverse events were of mild or moderate severity and short duration. OPA geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) were generally comparable between groups for shared serotypes at day 30 and maintained at week 12. OPA and IgG responses for additional serotypes in V114 (22F, 33F) were higher following V114 than PCV13 at day 30 but comparable at week 12, 30 days post-PPSV23.Conclusion:In pneumococcal vaccine-naive adults living with HIV, V114 was well tolerated and induced immune responses for all 15 pneumococcal serotypes. V114 can be followed by PPSV23 8 weeks later to broaden serotype coverage.

MRNA SARS-CoV-2 Immunization Confers Robust Antibody Response in Occupational Healthcare Workers and Fosters Workplace Safety.

mRNA SARS-CoV-2 Immunization Confers Robust Antibody Response in Occupational Healthcare Workers and Fosters Workplace Safety.

Is there an association between socioeconomic status and immune response to infant and childhood vaccination in the Netherlands?

IntroductionSocioeconomic status (SES) is a well-known determinant of health, but its relation with vaccine-induced immunity is less documented. We explored the association between SES and immunoglobulin G (IgG) levels against vaccine-preventable diseases in vaccinated children in the Dutch National Immunization Programme. MethodsData from a population-wide cross-sectional serosurvey in the Netherlands (2006–2007) were used. We compared geometric mean IgG concentrations/titers (GMC/T ratios) against measles, mumps, rubella, Haemophilus influenzae type b (Hib), Neisseria meningococcus type C, diphtheria, tetanus, poliovirus types 1,2,3 and pertussis in children of high versus low SES by linear regression analysis. We included 894 children (0–12 years) at one of two timeframes: 1 month to 1 year, or 1–3 years after vaccination. Mother’s educational level and net household income served as binary indicators of SES. ResultsOf 58 possible associations of vaccine-induced antibody responses with educational level and 58 with income, 10 (9%) were statistically significant: 2 favouring (that is, with higher IgG levels at) high educational level (for Hib 1 m-1y after vaccination (GMC/T ratio: 2.99, 95%CI: 1.42–6.30) and polio 2 1 m-1y after the 9-year booster dose (1.14, 1.01–1.27)) and 8 favouring low income (polio 1, 2 and 3 1 m-1y after the 11-month booster (0.74, 0.58–0.94; 0.79, 0.64–0.97; 0.72, 0.55–0.95), polio 3 and pertussis 1-3y after the 11-month booster (0.70, 0.56–0.88; pertussis-prn: 0.60, 0.37–0.98; pertussis-ptx: 0.66, 0.47–0.95), mumps and rubella 1-3y after first vaccination (0.73, 0.55–0.97; 0.70, 0.55–0.90), and rubella 1 m-1y after second vaccination (0.83, 0.55–0.90)). After adjustment for multiple testing, none of the differences remained significant. There was no association between SES and proportion of children with protective IgG levels. ConclusionIn this explorative study, we found no consistent association between SES and immune response to vaccination in the Netherlands and no association with protective IgG levels. Additional studies in other settings should confirm this finding.

The Antibody Response Following a Booster With Either a 10- or 13-valent Pneumococcal Conjugate Vaccine in Toddlers Primed With a 13-valent Pneumococcal Conjugate Vaccine in Early Infancy.

Both the 13- and 10-valent pneumococcal conjugate vaccines (PCV-13; PCV-10) are immunogenic and effective against vaccine-type pneumococcal disease when given to young children. However, limited data are available regarding the interchangeability of these 2 vaccines. UK children (n = 178) who had previously been vaccinated with PCV-13 at 2 and 4 months were randomized to receive either a PCV-13 or a PCV-10 booster at 12 months of age. PCV-13 vaccine-type antipolysaccharide serum immunoglobulin G (IgG) concentrations and opsonophagocytic assay titers were measured before and at 1 and 12 months following vaccination. The primary objective was to assess noninferiority of PCV-10 compared with PCV-13. For 8 of the PCV-10 serotypes at least 97% of participants in both groups had IgG concentrations ≥0.35 µg/mL at 1 month after vaccination; inferior responses were seen for serotypes 5 and 9V following the PCV-10 compared with the PCV-13 booster. Post booster geometric mean IgG concentrations and opsonophagocytic assay titers were significantly superior for most serotypes in PCV-13 compared with PCV-10 recipients, whereas similar or inferior responses were seen for serotypes 4, 18C, and 19F. Although some increase in antibody was seen in PCV-10 recipients against the serotypes 6A and 19A (serotypes that cross-react with 6B and 19F in PCV-10, respectively) at 1-month post booster, these responses were significantly lower than in the PCV-13 group. In PCV-13 primed infants, a PCV-10 booster is generally less immunogenic than a PCV-13 booster. For the 3 serotypes in PCV-10 with higher antigen content and/or conjugation to diphtheria or tetanus toxoid carrier proteins, higher or similar booster responses were seen in PCV-10 recipients. Although these findings suggest that responses are generally better with a PCV-13 booster among PCV-13 primed children, the clinical significance of these differences in immunogenicity is unclear.

Population-Level Persistence of Immunity 2 Years After the PsA-TT Mass-Vaccination Campaign in Mali.

Background. In 2010, Africa's first preventive meningococcal mass vaccination campaign was launched using a newly developed Neisseria meningitidis group A (NmA) polysaccharide–tetanus toxoid conjugate vaccine, PsA-TT (MenAfriVac), designed specifically for the meningitis belt. Given PsA-TT's recent introduction, the duration of protection against meningococcal group A is unknown.Methods. We conducted a household-based, age-stratified seroprevalence survey in Bamako, Mali, in 2012, 2 years after the vaccination campaign targeted all 1- to 29-year-olds. Randomly selected participants who had been eligible for PsA-TT provided a blood sample and responded to a questionnaire. Sera were analyzed to assess NmA-specific serum bactericidal antibody titers using rabbit complement (rSBA) and NmA-specific immunoglobulin G (IgG) by enzyme-linked immunosorbent assay. The proportion of participants putatively protected and the age group- and sex-specific rSBA geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) were determined.Results. Two years postvaccination, nearly all of the 800 participants (99.0%; 95% confidence interval [CI], 98.3%–99.7%) maintained NmA-specific rSBA titers ≥8, the accepted threshold for protection; 98.6% (95% CI, 97.8%–99.4%) had titers ≥128, and 89.5% (95% CI, 87.4%–91.6%) had titers ≥1024. The rSBA GMTs were significantly higher in females than in males aged <18 years at vaccination (P < .0001). NmA-specific IgG levels ≥2 µg/mL were found in 88.5% (95% CI, 86.3%–90.7%) of participants.Conclusions. Two years after PsA-TT introduction, a very high proportion of the population targeted for vaccination maintains high antibody titers against NmA. Assessing the duration of protection provided by PsA-TT is a priority for implementing evidence-based vaccination strategies. Representative, population-based seroprevalence studies complement clinical trials and provide this key evidence.

IgG levels against 13-valent pneumococcal conjugate vaccine serotypes in non pneumococcal conjugate vaccine immunized healthy Japanese and intravenous immunoglobulin preparations.

No studies showed specific antibody levels against all serotypes covered by 13-valent pneumococcal conjugate vaccine (PCV13) among polyclonal intravenous immunoglobulin (IVIG) products. Our study aimed to assess whether we could expect the efficacy of IVIG therapy for invasive pneumococcal disease (IPD) and to clarify the age group which should be recommended for IVIG therapy in case of IPD. Serotype-specific immunoglobulin G (IgG) levels against PCV13 serotypes were measured in four IVIGs which were produced from Japanese donors who were not immunized with any pneumococcal conjugate vaccines (PCVs), and in the serum of 160 non-PCV immunized Japanese subjects, by enzyme-linked immunosorbent assay. The functional opsonic activities of the IVIGs against serotypes 6B and 19A were assessed by a multiplexed opsonophagocytic killing assay. Japanese infants aged <2 years had a geometric mean IgG concentration of <0.35 μg/ml against several serotypes. Serotype-specific IgG concentrations varied among IVIGs. In general, IgG antibodies against serotypes 6A, 14 and 19A were higher in each IVIG. Although opsonization indices also varied among preparations, each IVIG had the ability to opsonize both serotypes 6B and 19A. This study suggests that routine immunization with PCV is important for prevention of IPD, especially for children <2 years old and IVIGs might be effective for IPD patients.

Immunogenicity and safety of CRM 197 conjugated 9-valent pneumococcal and meningococcal C combination vaccine in healthy infants

Streptococcus pneumoniae and Neisseria meningitidis cause invasive disease in children aged <2 years. While individual conjugate vaccines are available to protect this age group against these pathogens, availability of a vaccine combining these antigens into a single injection is desirable. This study randomized 467 healthy infants to receive 4 doses of combination 9-valent pneumococcal and meningococcal serogroup C conjugate vaccine (9vPnC-MnCC) or 9-valent pneumococcal conjugate vaccine (9vPnC). Percentages of subjects achieving immunoglobulin G (IgG) antibody concentrations ≥0.35 μg/mL and geometric mean IgG concentrations for each pneumococcal serotype in the 9vPnC-MnCC group were noninferior compared to the 9vPnC group. Both vaccines were well-tolerated.

Immunogenicity and Reactogenicity of Pneumococcal Polysaccharide and Conjugate Vaccines in Alaska Native Adults 55–70 Years of Age

Vaccination with conjugate vaccines stimulates T cell-dependent immunity, whereas vaccination with polysaccharide vaccines does not. Thus, vaccination with the 7-valent pneumococcal conjugate vaccine (PCV7) followed by the 23-valent pneumococcal polysaccharide vaccine (PPV23) may offer better protection against invasive pneumococcal disease for older adults than does vaccination with PPV23 alone, which is what is currently recommended. Alaska Native adults 55-70 years of age with no previous pneumococcal vaccination were randomized to receive (1) PPV23, (2) PCV7 followed 2 months later by PPV23, or (3) PCV7 followed 6 months later by PPV23. Participants recorded reactions after each vaccination. Serum samples collected during the period from May 2002 through February 2003 were tested for serotype-specific immunoglobulin G (IgG) and for opsonophagocytic activity (OPA) against serotypes 1, 4, 6B, 14, and 19F. Vaccination with PCV7 was well tolerated, but persons receiving PCV7 followed by PPV23 reported more local reactions than those receiving only PPV23. All reactions resolved spontaneously within 72 h of receiving vaccine. The geometric mean IgG concentrations of and the median OPA titers to serotypes 4, 6B, 14, and 19F increased in all groups after 1 dose of either PCV7 or PPV23. Serotype-specific geometric mean IgG concentrations and median OPA titers did not differ between any of the groups after vaccination with PPV23, regardless of whether they had previously received PCV7. In this study, PCV7 given 2 or 6 months before PPV23 was well tolerated but did not improve immune response to PPV23 in older Alaska Native adults.

Multiple‐dose granulocyte‐macrophage–colony‐stimulating factor plus 23‐valent polysaccharide pneumococcal vaccine in patients with chronic lymphocytic leukemia

For the current study, the authors sought to determine whether administration of multiple-dose granulocyte-macrophage-colony-stimulating factor (GM-CSF) could improve response to standard 23-valent polysaccharide pneumococcal vaccine (PPV) in patients with chronic lymphocytic leukemia (CLL). Patients were allocated randomly to receive PPV either alone or with 3 doses of GM-CSF (250 microg) given before or after vaccination. Serum was obtained before, 4 weeks after, and 12 weeks after vaccination for antibody determination. Thirty-two patients with CLL were given PPV. They were randomized to receive 3 doses of GM-CSF either before or after vaccination or to receive no GM-CSF. A 4-fold rise in immunoglobulin G (IgG) to capsular polysaccharides from Streptococcus pneumoniae types 4, 6B, 9V, 14, 19F, and 23F occurred in <10% of patients in each of the 3 groups. There were no differences in geometric mean IgG levels in any of the 3 groups 4 weeks or 12 weeks after vaccination. In patients with CLL, the response to pure polysaccharide pneumococcal vaccine was low despite immune enhancement with multiple doses of GM-CSF. In all patients, reactogenicity was minor.

A blinded, randomized, multicenter study of an intravenous Staphylococcus aureus immune globulin

Very low birth weight (VLBW) infants are vulnerable to nosocomial infections and subsequent morbidity; including infections caused by Staphylococcus aureus: 85% of nosocomial S. aureus infections are caused by capsular polysaccharide (CPS) types 5 and 8. Altastaph is a polyclonal investigational human immunoglobulin G (IgG) with high levels of opsonizing S. aureus CPS types 5 and 8 IgG. A Phase 2 clinical trial to assess the safety and kinetics of Altastaph in VLBW infants. Neonates in this multicenter study were randomized to receive two identical 20 ml/kg i.v. infusions of either 0.45% NaCl placebo or 1000 mg Altastaph/kg. Each infant was followed for 28 days after the second infusion or until discharge. Serum S. aureus CPS types 5 and 8 IgG levels were measured preinfusion and at various times after each infusion. Of 206 neonates, 158 received both infusions. Adverse events were similar in the two treatment groups. Six subjects (3% in each group) discontinued owing to an adverse event. Geometric mean anti-type 5 IgG levels were 402 and 642 mcg/ml 1 day following infusion of the first (day 0) and Second (day 14) doses, respectively, in neonates < or =1000 g and slightly higher in neonates 1001 to 1500 g. Trough levels before second infusion were 188 mcg/ml. Type 8 IgG levels were similar. Geometric mean IgG levels among placebo recipients were consistently <2 and <5 mcg/ml for types 5 and 8 in both weight groups. Three episodes of S. aureus bacteremia occurred in each arm. Infusion of Altastaph in VLBW neonates resulted in high levels of specific S. aureus types 5 and 8 CPS IgG. The administration of this anti-staphylococcal hyperimmune globulin was well tolerated in this population.

Effect of Dosage on Immunogenicity of a Vi Conjugate Vaccine Injected Twice into 2- to 5-Year-Old Vietnamese Children

In a double-blind, randomized, and placebo-controlled previous trial, the efficacy of Vi-rEPA for typhoid fever in 2- to 5-year-olds was 89.0% for 46 months. Vi-rEPA contained 25 microg of Vi and induced a greater-than-eightfold rise in immunoglobulin G (IgG) anti-Vi in all of the vaccinees tested. In this investigation, we conducted a dosage-immunogenicity study of 5, 12.5, and 25 microg of Vi-rEPA in this age group. Two doses of Vi-rEPA were injected 6 weeks apart. Blood samples were taken before and at 10 weeks (4 weeks after the second injection) and 1 year later. All postimmunization geometric mean (GM) levels were higher than the preimmune levels (P < 0.0001). At 10 weeks, the GM IgG anti-Vi level elicited by 25 microg (102 EU/ml) was higher than those elicited by 12.5 microg (74.7 EU/ml) and 5 microg (43 EU/ml) (P < 0.004): all of the children had > or = 3.52 EU/ml (estimated minimum protective level). One year later, the levels declined about sevenfold (13.3 and 11.3 versus 6.43 EU/ml, P < 0.0001) but remained significantly higher than the preimmune levels (P < 0.0001), and >96% of the children had a greater-than-eightfold rise. This study also confirmed the safety and consistent immunogenicity of the four lots of Vi-rEPA used in this and previous trials.

Preparation and characterization of group A meningococcal capsular polysaccharide conjugates and evaluation of their immunogenicity in mice.

Epidemic and endemic meningitis caused by group A Neisseria meningitidis remains a problem in sub-Saharan Africa. Although group A meningococcal capsular polysaccharide (GAMP) vaccine confers immunity at all ages, the improved immunogenicity of a conjugate and its compatibility with the World Health Organization's Extended Program on Immunization offers advantages over GAMP alone. Conjugates of GAMP bound to bovine serum albumin (BSA) were synthesized, characterized, and evaluated for their immunogenicities in mice. Two methods, involving adipic acid dihydrazide (ADH) as a linker, were used. First, ADH was bound to GAMP activated with cyanogen bromide (CNBr) or with 1-cyano-4(dimethylamino)-pyridinium tetrafluoroborate (CDAP) to form GAMP(CNBr)AH and GAMP(CDAP)AH. These derivatives were bound to BSA by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) to form GAMP(CNBr)AH-BSA and GAMP(CDAP)AH-BSA. Second, ADH was bound to BSA with EDC to form AHBSA. AHBSA was bound to activated GAMP to form GAMP(CNBr)-AHBSA and GAMP(CDAP)-AHBSA. The yield of GAMP(CDAP)-AHBSA (35 to 40%) was higher than those of the other conjugates (5 to 20%). GAMP conjugates elicited immunoglobulin G (IgG) anti-GAMP in all mice after three injections of 2.5 or 5.0 microg of GAMP: the geometric mean (GM) was highest in recipients of GAMP(CDAP)-AHBSA (11.40 enzyme-linked immunosorbent assay units). Although the difference was not statistically significant, the 5.0- microg dose elicited a higher GM IgG anti-GAMP than the 2.5- microg dose. Low levels of anti-GAMP were elicited by GAMP alone. GAMP(CDAP)-AHBSA elicited bactericidal activity roughly proportional to the level of IgG anti-GAMP.