Acellular and Whole-Cell Pertussis Vaccines as Booster Doses: A Multicenter Study

PEDIATRICS ◽  
1994 ◽  
Vol 93 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Janet A. Englund ◽  
Michael D. Decker ◽  
Kathryn M. Edwards ◽  
Michael E. Pichichero ◽  
Mark C. Steinhoff ◽  
...  
Keyword(s):  
Public Health ◽  
Antibody Response ◽  
Multicenter Study ◽  
Adverse Reactions ◽  
Pain Medication ◽  
Antibody Responses ◽  
Whole Cell ◽  
Acellular Vaccines ◽  
Antibody Levels ◽  
Better Than

Objective. To compare the safety and immunogenicity of a variety of acellular (AC) and whole-cell (WC) pertussis vaccines combined with diphtheria and tetanus toxoids. Methods. Standard enrollment and reaction forms were used at five sites, and serologic evaluation was performed at a single site. Nine AC (Massachusetts Public Health Laboratories, Biocine Sclavo recombinant pertussis toxoid [PT], Connaught/BIKEN, Lederle three-component, Biocine Sclavo recombinant three-component, SmithKline Beecham three-component, Porton three-component, Takeda-Wyeth, and Connaught multicomponent), and three WC (Connaught Laboratoties, Lederle Laboratories, and Massachusetts Public Health Laboratories) were studied. All AC contained varying concentrations of PT; some vaccines also contamed filamentous hemagglutinin (FHA), pertactin, and/or agglutinogens. Results. Two hundred forty children, aged 16 to 21 months and 4 to 6 years, were enrolled at five sites. Significantly less fever, redness, swelling, pain, limp, and use of pain medication were noted following AC compared with WC. Significant increases in antibody to PT were seen following all vaccines. Significant rises in FHA antibody were seen following all WC and the seven AC that contained FHA. Postbooster PT antibody levels were similar among the AC groups, regardless of the amount of PT administered (between 3.5 and 25 µg per dose). The dose of FHA did not affect PT antibody response. Infants primed with WC who were boosted with a monocomponent PT vaccine did not manifest a significant antibody response to FHA. Conclusion. The rate of adverse reactions was not a function of the number of antigens or the antigen quantity in the acellular vaccines, and antibody responses following AC were similar or better than antibody responses following WC. These results support the further evaluation of these vaccines in a larger National Institute of Allergy and Infectious Diseases-sponsored study in infants.

scholarly journals Mucosal versus systemic antibody responses to SARS-CoV-2 antigens in COVID-19 patients

2020 ◽  
Author(s):  
Baweleta Isho ◽  
Kento T Abe ◽  
Michelle Zuo ◽  
Alainna J Jamal ◽  
Bhavisha Rathod ◽  
...  
Keyword(s):  
Antibody Response ◽  
Upper Airway ◽  
Mucosal Immune Response ◽  
Antibody Responses ◽  
Igg Antibodies ◽  
Blood Draw ◽  
Neutralization Activity ◽  
Surrogate Measure ◽  
Antibody Levels ◽  
Negative Controls

While the antibody response to SARS-CoV-2 has been extensively studied in blood, relatively little is known about the mucosal immune response and its relationship to systemic antibody levels. Since SARS-CoV-2 initially replicates in the upper airway, the antibody response in the oral cavity is likely an important parameter that influences the course of infection, but how it correlates to the antibody response in serum is not known. Here, we profile by enzyme linked immunosorbent assays (ELISAs) IgG, IgA and IgM responses to the SARS-CoV-2 spike protein (full length trimer) and its receptor binding domain (RBD) in serum (n=496) and saliva (n=90) of acute and convalescent patients with laboratory-diagnosed COVID-19 ranging from 3-115 days post-symptom onset (PSO), compared to negative controls. Anti-CoV-2 antibody responses were readily detected in serum and saliva, with peak IgG levels attained by 16-30 days PSO. Whereas anti-CoV-2 IgA and IgM antibodies rapidly decayed, IgG antibodies remained relatively stable up to 105 days PSO in both biofluids. In a surrogate neutralization ELISA (snELISA), neutralization activity peaks by 31-45 days PSO and slowly declines, though a clear drop is detected at the last blood draw (105-115 days PSO). Lastly, IgG, IgM and to a lesser extent IgA responses to spike and RBD in the serum positively correlated with matched saliva samples. This study confirms that systemic and mucosal humoral IgG antibodies are maintained in the majority of COVID-19 patients for at least 3 months PSO. Based on their correlation with each other, IgG responses in saliva may serve as a surrogate measure of systemic immunity.

scholarly journals More rapid, robust and sustainable antibody responses to mRNA COVID-19 vaccine in convalescent COVID-19 individuals

2021 ◽  
Author(s):  
Sabrina E Racine-Brzostek ◽  
Jim Yee ◽  
Ashley Sukhu ◽  
Yuqing Qiu ◽  
Sophie Rand ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Antibody Response ◽  
Real World ◽  
Neutralizing Antibodies ◽  
Vaccine Dose ◽  
Antibody Responses ◽  
Antibody Levels

Longitudinal studies are needed to evaluate the SARS-CoV-2 mRNA vaccine antibody response under real-world conditions. This longitudinal study investigated the quantity and quality of SARS-CoV-2 antibody response in 846 specimens from 350 subjects: comparing BNT162b2-vaccinated individuals (19 previously diagnosed with COVID-19 [RecoVax]; 49 never been diagnosed [NaiveVax]) to 122 hospitalized unvaccinated (HospNoVax) and 160 outpatient unvaccinated (OutPtNoVax) COVID-19 patients. NaiveVax experienced a delay in generating SARS-CoV-2 total antibody levels (TAb) and neutralizing antibodies (SNAb) after the 1st vaccine dose (D1), but a rapid increase in antibody levels was observed after the 2nd dose (D2). However, these never reached the robust levels observed in RecoVax. In fact, NaiveVax TAb and SNAb levels decreased 4-weeks post-D2 (p=0.003;p<0.001). For the most part, RecoVax TAb persisted throughout this study, after reaching maximal levels 2-weeks post-D2; but SNAb decreased significantly ~6-months post-D1 (p=0.002). Although NaiveVax avidity lagged behind that of RecoVax for most of the follow-up periods, NaiveVax did reach similar avidity by ~6-months post-D1. These data suggest that one vaccine dose elicits maximal antibody response in RecoVax and may be sufficient. Also, despite decreasing levels in TAb and SNAb overtime, long-term avidity maybe a measure worth evaluating and possibly correlating to vaccine efficacy.

scholarly journals Antibody Responses in Elderly Residential Care Persons following COVID-19 mRNA Vaccination

2021 ◽  
Author(s):  
David A Nace ◽  
Kevin E Kip ◽  
Octavia M Peck Palmer ◽  
Michael R Shurin ◽  
Katie Mulvey ◽  
...  
Keyword(s):  
Antibody Response ◽  
Assisted Living ◽  
Independent Living ◽  
Long Term Care ◽  
Linear Regression Analysis ◽  
Antibody Responses ◽  
Personal Care ◽  
Term Care ◽  
Antibody Levels

Objective COVID-19 disproportionately impacts older adults residing at long-term care facilities. Data regarding antibody response to COVID-19 vaccines in this population is limited. Our objective was to quantify the presence and magnitude of antibody response in older, vaccinated residents at assisted living, personal care, and independent living facilities. Design A cross-sectional quality improvement study was conducted March 15-April 1, 2021 in the Pittsburgh region. Setting and Population Participants were volunteers at assisted living, personal care, and independent living facilities, who received mRNA COVID-19 vaccine. Conditions that obviate immune responses were exclusionary criteria. Methods Sera were collected to measure IgG anti-SARS-CoV-2 antibody level with reflex to total anti-SARS-CoV-2 immunoglobulin levels. Descriptive statistics, Pearson correlation coefficients, and multiple linear regression analysis were performed to evaluate relationships between factors potentially associated with antibody levels. Results All participants (N=70) had received two rounds of vaccination for COVID-19 and were found to have antibodies to SARS-CoV-2. There was wide variation in relative levels of antibodies as determined by extinction coefficients. Antibody levels trended lower in male sex, advanced age, steroid medications, and longer length of time from vaccination. Conclusions and Implications Higher functioning long-term care residents mounted detectable antibody responses when vaccinated with COVID-19 mRNA-based vaccines. This study provides preliminary information on level of population risk of assisted living, personal care, and independent living residents which can inform reopening strategies. Data suggests some degree of immunity is present during the immediate period following vaccination. However, protective effects of such vaccination programs remain to be determined in larger studies. Clinical protection is afforded not just by pre-formed antibody levels, but by ongoing adaptive immunity, which is known to be decreased in older individuals. Thus, the implications of these levels of antibodies in preventing COVID-19 disease must be determined by clinical follow-up.

scholarly journals Neutralizing antibody response in non-hospitalized SARS-CoV-2 patients

2020 ◽  
Author(s):  
Natalia Ruetalo ◽  
Ramona Businger ◽  
Karina Althaus ◽  
Simon Fink ◽  
Felix Ruoff ◽  
...  
Keyword(s):  
Antibody Response ◽  
Western Blot ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Virus Neutralization ◽  
Surrogate Markers ◽  
High Antibody ◽  
Serological Survey ◽  
Course Of Disease ◽  
Antibody Levels

The majority of infections with SARS-CoV-2 are asymptomatic or mild without the necessity of hospitalization. It is of importance to reveal if these patients develop an antibody response against SARS-CoV-2 and to define which antibodies confer virus neutralization. We conducted a comprehensive serological survey of 49 patients with a mild course of disease and quantified neutralizing antibody responses against a clinical SARS-CoV-2 isolate employing human cells as targets. Four patients (8%), even though symptomatic, did not develop antibodies against SARS-CoV-2 and two other patients (4%) were only positive in one of the six serological assays employed. For the remainder, antibody response against the S-protein correlated with serum neutralization whereas antibodies against the nucleocapsid were poor predictors of virus neutralization. Regarding neutralization, only six patients (12%) could be classified as highly neutralizers. Furthermore, sera from several individuals with fairly high antibody levels had only poor neutralizing activity. In addition, employing a novel serological Western blot system to characterize antibody responses against seasonal coronaviruses, we found that antibodies against the seasonal coronavirus 229E might contribute to SARS-CoV-2 neutralization. Altogether, we show that there is a wide breadth of antibody responses against SARS-CoV-2 in patients that differentially correlate with virus neutralization. This highlights the difficulty to define reliable surrogate markers for immunity against SARS-CoV-2.

Comparison of 13 Acellular Pertussis Vaccines: Adverse Reactions

PEDIATRICS ◽  
1995 ◽  
Vol 96 (3) ◽  
pp. 557-566
Author(s):  
Michael D. Decker ◽  
Kathryn M. Edwards ◽  
Mark C. Steinhoff ◽  
Margaret B. Rennels ◽  
Michael E. Pichichero ◽  
...  
Keyword(s):  
Adverse Reactions ◽  
Cell Vaccine ◽  
Whole Cell ◽  
The Third ◽  
Efficacy Trials ◽  
Healthy Infants ◽  
Long Term Follow Up ◽  
Whole Cell Vaccine ◽  
Acellular Vaccines

Objective. To compare the reactogenicity of a licensed conventional whole-cell (WCL) and 13 acellular pertussis vaccines that differed in the source, manufacture, and quantity of included antigens; all vaccines included diphtheria and tetanus toxoids. Methods. Healthy infants were enrolled through six university-based vaccine and treatment evaluation units and were randomized to receive one of the study vaccines at 2, 4, and 6 months of age. Parents recorded the occurrence of fever, redness, swelling, pain, fussiness, drowsiness, anorexia, and use of antipyretics for 2 weeks after each inoculation; nurses interviewed parents on the third day and at each succeeding visit; long-term follow-up information was collected from parents and medical records 1 year after the third immunization. Results. Of 2200 vaccinated infants, 2189 contributed reaction data after 6375 vaccinations. For every acellular vaccine, every monitored reaction except vomiting occurred at a significantly lower frequency and severity than was seen with WCL. The groups receiving acellular pertussis vaccines differed significantly with respect to redness, swelling, pain, and vomiting, but not with respect to fussiness, antipyretic use, drowsiness, or anorexia. Conclusion. Although there were differences among the acellular vaccines, none was consistently the most or least reactogenic; all were associated with substantially fewer and less severe adverse reactions than a standard commercial whole-cell vaccine. Selection of acellular vaccines for further development and for introduction into efficacy trials can give priority to assessments of immunogenicity and purity, with comparative reactogenicity a secondary consideration.

scholarly journals Persistence of serum and saliva antibody responses to SARS-CoV-2 spike antigens in patients with COVID-19

2020 ◽  
Vol 5 (52) ◽  
pp. eabe5511
Author(s):  
Baweleta Isho ◽  
Kento T. Abe ◽  
Michelle Zuo ◽  
Alainna J. Jamal ◽  
Bhavisha Rathod ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Antibody Response ◽  
Receptor Binding ◽  
Antibody Responses ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Igg Antibodies ◽  
Surrogate Measure ◽  
Antibody Levels ◽  
Negative Controls

Although the antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been extensively studied in blood, relatively little is known about the antibody response in saliva and its relationship to systemic antibody levels. Here, we profiled by enzyme-linked immunosorbent assays (ELISAs) immunoglobulin G (IgG), IgA, and IgM responses to the SARS-CoV-2 spike protein (full-length trimer) and its receptor binding domain (RBD) in serum and saliva of acute and convalescent patients with laboratory-diagnosed coronavirus disease 2019 (COVID-19) ranging from 3 to 115 days postsymptom onset (PSO), compared with negative controls. Anti–SARS-CoV-2 antibody responses were readily detected in serum and saliva, with peak IgG levels attained by 16 to 30 days PSO. Longitudinal analysis revealed that anti–SARS-CoV-2 IgA and IgM antibodies rapidly decayed, whereas IgG antibodies remained relatively stable up to 105 days PSO in both biofluids. Last, IgG, IgM, and, to a lesser extent, IgA responses to spike and RBD in the serum positively correlated with matched saliva samples. This study confirms that serum and saliva IgG antibodies to SARS-CoV-2 are maintained in most of the patients with COVID-19 for at least 3 months PSO. IgG responses in saliva may serve as a surrogate measure of systemic immunity to SARS-CoV-2 based on their correlation with serum IgG responses.

scholarly journals Differing antibody responses toHaemophilus influenzaetype b after meningitis or epiglottitis

1996 ◽  
Vol 116 (1) ◽  
pp. 21-26 ◽  
Author(s):  
P. D. R. Johnson ◽  
M. Hanlon ◽  
D. Isaacs ◽  
G. L. Gilbert
Keyword(s):  
Antibody Response ◽  
Haemophilus Influenzae ◽  
Confidence Intervals ◽  
Age Differences ◽  
Geometric Mean ◽  
Invasive Disease ◽  
Antibody Responses ◽  
Type B ◽  
Convalescent Phase ◽  
Antibody Levels

SummaryTwo common forms of invasive disease due toHaemophilus influenzaetype b (Hib) are epiglottitis and meningitis. It is not known why some children develop epiglottitis and others meningitis. To examine the hypothesis that epiglottitis occurs in children who may have been previously exposed to Hib, and who would therefore exhibit a more vigorous antibody response in convalescence, we measured levels of antibody to Hib capsule in 92 children. Geometric mean convalescent-phase IgG, IgA, IgM and total antibody levels were significantly higher in 45 children with epiglottitis than in 47 with meningitis, even after adjustment for age differences (mean total antibody, 95% confidence intervals: meningitis 0·38, 0·34–0·43; epiglottitis: 2·25, 2·0–2·54 μg/ml). However, contrary to previous reports, a poor antibody response was only observed in a minority of children with meningitis; the antibody response of the majority was indistinguishable from that observed in children with epiglottitis.

scholarly journals Pre-vaccination and early B cell signatures predict antibody response to SARS-CoV-2 mRNA vaccine

2021 ◽  
Author(s):  
Lela Kardava ◽  
Nicholas Rachmaninoff ◽  
William Lau ◽  
Clarisa Buckner ◽  
Krittin Trihemasava ◽  
...  
Keyword(s):  
Antibody Response ◽  
B Cell ◽  
Response Variability ◽  
Antibody Responses ◽  
Igg Antibody ◽  
Memory B Cell ◽  
Post Vaccination ◽  
Highly Effective ◽  
Antibody Levels ◽  
Early Indicators

SARS-CoV-2 mRNA vaccines are highly effective, although weak antibody responses are seen in some individuals with correlates of immunity that remain poorly understood. Here we longitudinally dissected antibody, plasmablast, and memory B cell (MBC) responses to the two-dose Moderna mRNA vaccine in SARS-CoV-2-uninfected adults. Robust, coordinated IgA and IgG antibody responses were preceded by bursts of spike-specific plasmablasts after both doses, but earlier and more intensely after dose two. Distinct antigen-specific MBC populations also emerged post-vaccination with varying kinetics. We identified antigen non-specific pre-vaccination MBC and post-vaccination plasmablasts after dose one and their spike-specific counterparts early after dose two that correlated with subsequent antibody levels. These baseline and response signatures can thus provide early indicators of serological efficacy and explain response variability in the population.

scholarly journals Antibody response to SARS-CoV-2 infection in humans: A systematic review

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244126
Author(s):  
Nathan Post ◽  
Danielle Eddy ◽  
Catherine Huntley ◽  
May C. I. van Schalkwyk ◽  
Madhumita Shrotri ◽  
...  
Keyword(s):  
Public Health ◽  
Systematic Review ◽  
Antibody Response ◽  
Acute Phase ◽  
Symptom Onset ◽  
Disease Onset ◽  
Antibody Responses ◽  
Neutralising Antibodies ◽  
Antibody Dynamics ◽  
Over Time

Background Progress in characterising the humoral immune response to Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) has been rapid but areas of uncertainty persist. Assessment of the full range of evidence generated to date to understand the characteristics of the antibody response, its dynamics over time, its determinants and the immunity it confers will have a range of clinical and policy implications for this novel pathogen. This review comprehensively evaluated evidence describing the antibody response to SARS-CoV-2 published from 01/01/2020-26/06/2020. Methods Systematic review. Keyword-structured searches were carried out in MEDLINE, Embase and COVID-19 Primer. Articles were independently screened on title, abstract and full text by two researchers, with arbitration of disagreements. Data were double-extracted into a pre-designed template, and studies critically appraised using a modified version of the Public Health Ontario Meta-tool for Quality Appraisal of Public Health Evidence (MetaQAT) tool, with resolution of disagreements by consensus. Findings were narratively synthesised. Results 150 papers were included. Most studies (113 or 75%) were observational in design, were based wholly or primarily on data from hospitalised patients (108, 72%) and had important methodological limitations. Few considered mild or asymptomatic infection. Antibody dynamics were well described in the acute phase, up to around three months from disease onset, but the picture regarding correlates of the antibody response was inconsistent. IgM was consistently detected before IgG in included studies, peaking at weeks two to five and declining over a further three to five weeks post-symptom onset depending on the patient group; IgG peaked around weeks three to seven post-symptom onset then plateaued, generally persisting for at least eight weeks. Neutralising antibodies were detectable within seven to 15 days following disease onset, with levels increasing until days 14–22 before levelling and then decreasing, but titres were lower in those with asymptomatic or clinically mild disease. Specific and potent neutralising antibodies have been isolated from convalescent plasma. Cross-reactivity but limited cross-neutralisation with other human coronaviridae was reported. Evidence for protective immunity in vivo was limited to small, short-term animal studies, showing promising initial results in the immediate recovery phase. Conclusions Literature on antibody responses to SARS-CoV-2 is of variable quality with considerable heterogeneity of methods, study participants, outcomes measured and assays used. Although acute phase antibody dynamics are well described, longer-term patterns are much less well evidenced. Comprehensive assessment of the role of demographic characteristics and disease severity on antibody responses is needed. Initial findings of low neutralising antibody titres and possible waning of titres over time may have implications for sero-surveillance and disease control policy, although further evidence is needed. The detection of potent neutralising antibodies in convalescent plasma is important in the context of development of therapeutics and vaccines. Due to limitations with the existing evidence base, large, cross-national cohort studies using appropriate statistical analysis and standardised serological assays and clinical classifications should be prioritised.

scholarly journals Obesity Outweighs Protection Conferred by Adjuvanted Influenza Vaccination

mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
Erik A. Karlsson ◽  
Tomer Hertz ◽  
Cydney Johnson ◽  
Andrew Mehle ◽  
Florian Krammer ◽  
...  
Keyword(s):  
Public Health ◽  
Influenza Virus ◽  
High Risk ◽  
Influenza Virus Infection ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Obese Mice ◽  
Virus Challenge ◽  
Obesity Epidemic ◽  
Antibody Levels

ABSTRACT Obesity is a risk factor for developing severe influenza virus infection, making vaccination of utmost importance for this high-risk population. However, vaccinated obese animals and adults have decreased neutralizing antibody responses. In these studies, we tested the hypothesis that the addition of either alum or a squalene-based adjuvant (AS03) to an influenza vaccine would improve neutralizing antibody responses and protect obese mice from challenge. Our studies demonstrate that adjuvanted vaccine does increase both neutralizing and nonneutralizing antibody levels compared to vaccine alone. Although obese mice mount significantly decreased virus-specific antibody responses, both the breadth and the magnitude of the responses against hemagglutinin (HA) and neuraminidase (NA) are decreased compared to the responses in lean mice. Importantly, even with a greater than fourfold increase in neutralizing antibody levels, obese mice are not protected against influenza virus challenge and viral loads remain elevated in the respiratory tract. Increasing the antigen dose affords no added protection, and a decreasing viral dose did not fully mitigate the increased mortality seen in obese mice. Overall, these studies highlight that, while the use of an adjuvant does improve seroconversion, vaccination does not fully protect obese mice from influenza virus challenge, possibly due to the increased sensitivity of obese animals to infection. Given the continued increase in the global obesity epidemic, our findings have important implications for public health. IMPORTANCE Vaccination is the most effective strategy for preventing influenza virus infection and is a key component for pandemic preparedness. However, vaccines may fail to provide optimal protection in high-risk groups, including overweight and obese individuals. Given the worldwide obesity epidemic, it is imperative that we understand and improve vaccine efficacy. No work to date has investigated whether adjuvants increase the protective capacity of influenza vaccines in the obese host. In these studies, we show that adjuvants increased the neutralizing and nonneutralizing antibody responses during vaccination of lean and obese mice to levels considered “protective,” and yet, obese mice still succumbed to infection. This vulnerability is likely due to a combination of factors, including the increased susceptibility of obese animals to develop severe and even lethal disease when infected with very low viral titers. Our studies highlight the critical public health need to translate these findings and better understand vaccination in this increasing population.

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