The duration, dynamics and determinants of SARS-CoV-2 antibody responses in individual healthcare workers

Abstract Background SARS-CoV-2 IgG antibody measurements can be used to estimate the proportion of a population exposed or infected and may be informative about the risk of future infection. Previous estimates of the duration of antibody responses vary. Methods We present 6 months of data from a longitudinal seroprevalence study of 3276 UK healthcare workers (HCWs). Serial measurements of SARS-CoV-2 anti-nucleocapsid and anti-spike IgG were obtained. Interval censored survival analysis was used to investigate the duration of detectable responses. Additionally, Bayesian mixed linear models were used to investigate anti-nucleocapsid waning. Results Anti-spike IgG levels remained stably detected after a positive result, e.g., in 94% (95% credibility interval, CrI, 91-96%) of HCWs at 180 days. Anti-nucleocapsid IgG levels rose to a peak at 24 (95% credibility interval, CrI 19-31) days post first PCR-positive test, before beginning to fall. Considering 452 anti-nucleocapsid seropositive HCWs over a median of 121 days from their maximum positive IgG titre, the mean estimated antibody half-life was 85 (95%CrI, 81-90) days. Higher maximum observed anti-nucleocapsid titres were associated with longer estimated antibody half-lives. Increasing age, Asian ethnicity and prior self-reported symptoms were independently associated with higher maximum anti-nucleocapsid levels and increasing age and a positive PCR test undertaken for symptoms with longer anti-nucleocapsid half-lives. Conclusion SARS-CoV-2 anti-nucleocapsid antibodies wane within months, and faster in younger adults and those without symptoms. However, anti-spike IgG remains stably detected. Ongoing longitudinal studies are required to track the long-term duration of antibody levels and their association with immunity to SARS-CoV-2 reinfection.

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The duration, dynamics and determinants of SARS-CoV-2 antibody responses in individual healthcare workers

10.1101/2020.11.02.20224824 ◽

2020 ◽

Cited By ~ 1

Author(s):

Sheila F Lumley ◽

Jia Wei ◽

Denise O’Donnell ◽

Nicole E Stoesser ◽

Philippa C Matthews ◽

...

Keyword(s):

Healthcare Workers ◽

Linear Models ◽

Asymptomatic Infection ◽

Antibody Responses ◽

Mixed Linear Models ◽

Igg Antibody ◽

Younger Adults ◽

Asian Ethnicity ◽

Antibody Levels ◽

Pcr Test

AbstractBackgroundSARS-CoV-2 IgG antibody measurements can be used to estimate the proportion of a population exposed or infected and may be informative about the risk of future infection. Previous estimates of the duration of antibody responses vary.MethodsWe present 6 months of data from a longitudinal seroprevalence study of 3217 UK healthcare workers (HCWs). Serial measurements of IgG antibodies to SARS-CoV-2 nucleocapsid were obtained. Bayesian mixed linear models were used to investigate antibody waning and associations with age, gender, ethnicity, previous symptoms and PCR results.ResultsIn this cohort of working age HCWs, antibody levels rose to a peak at 24 (95% credibility interval, CrI 19-31) days post-first positive PCR test, before beginning to fall. Considering 452 IgG seropositive HCWs over a median of 121 days (maximum 171 days) from their maximum positive IgG titre, the mean estimated antibody half-life was 85 (95%CrI, 81-90) days. The estimated mean time to loss of a positive antibody result was 137 (95%CrI 127-148) days. We observed variation between individuals; higher maximum observed IgG titres were associated with longer estimated antibody half-lives. Increasing age, Asian ethnicity and prior self-reported symptoms were independently associated with higher maximum antibody levels, and increasing age and a positive PCR test undertaken for symptoms with longer antibody half-lives.ConclusionIgG antibody levels to SARS-CoV-2 nucleocapsid wane within months, and faster in younger adults and those without symptoms. Ongoing longitudinal studies are required to track the long-term duration of antibody levels and their association with immunity to SARS-CoV-2 reinfection.SummarySerially measured SARS-CoV-2 anti-nucleocapsid IgG titres from 452 seropositive healthcare workers demonstrate levels fall by half in 85 days. From a peak result, detectable antibodies last a mean 137 days. Levels fall faster in younger adults and following asymptomatic infection.

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Humoral response to the BBIBP-CorV vaccine over time in healthcare workers with or without exposure to SARS-CoV-2

10.1101/2021.10.02.21264432 ◽

2021 ◽

Author(s):

María Noel Badano ◽

Florencia Sabbione ◽

Irene Keitelman ◽

Matias Pereson ◽

Natalia Aloisi ◽

...

Keyword(s):

Single Dose ◽

Sharp Increase ◽

Healthcare Workers ◽

Humoral Response ◽

Igg Antibody ◽

Antibody Titers ◽

Humoral Responses ◽

Antibody Levels ◽

Over Time

AbstractSARS-CoV-2-specific humoral response was analyzed over time in a group of healthcare workers with or without exposure to SARS-CoV-2, who underwent vaccination with BBIBP-CorV (Sinopharm) vaccine in Argentina.Seroconversion rates in unexposed subjects after the first and second doses were 40% and 100%, respectively, showing a significant increase in antibody concentrations from dose 1 to dose 2 (p<0.0001).The highest antibody concentrations were found in younger subjects and women, remaining significantly associated in a multivariable linear regression model (p=0.005).A single dose of the BBIBP-CorV vaccine induced a strong antibody response in individuals with prior SARS-CoV-2infection, while a second dose did not increase this response. A sharp increase in antibody concentrations was observed following SARS-CoV-2 infection in those participants who became infected after the first and second doses (p=0.008).Individuals with SARS-CoV-2 exposure prior to vaccination showed significantly higher anti-spike IgG antibody levels, at all-time points, than those not exposed (p<0.001). Higher antibody titers were induced by a single dose in previously SARS-CoV-2 infected individuals than those induced in naïve subjects by two doses of the vaccine (p<0.0001). Three months after the second dose both groups showed a decline in antibody levels, being more abrupt in unexposed subjects.Overall, our results showed a trend towards lower antibody concentrations over time following BBIBP-CorV vaccination. Sex and age seem to influence the magnitude of the humoral response in unexposed subjects while the combination of exposure to SARS-CoV-2 plus vaccination, whatever the sequence of the events was, produced a sharp increase in antibody levels.Evaluation of the humoral responses over time and the analysis of the induction and persistence of memory B and T cell responses, are needed to assess long-term immune protection induced by BBIBP-CorV vaccine.

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Viral Persistence Induces Antibody Inflation without Altering Antibody Avidity

Journal of Virology ◽

10.1128/jvi.03177-15 ◽

2016 ◽

Vol 90 (9) ◽

pp. 4402-4411 ◽

Cited By ~ 21

Author(s):

Suzanne P. M. Welten ◽

Anke Redeker ◽

René E. M. Toes ◽

Ramon Arens

Keyword(s):

B Cells ◽

Viral Persistence ◽

Antibody Responses ◽

Igg Antibody ◽

Antibody Avidity ◽

Follicular Helper ◽

Neutralizing Capacity ◽

Persistent Virus ◽

Antibody Levels

ABSTRACTAntibodies are implicated in long-term immunity against numerous pathogens, and because of this property, antibody induction is the basis for many vaccines. Little is known about the influence of viral persistence on the evolving antibody response. Here, we examined the characteristics of antibody responses to persistent infection by employing the prototypic betaherpesvirus family member cytomegalovirus (CMV) in experimental mouse models. During the course of infection, mouse CMV (MCMV)-specific IgM and IgG responses are elicited; however, IgG levels gradually inflate in the persistent phase of infection while IgM levels are stably maintained. Whereas CD27-CD70 interactions are dispensable, the CD28/B7 costimulatory pathway is critical for the class switching of MCMV-specific IgM-to-IgG B cell responses, which corresponds to the CD28/B7-dependent formation of CD4+T follicular helper cells (TFH) and germinal center (GC) B cells. Furthermore, the initial viral inoculum dose dictates the height of the antibody levels during IgG antibody inflation and relates to the induction of long-lived plasma cells and memory B cells. Antibody avidity nonetheless is not altered after the establishment of viral persistence and occurs independently of the inoculum doses. However, repetitive challenge with intact viral particles, accompanied by increased GC reactivity, promotes the development of high-avidity IgG responses with neutralizing capacity. These insights can be used for the rational design of CMV-based vaccines aimed at inducing antibody responses.IMPORTANCEAntibodies provide long-term protection to different pathogens. However, how antibody responses develop during persistent virus infection is not entirely clear. Here, we characterize factors that influence the virus-specific antibody response to persistent CMV. This study describes that during persistent infection, CMV-specific IgM antibody levels are stably maintained while IgG2b and IgG2c levels gradually inflate over time. In contrast, the IgG avidity remains similar after the establishment of viral persistence. The induction of T follicular helper cells and GC B cells requires CD4+T cell help and CD28/B7 costimulation signals and is essential for the development of CMV-specific IgG antibody responses. Furthermore, neutralizing CMV-specific antibodies appear to develop late after infection, yet the neutralizing capacity can be improved upon repetitive viral challenge that is associated with increased GC reactivity. The results described here could inform the use of CMV-based vaccines and may help to understand how our immune system copes with this persistent virus.

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Longitudinal Analysis of Cryptosporidium Species-Specific Immunoglobulin G Antibody Responses in Peruvian Children

Clinical and Vaccine Immunology ◽

10.1128/cvi.13.1.123-131.2006 ◽

2006 ◽

Vol 13 (1) ◽

pp. 123-131 ◽

Cited By ~ 43

Author(s):

Jeffrey W. Priest ◽

Caryn Bern ◽

Lihua Xiao ◽

Jacquelin M. Roberts ◽

James P. Kwon ◽

...

Keyword(s):

Immunoglobulin G ◽

Antibody Responses ◽

Health Interventions ◽

Older Children ◽

Serum Samples ◽

Igg Antibody ◽

Specific Immunoglobulin ◽

Antibody Assays ◽

Species Specific ◽

Antibody Levels

ABSTRACT Cryptosporidium species are ubiquitous in the environment and are frequently detected in the stools of children who live where sanitation conditions are poor. To better characterize the immune response to these parasites, we monitored immunoglobulin G (IgG) antibody levels in a cohort of children from Lima, Peru. Two new enzyme-linked immunosorbent assays based on the C. parvum (bovine, subtype IIa) Iowa strain 17-kDa and 27-kDa antigens were used to measure IgG antibody levels in longitudinal serum samples. Antibody responses were detected during infections with C. parvum, C. felis, and C. meleagridis and with four different subtypes of C. hominis. We also noted that the magnitude of the antibody response was related to the number of previous infections and that older children generally had higher levels of antibodies to the two C. parvum antigens. Antibody responses were not associated with infections with either Cyclospora sp. or Giardia sp. We believe the antibody assays will be important tools for monitoring the success of future public health interventions.

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

10.1101/2021.08.04.21261561 ◽

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.

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Reactogenicity Correlates Only Weakly with Humoral Immunogenicity after COVID-19 Vaccination with BNT162b2 mRNA (Comirnaty®)

Vaccines ◽

10.3390/vaccines9101063 ◽

2021 ◽

Vol 9 (10) ◽

pp. 1063

Author(s):

Jürgen Held ◽

Jan Esse ◽

Koray Tascilar ◽

Philipp Steininger ◽

Kilian Schober ◽

...

Keyword(s):

Linear Regression ◽

Regression Model ◽

Linear Regression Model ◽

Healthcare Workers ◽

Model Performance ◽

Neutralization Assay ◽

Spike Protein ◽

Igg Antibody ◽

Boost Vaccination ◽

Antibody Levels

mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), such as BNT162b2 (Comirnaty®), have proven to be highly immunogenic and efficient but also show marked reactogenicity, leading to adverse effects (AEs). Here, we analyzed whether the severity of AEs predicts the antibody response against the SARS-CoV-2 spike protein. Healthcare workers without prior SARS-CoV-2 infection, who received a prime-boost vaccination with BNT162b2, completed a standardized electronic questionnaire on the duration and severity of AEs. Serum specimens were collected two to four weeks after the boost vaccination and tested with the COVID-19 ELISA IgG (Vircell-IgG), the LIAISON® SARS-CoV-2 S1/S2 IgG CLIA (DiaSorin-IgG) and the iFlash-2019-nCoV NAb surrogate neutralization assay (Yhlo-NAb). A penalized linear regression model fitted by machine learning was used to correlate AEs with antibody levels. Eighty subjects were enrolled in the study. Systemic, but not local, AEs occurred more frequently after the boost vaccination. Elevated SARS-CoV-2 IgG antibody levels were measured in 92.5% of subjects with Vircell-IgG and in all subjects with DiaSorin-IgG and Yhlo-NAb. Gender, age and BMI showed no association with the antibody levels or with the AEs. The linear regression model identified headache, malaise and nausea as AEs with the greatest variable importance for higher antibody levels (Vircell-IgG and DiaSorin-IgG). However, the model performance for predicting antibody levels from AEs was very low for Vircell-IgG (squared correlation coefficient r2 = 0.04) and DiaSorin-IgG (r2 = 0.06). AEs did not predict the surrogate neutralization (Yhlo-NAb) results. In conclusion, AEs correlate only weakly with the SARS-CoV-2 spike protein antibody levels after COVID-19 vaccination with BNT162b2 mRNA.

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

10.1101/2021.04.07.21254925 ◽

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.

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Distinct age-specific SARS-CoV-2 IgG decay kinetics following natural infection

10.1101/2021.08.05.21259465 ◽

2021 ◽

Author(s):

Calvin P Sjaarda ◽

Emily Moslinger ◽

Kyla Tozer ◽

Robert I Colautti ◽

Samira Kheitan ◽

...

Keyword(s):

Natural Infection ◽

Decay Rates ◽

Decay Kinetics ◽

Serum Samples ◽

Igg Antibody ◽

Multi Centre Study ◽

Viral Neutralization ◽

Antibody Levels ◽

Over Time

Background. Antibody responses to SARS-CoV-2 can be observed as early as 14 days post- infection, but little is known about the stability of antibody levels over time. Here we evaluate the long-term stability of anti-SARS-CoV-2 IgG antibodies following infection in 402 adult donors. Methods. We performed a multi-centre study carried out at Plasma Donor Centres in the city of Heidelberg (Plasmazentrum Heidelberg, Germany) and Munich (Plasmazentrum M&uumlnchen, Germany). We present anti-S/N and anti-N IgG antibody levels in prospective serum samples collected up to 403 days post recovery from SARS-CoV-2 infected individuals. Results: The cohort includes 402 adult donors (185 female, 217 male; 17 - 68 years of age) where anti-SARS-CoV-2 IgG levels were measured in plasma samples collected between 18- and 403-days post SARS-CoV-2 infection. A linear mixed effects model demonstrated IgG decay rates that decrease over time (χ2=176.8, p<0.00001) and an interaction of time*age (χ2=10.0, p<0.005)), with those over 60+ years showing the highest baseline IgG levels and the fastest rate of IgG decay. Baseline viral neutralization assays demonstrated that serum IgG levels correlated with in vitro neutralization capacity in 91% of our cohort. Conclusion. Long-term antibody levels and age-specific antibody decay rates suggest the potential need for age-specific vaccine booster guidelines to ensure long term vaccine protection against SARS-CoV-2 infection.

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Can individuals with low antibody responses to vaccines against other viruses acquire adequate SARS-CoV-2 antibody after vaccination with the BNT162b2 mRNA vaccine?

10.1101/2021.12.26.21268358 ◽

2021 ◽

Author(s):

Wataru Ogura ◽

Kouki Ohtsuka ◽

Sachiko Matsuura ◽

Takahiro Okuyama ◽

Satsuki Matsushima ◽

...

Keyword(s):

Cohort Study ◽

Neutralizing Antibodies ◽

Healthcare Workers ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Antibody Activity ◽

Low Responders ◽

Before And After ◽

Positive Threshold ◽

Antibody Levels

Objective In Japan, healthcare workers (HCWs) are vaccinated against coronavirus disease (COVID-19) and other contagious viruses (measles, rubella, chickenpox, mumps, and hepatitis B) to prevent nosocomial infection. However, some do not produce sufficient antibodies after vaccination (low responders). This study investigated changes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels among HCWs after SARS-CoV-2 vaccination and assessed whether low responders produced adequate SARS-CoV-2 anti-spike and neutralizing antibodies. Methods We conducted a prospective cohort study of HCWs before and after vaccination with the BNT162b2 mRNA vaccine in a hospital in Tokyo, Japan. The HCWs received two doses of BNT162b2 vaccine, 3 weeks apart. Those whose antibody levels against previous antiviral vaccines did not reach protective antibody levels after receiving two doses were defined as low responders, whereas those who produced adequate antibodies were defined as normal responders. SARS-CoV-2 anti-spike antibodies were measured 11 times from before the first BNT162b2 vaccination to 5 months after the second vaccination. SARS-CoV-2 neutralizing antibody activity was measured twice in low responders, 1 week to 1 month and 5 months after the second vaccination. Results Fifty HCWs were included in the analytic cohort. After vaccination, SARS-CoV-2 anti-spike antibody was detectable in the samples from both responders at each timepoint, but the level was lower at 5 months than at 1 week after the second vaccination. Low responders had SARS-CoV-2 neutralizing antibody activity 1 week to 1 month after the second vaccination, which exceeded the positive threshold after 5 months. Conclusion After BNT162b2 vaccination, low responders acquired adequate SARS-CoV-2 anti-spike and SARS-CoV-2 neutralizing antibodies to prevent SARS-CoV-2. However, SARS-CoV-2 anti-spike antibody levels were lower at 5 months than at 1 week after the second dose of BNT162b2 vaccine in low and normal responders. Therefore, low responders should also receive a third dose of BNT162b2 vaccine.

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Specificity of Subcapsular Antibody Responses in Ethiopian Patients following Disease Caused by Serogroup A Meningococci

Clinical and Vaccine Immunology ◽

10.1128/cvi.00252-07 ◽

2008 ◽

Vol 15 (5) ◽

pp. 863-871 ◽

Cited By ~ 14

Author(s):

Gunnstein Norheim ◽

Abraham Aseffa ◽

Mohammed Ahmed Yassin ◽

Getahun Mengistu ◽

Afework Kassu ◽

...

Keyword(s):

Acute Phase ◽

Reference Strain ◽

Antibody Responses ◽

Enzyme Linked Immunosorbent Assay ◽

Human Antibody ◽

Igg Antibody ◽

Future Studies ◽

Antibody Specificities ◽

Antibody Levels

ABSTRACT Dissecting the specificities of human antibody responses following disease caused by serogroup A meningococci may be important for the development of improved vaccines. We performed a study of Ethiopian patients during outbreaks in 2002 and 2003. Sera were obtained from 71 patients with meningitis caused by bacteria of sequence type 7, as confirmed by PCR or culture, and from 113 Ethiopian controls. Antibody specificities were analyzed by immunoblotting (IB) against outer membrane antigen extracts of a reference strain and of the patients' own isolates and by enzyme-linked immunosorbent assay for immunoglobulin G (IgG) levels against lipooligosaccharide (LOS) L11 and the proteins NadA and NspA. IB revealed that the main antigens targeted were the proteins PorA, PorB, RmpM, and Opa/OpcA, as well as LOS. MenA disease induced significant increases in IgG against LOS L11 and NadA. The IgG levels against LOS remained elevated following disease, whereas the IgG anti-NadA levels returned to acute-phase levels in the late convalescent phase. Among adults, the anti-LOS IgG levels were similar in acute-phase patient sera as in control sera, whereas anti-NadA IgG levels were significantly higher in acute-phase sera than in controls. The IgG antibody levels against LOS and NadA correlated moderately but significantly with serum bactericidal activity against MenA strains. Future studies on immune response during MenA disease should take into account the high levels of anti-MenA polysaccharide IgG commonly found in the population and seek to clarify the role of antibodies against subcapsular antigens in protection against MenA disease.

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