Evaluation of antigen-detecting and antibody-detecting diagnostic test combinations for diagnosing melioidosis

Background Melioidosis, an infectious disease caused by Burkholderia pseudomallei, is endemic in many tropical developing countries and has a high mortality. Here we evaluated combinations of a lateral flow immunoassay (LFI) detecting B. pseudomallei capsular polysaccharide (CPS) and enzyme-linked immunosorbent assays (ELISA) detecting antibodies against hemolysin co-regulated protein (Hcp1) or O-polysaccharide (OPS) for diagnosing melioidosis. Methodology/Principal findings We conducted a cohort-based case-control study. Both cases and controls were derived from a prospective observational study of patients presenting with community-acquired infections and sepsis in northeast Thailand (Ubon-sepsis). Cases included 192 patients with a clinical specimen culture positive for B. pseudomallei. Controls included 502 patients who were blood culture positive for Staphylococcus aureus, Escherichia coli or Klebsiella pneumoniae or were polymerase chain reaction assay positive for malaria or dengue. Serum samples collected within 24 hours of admission were stored and tested using a CPS-LFI, Hcp1-ELISA and OPS-ELISA. When assessing diagnostic tests in combination, results were considered positive if either test was positive. We selected ELISA cut-offs corresponding to a specificity of 95%. Using a positive cut-off OD of 2.912 for Hcp1-ELISA, the combination of the CPS-LFI and Hcp1-ELISA had a sensitivity of 67.7% (130/192 case patients) and a specificity of 95.0% (477/502 control patients). The sensitivity of the combination (67.7%) was higher than that of the CPS-LFI alone (31.3%, p<0.001) and that of Hcp1-ELISA alone (53.6%, p<0.001). A similar phenomenon was also observed for the combination of CPS-LFI and OPS-ELISA. In case patients, positivity of the CPS-LFI was associated with a short duration of symptoms, high modified Sequential (sepsis-related) Organ Failure Assessment (SOFA) score, bacteraemia and mortality outcome, while positivity of Hcp1-ELISA was associated with a longer duration of symptoms, low modified SOFA score, non-bacteraemia and survival outcome. Conclusions/Significance A combination of antigen-antibody diagnostic tests increased the sensitivity of melioidosis diagnosis over individual tests while preserving high specificity. Point-of-care tests for melioidosis based on the use of combination assays should be further developed and evaluated.

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Clinical Evaluation of a COVID-19 Antibody Lateral Flow Assay using Point of Care Samples

10.1101/2020.12.02.20242750 ◽

2020 ◽

Author(s):

Won Lee ◽

Steven Straube ◽

Ryan Sincic ◽

Jeanne A. Noble ◽

Juan Carlos Montoy ◽

...

Keyword(s):

Predictive Value ◽

Point Of Care ◽

Acute Infection ◽

High Specificity ◽

Lateral Flow ◽

Lateral Flow Immunoassay ◽

Onset Date ◽

Rt Pcr ◽

Serum Samples ◽

Antibody Positivity

ABSTRACTIntroductionThe ongoing SARS-CoV-2 pandemic has spurred the development of numerous point of care (PoC) immunoassays. Assessments of performance of available kits are necessary to determine their clinical utility. Previous studies have mostly performed these assessments in a laboratory setting, which raises concerns of translating findings for PoC use. The aim of this study was to assess the performance of a lateral flow immunoassay for the detection of SARS-CoV-2 antibodies using samples collected at PoC.MethodOne lateral flow immunoassay (Humasis® COVID-19 IgG/IgM) was tested. In total, 50 PCR RT-PCR positive and 52 RT-PCR negative samples were collected at PoC. Fifty serum specimens from Dec 2018 to Feb 2019 were used as controls for specificity. Serum samples collected between Dec 2019 to Feb 2020 were used as additional comparators. Clinical data including symptom onset date was collected from patient history and the medical record.ResultsThe overall sensitivity for the kit was 74% (95% CI: 59.7% -85.4%). The sensitivity for IgM and IgG detection >14 days after date of onset was 88% (95% CI: 68.8% -97.5%) and 84% (95% CI: 63.9% – 95.5%), with a negative predictive value (NPV) of 94% for IgM (95% CI: 83.5% - 98.8%) and 93% for IgG (95% CI: 81.8% - 97.9%). The overall specificity was 94% (95% CI: 83.5% - 98.8%). The Immunoglobulin specific specificity was 94% for IgM (95% CI: 83.5% - 98.8%) and 98% for IgG (95% CI: 89.4% - 100.0%), with a positive predictive value (PPV) of 88% for IgM (95% CI: 68.8% - 97.5%) and 95% for IgG (95% CI: 77.2% - 99.9%) respectively for samples collected from patients >14 days after date of onset. Specimen collected during early phase of COVID-19 pandemic (Dec 2019 to Feb 2020) showed 11.8% antibody positivity, and 11.3% of PCR-negative patients demonstrated antibody positivity.DiscussionHumasis® COVID-19 IgG/IgM LFA demonstrates greater than 90% PPV and NPV for samples collected 14 days after the onset of symptoms using samples collected at PoC. While not practical for the diagnosis of acute infection, the use of the lateral flow assays with high specificity may have utility for determining seroprevalence or seroconversion in longitudinal studies.

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An origami paper-based nanoformulated immunosensor detects picograms of VEGF-C per milliliter of blood

Communications Biology ◽

10.1038/s42003-020-01607-8 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Shuai Sun ◽

Yang Wang ◽

Tao Ming ◽

Jinping Luo ◽

Yu Xing ◽

...

Keyword(s):

Limit Of Detection ◽

Point Of Care ◽

Clinical Importance ◽

High Specificity ◽

Tumor Biomarker ◽

Serum Samples ◽

Patients With Cancer ◽

Factor C ◽

Endothelial Growth Factor ◽

Walled Carbon Nanotubes

AbstractDetecting vascular endothelial growth factor C (VEGF-C), a kind of tumor biomarker, is of significant clinical importance in evaluating the prognosis of patients with cancer. However, laboratory analyses are usually not suitable for point-of-care testing because they are expensive and time consuming. In response to these challenges, we fabricated an origami paper-based microfluidic electrochemical device. To improve the specificity of VEGF-C detection, nanocomposites, synthesized by new methylene blue (NMB), amino-functional single-walled carbon nanotubes (NH2-SWCNTs), and gold nanoparticles (AuNPs), were used to modify the surface of working electrodes. Results of electrochemical detection showed that the immunosensor had excellent linearity, ranging from 0.01 to 100 ng mL−1 (R2 = 0.988), and the limit of detection was 10 pg mL−1. To confirm the high specificity of the device under real-world conditions, we evaluated the device using clinical serum samples from our hospital. The results demonstrated that the device had an excellent performance and could provide a platform for real-time detection of cancers.

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Evaluation of rapid diagnostic tests and conventional enzyme-linked immunosorbent assays to determine prior dengue infection

Journal of Travel Medicine ◽

10.1093/jtm/taz078 ◽

2019 ◽

Vol 26 (8) ◽

Cited By ~ 12

Author(s):

Matthew Bonaparte ◽

Lingyi Zheng ◽

Sanjay Garg ◽

Bruno Guy ◽

Yaniv Lustig ◽

...

Keyword(s):

Diagnostic Tests ◽

Point Of Care ◽

Dengue Infection ◽

Cross Reactivity ◽

Rapid Diagnostic Tests ◽

World Health ◽

Serum Samples ◽

West Nile ◽

Immunosorbent Assays ◽

Prevaccination Screening

Abstract Background In September 2018, the World Health Organization recommended that prevaccination screening be used with the tetravalent dengue vaccine (CYD-TDV), to ensure that only individuals with evidence of prior dengue infection (PDI) are vaccinated. Dengue rapid diagnostic tests (RDTs) would offer a potential solution for prevaccination screening at the point-of-care, but data on performance of available RDTs for identifying PDI are limited. We determined the suitability of four dengue RDTs and two conventional enzyme-linked immunosorbent assays (ELISAs) to identify PDI and evaluated cross-reactivity with co-circulating flaviviruses. Methods: Specificity was assessed using 534 dengue-negative [determined by 50% plaque reduction neutralization test (PRNT50)] serum samples from USA (n = 229) and dengue-endemic regions (n = 305). Sensitivity was assessed using 270 samples from recent (n = 90) or remote (n = 90) virologically confirmed prior dengue cases, and dengue PRNT50-positive samples (n = 90). Cross-reactivity was assessed in dengue-seronegative samples that were seropositive for yellow fever (n = 57), Japanese encephalitis (n = 37), West Nile (n = 59) or Zika (n = 41). Results: Dengue IgG RDTs and the Panbio ELISA exhibited favourable specificities (99–100%), higher than the Focus ELISA (95%). The RDTs had variable sensitivities (40–70%) that were lower than those of the ELISAs (≥90%). Cross-reactivity to other flaviviruses was low with RDTs (≤7%), but more significant with ELISAs (up to 51% for West Nile and 34% for Zika). No cross-reactivity to any of the four closely related flaviviruses was observed with the CTK Biotech RDT. For each SeroTest, sensitivity appeared similar in samples from individuals with recent (<13 months) vs remote (3–4 years) virologically confirmed PDI. Conclusions: In general, dengue IgG RDTs were found to be more specific and less cross-reactive than the ELISAs, but the latter were more sensitive for identifying PDI cases. Currently available RDTs could be temporizing tools for rapid and safe prevaccination screening until improved RDTs with increased sensitivity become available.

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Antibody tests in detecting SARS-CoV-2 infection: a meta-analysis

10.1101/2020.04.22.20074914 ◽

2020 ◽

Cited By ~ 9

Author(s):

Panagiota I Kontou ◽

Georgia G Braliou ◽

Niki L Dimou ◽

Georgios Nikolopoulos ◽

Pantelis G Bagos

Keyword(s):

Diagnostic Tests ◽

Point Of Care ◽

Meta Analysis ◽

High Specificity ◽

Enzyme Linked Immunosorbent Assay ◽

Lower Sensitivity ◽

Serological Tests ◽

Bivariate Method ◽

Acid Test ◽

Antibody Tests

SummaryBackgroundWith the emergence of SARS-CoV-2 and the associated Coronavirus disease 2019 (COVID-19), there is an imperative need for diagnostic tests that can identify the infection. Although Nucleic Acid Test (NAT) is considered to be the gold standard, serological tests based on antibodies could be very helpful. However, individual studies measuring the accuracy of the various tests are usually underpowered and inconsistent, thus, a comparison of different tests is needed.MethodsWe performed a systematic review and meta-analysis following the PRISMA guidelines. We conducted the literature search in PubMed, medRxiv and bioRxiv. For the statistical analysis we used the bivariate method for meta-analysis of diagnostic tests pooling sensitivities and specificities. We evaluated IgM and IgG tests based on Enzyme-linked immunosorbent assay (ELISA), Chemiluminescence Enzyme Immunoassays (CLIA), Fluorescence Immunoassays (FIA) and the point-of-care (POC) Lateral Flow Immunoassays (LFIA) that are based on immunochromatography.FindingsIn total, we identified 38 eligible studies that include data from 7,848 individuals. The analyses showed that tests using the S antigen are more sensitive than N antigen-based tests. IgG tests perform better compared to IgM ones, and show better sensitivity when the samples were taken longer after the onset of symptoms. Moreover, irrespective of the method, a combined IgG/IgM test seems to be a better choice in terms of sensitivity than measuring either antibody type alone. All methods yielded high specificity with some of them (ELISA and LFIA) reaching levels around 99%. ELISA- and CLIA-based methods performed better in terms of sensitivity (90-94%) followed by LFIA and FIA with sensitivities ranging from 80% to 86%.InterpretationELISA tests could be a safer choice at this stage of the pandemic. POC tests (LFIA), that are more attractive for large seroprevalence studies show high specificity but lower sensitivity and this should be taken into account when designing and performing seroprevalence studies.FundingNone

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Production and Evaluation of Immunoglobulin Y Anti-Brucella abortus (Vaccinal Strain B19)

Acta Scientiae Veterinariae ◽

10.22456/1679-9216.81826 ◽

2018 ◽

Vol 46 (1) ◽

pp. 8

Author(s):

Pollyanna Mafra Soares ◽

Mayara Mafra Soares ◽

Mariane Pacheco dos Santos Lourencetti ◽

Muriell Ribeiro Ganda ◽

Mariana Assunção de Souza ◽

...

Keyword(s):

Blood Serum ◽

Brucella Abortus ◽

Diagnostic Tests ◽

High Specificity ◽

Egg Yolk ◽

Control Group ◽

Immunoglobulin Y ◽

Serum Samples ◽

Specific Antibodies ◽

Group 2

Background: The immunoglobulin Y is a principal antibody current in the blood of hens, which are transferred from the maternal blood serum to the egg yolk. The extraction of IgY from the egg yolk apply animal welfare when compared to the extraction of IgG, reducing the number of animals and prevent a bleeding of hens through the extraction of the IgY from eggs, besides that IgY presenting high specificity for antigenic binding. The objective of this study was to produce specific polyclonal IgY antibodies anti-Brucella abortus by immunizing hens with B19 vaccine and evaluate their reactivity through Buffered Acidified Plate Antigen (BAPA), 2-Mercaptoethanol (2-ME) and indirect ELISA diagnostic tests.Materials, Methods & Results: Four 25-week-old White Leghorn hens were immunized, two of them comprising the control group (Group 1) with phosphate-buffered saline (PBS) with adjuvant, and the others two immunized with B19 vaccine (Brucella abortus vaccine strain B19), representing the Group 2. The immunizations occurred six times with a 15-day interval between each. Blood samples were taken biweekly (seven times); and daily, the eggs were collected for 13 weeks, the first collection of blood and eggs, performed one week before the first immunization of each group. The IgY was purified from egg yolk, using the method of dilution in acid water and precipitation with ammonium sulfate for delipidation. BAPA, 2-ME and ELISA tests performed to verify the specificity of IgY confirmed the reactivity of polyclonal antibodies specific to the antigen used both in blood serum samples and in the purified egg yolks. The hens from the control group did not present reactivity in the diagnostic tests used, which was already expected, since no antigen was used in any of their immunizations. Hens immunized with the Brucella abortus B19 vaccine produced detectable reactive antibodies in the three tests used on blood serum and IgY samples extracted from the egg yolk. In Group 2 (vaccine B19), blood serum samples started to react one week after the first inoculation, and the IgY samples extracted from the egg yolk were reagent two weeks after serum IgY appear reactivity, showing the transfer of specific antibodies to the egg yolk, was late.Discussion: Although the transfer of serum Igy to egg yolk was late when compared to others authors which found that the transovarian passage of immunoglobulin Y occurred in approximately three to six days after IgY being detected in blood serum, the results of this study showed the occurrence of the transfer of blood serum IgY anti-Brucella abortus to egg yolk of hens immunized with B19 vaccine, the same found by others researches found the same results with others antigens. Thus, it can be concluded that immunoglobulins Y produced in this study can be used as specific antibodies in diagnostic tests for the detection of the Brucella abortus antigen, in addition, this process guarantees the welfare of the animal, since it avoids bleeding and it is possible to obtain high concentrations of antibodies directly from the hen egg, which is a great advantage, because IgY can be easily isolated from the egg yolk by the precipitation technique discarding the need of invasive and painful procedures that involve bloody interventions to obtain the serum antibodies like occur in mammals for extraction of IgG.

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Ferromagnetic Resonance Biosensor for Homogeneous and Volumetric Detection of DNA

10.26434/chemrxiv.5662315.v1 ◽

2017 ◽

Author(s):

Bo Tian ◽

Peter Svedlindh ◽

Mattias Strömberg ◽

Erik Wetterskog

Keyword(s):

Magnetic Nanoparticles ◽

Ferromagnetic Resonance ◽

Limit Of Detection ◽

Point Of Care ◽

Rolling Circle Amplification ◽

Resonance Field ◽

Isothermal Amplification ◽

Detection Sensitivity ◽

Serum Samples ◽

Rolling Circle

In this work, we demonstrate for the first time, a ferromagnetic resonance (FMR) based homogeneous and volumetric biosensor for magnetic label detection. Two different isothermal amplification methods, i.e., rolling circle amplification (RCA) and loop-mediated isothermal amplification (LAMP) are adopted and combined with a standard electron paramagnetic resonance (EPR) spectrometer for FMR biosensing. For RCA-based FMR biosensor, binding of RCA products of a synthetic Vibrio cholerae target DNA sequence gives rise to the formation of aggregates of magnetic nanoparticles. Immobilization of nanoparticles within the aggregates leads to a decrease of the net anisotropy of the system and a concomitant increase of the resonance field. A limit of detection of 1 pM is obtained with an average coefficient of variation of 0.16%, which is superior to the performance of other reported RCA-based magnetic biosensors. For LAMP-based sensing, a synthetic Zika virus target oligonucleotide is amplified and detected in 20% serum samples. Immobilization of magnetic nanoparticles is induced by their co-precipitation with Mg2P2O7 (a by-product of LAMP) and provides a detection sensitivity of 100 aM. The fast measurement, high sensitivity and miniaturization potential of the proposed FMR biosensing technology makes it a promising candidate for designing future point-of-care devices.

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Magnetic Digital Microfluidics for Point-of-Care Testing: Where Are We Now?

Current Medicinal Chemistry ◽

10.2174/0929867327666200903115448 ◽

2020 ◽

Vol 27 ◽

Author(s):

Yi Zhang

Keyword(s):

System Integration ◽

Diagnostic Tests ◽

Point Of Care ◽

Digital Microfluidics ◽

Controlled Environment ◽

Point Of Care Testing ◽

Microfluidic Platforms ◽

Interface System ◽

Technical Issues ◽

Sample System

: Point-of-care (POC) testing decentralizes the diagnostic tests to the sites near the patient. Many POC tests rely microfluidic platforms for sample-to-answer analysis. Compared to other microfluidic systems, magnetic digital microfluidics demonstrate compelling advantages for POC diagnostics. In this review, we have examined the capability of magnetic digital microfluidics-based POC diagnostic platforms. More importantly, we have categorized POC settings into three classes based on “where is the point”, “who to care” and “how to test”, and evaluated the suitability of magnetic digital microfluidics in various POC settings. Furthermore, we have addressed other technical issues associated with POC testing such as controlled environment, sample-system interface, system integration and information connectivity. We hope this review would provide a guideline for the future development of magnetic digital microfluidics-based platforms for POC testing.

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A Label and Probe-Free Zika Virus Immunosensor Prussian Blue@carbon Nanotube-Based for Amperometric Detection of the NS2B Protein

Biosensors ◽

10.3390/bios11050157 ◽

2021 ◽

Vol 11 (5) ◽

pp. 157

Author(s):

Bárbara V. M. Silva ◽

Marli T. Cordeiro ◽

Marco A. B. Rodrigues ◽

Ernesto T. A. Marques ◽

Rosa F. Dutra

Keyword(s):

Carbon Nanotube ◽

Prussian Blue ◽

Zika Virus ◽

Point Of Care ◽

Amperometric Detection ◽

Cross Reactivity ◽

Structural Protein ◽

Serum Samples ◽

Polypyrrole Composite ◽

Congenital Disabilities

Zika virus (ZIKV) is a mosquito-borne infection, predominant in tropical and subtropical regions causing international concern due to the ZIKV disease having been associated with congenital disabilities, especially microcephaly and other congenital abnormalities in the fetus and newborns. Development of strategies that minimize the devastating impact by monitoring and preventing ZIKV transmission through sexual intercourse, especially in pregnant women, since no vaccine is yet available for the prevention or treatment, is critically important. ZIKV infection is generally asymptomatic and cross-reactivity with dengue virus (DENV) is a global concern. An innovative screen-printed electrode (SPE) was developed for amperometric detection of the non-structural protein (NS2B) of ZIKV by exploring the intrinsic redox catalytic activity of Prussian blue (PB), incorporated into a carbon nanotube–polypyrrole composite. Thus, this immunosensor has the advantage of electrochemical detection without adding any redox-probe solution (probe-less detection), allowing a point-of-care diagnosis. It was responsive to serum samples of only ZIKV positive patients and non-responsive to negative ZIKV patients, even if the sample was DENV positive, indicating a possible differential diagnosis between them by NS2B. All samples used here were confirmed by CDC protocols, and immunosensor responses were also checked in the supernatant of C6/36 and in Vero cell cultures infected with ZIKV.

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Long-Term Longitudinal Evaluation of Six Commercial Immunoassays for the Detection of IgM and IgG Antibodies against SARS CoV-2

Viruses ◽

10.3390/v13071244 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1244

Author(s):

Iulia Nedelcu ◽

Raluca Jipa ◽

Roxana Vasilescu ◽

Cristian Băicuș ◽

Costin-Ioan Popescu ◽

...

Keyword(s):

Clinical Performance ◽

Sample Selection ◽

Early Time ◽

Humoral Response ◽

High Specificity ◽

Data Interpretation ◽

Serum Samples ◽

Chemiluminescent Immunoassay ◽

Chemiluminescent Microparticle Immunoassay ◽

Antibody Levels

The number of serological assays for SARS-CoV-2 has skyrocketed in the past year. Concerns have been raised regarding their performance characteristics, depending on the disease severity and the time of the analysis post-symptom onset (PSO). Thus, independent validations using an unbiased sample selection are required for meaningful serology data interpretation. We aimed to assess the clinical performance of six commercially available assays, the seroconversion, and the dynamics of the humoral response to SARS-CoV-2 infection. The study included 528 serum samples from 156 patients with follow-up visits up to six months PSO and 161 serum samples from healthy people. The IgG/total antibodies positive percentage increased and remained above 95% after six months when chemiluminescent immunoassay (CLIA) IgG antiS1/S2 and electro-chemiluminescent assay (ECLIA) total antiNP were used. At early time points PSO, chemiluminescent microparticle immunoassay (CMIA) IgM antiS achieved the best sensitivity. IgM and IgG appear simultaneously in most circumstances, and when performed in parallel the sensitivity increases. The severe and the moderate clinical forms were significantly associated with higher seropositivity percentage and antibody levels. High specificity was found in all evaluated assays, but the sensitivity was variable depending on the time PSO, severity of disease, detection method and targeted antigen.

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10. Kinetics of Post-Vaccination Seroprotection to S. Pneumonia for the Immune-Compromised and Vaccine-Naïve Populations

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.055 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S27-S28

Author(s):

Jeffrey Gruenglas ◽

James Mond ◽

Micaela Scobie ◽

Cynthia Tolman ◽

Joseph Martinez

Keyword(s):

Capsular Polysaccharide ◽

The Elderly ◽

Community Acquired Pneumonia ◽

Prior History ◽

Antibody Activity ◽

Vaccine Response ◽

Serum Samples ◽

Opsonic Activity ◽

And Control

Abstract Background S. pneumonia infection presents a significant challenge, accounting for 20–38% of hospital-acquired pneumonia, and the leading cause of community-acquired pneumonia despite availability of effective vaccines. Incidence is highest in children under 2 years, the immunocompromised, and elderly. CDC has reported the emergence of antibiotic resistance in ~30% of cases, adding to risk of morbidity and mortality. Fewer than half of the elderly are vaccinated and vulnerable to infection on admission. Passive immunotherapy as an adjunct to vaccines may improve outcomes in such populations. The objective of this study was to evaluate whether seroprotective response induced with a pneumococcal conjugate vaccine could rapidly yield protective opsonic levels of antibody within anticipated duration of hospitalization. Methods Healthy donors (n=30) were immunized with Prevnar. Blood was drawn on days 0, 3, 7, 10, 14, 21, and 28. Samples were pooled and tested for presence of functional opsonic antibodies recognizing capsular polysaccharides. Clearance mechanism of S. pneumonia was based on antibody recognition to pneumococcal capsular polysaccharide and opsonic titers used as an in vitro surrogate to evaluate the efficacy of vaccine. Results There was little to no opsonic activity against most serotypes on day 0, except for low antibody activity with serotypes 1, 3, 4, and 5. Titers increased, with protective levels achieved by day 10 for most serotypes (except 14 and 18C), peaking at day 14 or after across serotypes (Figures 1 and 2). Average titers rose from log2 titer 2 on day 0 to log2 titer 8 on days 21 and 28. Titers against most serotypes reached log2 10 (titer 1024) or higher. Patients remained susceptible to nosocomial infection for at least 10 days post admission until protective titers are reached. OPK titers (log2 scale) for serum samples on day 0 (pre), day 3, 7, 10, 14, 21, 28, and control for S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V. N=2. OPK titers (log2 scale) for serum samples on day 0 (pre), day 3, 7, 10, 14, 21, 28, and control for S. pneumoniae serotypes 14, 18C, 19A, 19F, and 23F. N=2. Conclusion Patients with no prior history of vaccination (or inability to mount response) with Prevnar or pneumovax remain vulnerable to S. pneumonia infection even if vaccinated on entry, due to delayed kinetics in reaching protective titers. These patients may require prophylactic intervention of hyperimmune Ig with high opsonic titers to S. pneumonia, providing protection until vaccine response elicits protective antibodies. Disclosures All Authors: No reported disclosures

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