Cross-Reactivity Between SARS-CoV-2 Proteins and Proteins in Pneumococcal Vaccines May Protect Against Symptomatic SARS-CoV-2 Disease and Death

Protein Membrane ◽

Percent Protein ◽

Very High ◽

Local Levels

A significant inverse correlation exists between rates of pneumococcal vaccination, at both national and local levels, and symptomatic cases of SARS-CoV-2 infection and death. No correlations exist to BCG, Hib, diphtheria-tetanus-pertussis, measles-mumps-rubella, or poliovirus vaccinations. This paper explored the possibility that pneumococcal vaccines contain antigens that might be cross-reactive with SARS-CoV-2 antigens and that such cross-reactive antigens are absent from other vaccines. Comparison of the glycosylation structures of SARS-CoV-2 with the polysaccharide structures of pneumococcal vaccines yielded no obvious similarities. However, while pneumococcal vaccines are primarily composed of capsular polysaccharides, they also contain about three percent protein contaminants, including the pneumococcal surface proteins PsaA, PspA and probably PspC. These proteins have very high degrees of similarity, using very stringent criteria, with several SARS-CoV-2 proteins including the spike protein, membrane protein and replicase 1a. Equivalently similarities were found at statistically significantly lower rates, or were completely absent, among the proteins in diphtheria, tetanus, pertussis, measles, mumps, rubella, and poliovirus vaccines. Appropriate data were not available for testing Hib and BCG similarities. Notably, PspA and PspC are highly antigenic and new pneumococcal vaccines based on them are currently in human clinical trials so that their effectiveness against SARS-CoV-2 disease is easily testable.

Possible Cross-Reactivity Between SARS-CoV-2 Proteins, CRM197 and Proteins in Pneumococcal Vaccines May Protect Against Symptomatic SARS-CoV-2 Disease and Death

10.20944/preprints202007.0141.v3 ◽

2020 ◽

Author(s):

Robert Root-Bernstein

Keyword(s):

Clinical Trials ◽

Diphtheria Toxin ◽

Cross Reactivity ◽

Surface Proteins ◽

Spike Protein ◽

Pneumococcal Vaccines ◽

Protein Membrane ◽

Percent Protein ◽

Various studies indicate that vaccination, especially with pneumococcal vaccines, protects against symptomatic cases of SARS-CoV-2 infection and death. This paper explores the possibility that pneumococcal vaccines in particular, but perhaps other vaccines as well, contain antigens that might be cross-reactive with SARS-CoV-2 antigens. Comparison of the glycosylation structures of SARS-CoV-2 with the polysaccharide structures of pneumococcal vaccines yielded no obvious similarities. However, while pneumococcal vaccines are primarily composed of capsular polysaccharides, some are conjugated to CRM197, a modified diphtheria toxin, and all contain about three percent protein contaminants, including the pneumococcal surface proteins PsaA, PspA and probably PspC. All of these proteins have very high degrees of similarity, using very stringent criteria, with several SARS-CoV-2 proteins including the spike protein, membrane protein and replicase 1a. CRM197 is also present in Hib and meningitis vaccines. Equivalent similarities were found at lower rates, or were completely absent, among the proteins in diphtheria, tetanus, pertussis, measles, mumps, rubella, and poliovirus vaccines. Notably, PspA and PspC are highly antigenic and new pneumococcal vaccines based on them are currently in human clinical trials so that their effectiveness against SARS-CoV-2 disease is easily testable.

Possible Cross-Reactivity between SARS-CoV-2 Proteins, CRM197 and Proteins in Pneumococcal Vaccines May Protect Against Symptomatic SARS-CoV-2 Disease and Death

Vaccines ◽

10.3390/vaccines8040559 ◽

2020 ◽

Vol 8 (4) ◽

pp. 559 ◽

Cited By ~ 3

Author(s):

Robert Root-Bernstein

Keyword(s):

Cross Reactivity ◽

Surface Proteins ◽

Haemophilus Influenzae Type ◽

Pneumococcal Vaccines ◽

Haemophilus Influenzae Type B ◽

Type B ◽

Protein Membrane ◽

Percent Protein ◽

Various studies indicate that vaccination, especially with pneumococcal vaccines, protects against symptomatic cases of SARS-CoV-2 infection and death. This paper explores the possibility that pneumococcal vaccines in particular, but perhaps other vaccines as well, contain antigens that might be cross-reactive with SARS-CoV-2 antigens. Comparison of the glycosylation structures of SARS-CoV-2 with the polysaccharide structures of pneumococcal vaccines yielded no obvious similarities. However, while pneumococcal vaccines are primarily composed of capsular polysaccharides, some are conjugated to cross-reacting material CRM197, a modified diphtheria toxin, and all contain about three percent protein contaminants, including the pneumococcal surface proteins PsaA, PspA and probably PspC. All of these proteins have very high degrees of similarity, using very stringent criteria, with several SARS-CoV-2 proteins including the spike protein, membrane protein and replicase 1a. CRM197 is also present in Haemophilus influenzae type b (Hib) and meningitis vaccines. Equivalent similarities were found at lower rates, or were completely absent, among the proteins in diphtheria, tetanus, pertussis, measles, mumps, rubella, and poliovirus vaccines. Notably, PspA and PspC are highly antigenic and new pneumococcal vaccines based on them are currently in human clinical trials so that their effectiveness against SARS-CoV-2 disease is easily testable.

Possible Cross-Reactivity Between SARS-CoV-2 Proteins, CRM197 and Proteins in Pneumococcal Vaccines May Protect Against Symptomatic SARS-CoV-2 Disease and Death

10.20944/preprints202007.0141.v2 ◽

2020 ◽

Author(s):

Robert Root-Bernstein

Keyword(s):

Clinical Trials ◽

Diphtheria Toxin ◽

Cross Reactivity ◽

Surface Proteins ◽

Spike Protein ◽

Pneumococcal Vaccines ◽

Protein Membrane ◽

Percent Protein ◽

Various studies indicate that vaccination, especially with pneumococcal vaccines, protects against symptomatic cases of SARS-CoV-2 infection and death. This paper explores the possibility that pneumococcal vaccines in particular, but perhaps other vaccines as well, contain antigens that might be cross-reactive with SARS-CoV-2 antigens. Comparison of the glycosylation structures of SARS-CoV-2 with the polysaccharide structures of pneumococcal vaccines yielded no obvious similarities. However, while pneumococcal vaccines are primarily composed of capsular polysaccharides, some are conjugated to CRM197, a modified diphtheria toxin, and all contain about three percent protein contaminants, including the pneumococcal surface proteins PsaA, PspA and probably PspC. All of these proteins have very high degrees of similarity, using very stringent criteria, with several SARS-CoV-2 proteins including the spike protein, membrane protein and replicase 1a. CRM197 is also present in Hib and meningitis vaccines. Equivalent similarities were found at statistically significantly lower rates, or were completely absent, among the proteins in diphtheria, tetanus, pertussis, measles, mumps, rubella, and poliovirus vaccines. Notably, PspA and PspC are highly antigenic and new pneumococcal vaccines based on them are currently in human clinical trials so that their effectiveness against SARS-CoV-2 disease is easily testable.

Are the Enzyme Immunoassays for Antibodies to Pneumococcal Capsular Polysaccharides Serotype Specific?

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.7.3.468-476.2000 ◽

2000 ◽

Vol 7 (3) ◽

pp. 468-476 ◽

Cited By ~ 36

Author(s):

Anu Soininen ◽

Germie van den Dobbelsteen ◽

Lukas Oomen ◽

Helena Käyhty

Keyword(s):

Cell Wall ◽

Monoclonal Antibodies ◽

Antibody Response ◽

Enzyme Immunoassay ◽

Tetanus Toxoid ◽

Cross Reactivity ◽

Antibody Binding ◽

Pneumococcal Vaccines ◽

Reactive Antibody

ABSTRACT The specificity of antibody binding to pneumococcal capsular polysaccharides (Pnc PSs) measured by enzyme immunoassay (EIA) was studied by inhibition of antibody binding by homologous and heterologous PSs. We found extensive cross-reactivity of antibody binding to type 6B, 19F, and 23F PSs but not to type 14 PS, even after treatment with cell wall PS (CPS). The cross-reactive antibody was highly prevalent in sera of infants and adults with naturally acquired antibody, but not in sera of infants and adults immunized with pneumococcal vaccines. However, a type 11A antibody response was seen after vaccination with heterologous PSs. Monoclonal antibodies prepared against a type 6B PS-tetanus toxoid conjugate recognized also other than the specific type of PS in the EIA, implying the possible existence of a cross-reactive epitope. Remarkable differences in specificity among type 6B PS preparations from different manufacturers were found. Moreover, different lots of type 11A PS from the same manufacturer showed differences in specificity. The results suggest that some Pnc PS preparations may contain cross-reactive epitopes or impurities, other than CPS, that are common to many types of Pnc PS. The specificity of antibodies, especially in sera from nonimmunized subjects, measured by EIA can be questioned.

Cost per DALY averted in low, middle- and high-income countries: evidence from the global burden of disease study to estimate the cost-effectiveness thresholds

Cost Effectiveness and Resource Allocation ◽

10.1186/s12962-021-00260-0 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Rajabali Daroudi ◽

Ali Akbari Sari ◽

Azin Nahvijou ◽

Ahmad Faramarzi

Keyword(s):

Cost Effectiveness ◽

Inverse Correlation ◽

Gdp Per Capita ◽

Middle Income ◽

Capita Health Expenditure ◽

Per Capita ◽

Healthcare Interventions ◽

Disease Study ◽

The Cost ◽

Abstract Background Determining the cost-effectiveness thresholds for healthcare interventions has been a severe challenge for policymakers, especially in low- and middle-income countries. This study aimed to estimate the cost per disability-adjusted life-year (DALY) averted for countries with different levels of Human Development Index (HDI) and Gross Domestic Product (GDP). Methods The data about DALYs, per capita health expenditure (HE), HDI, and GDP per capita were extracted for 176 countries during the years 2000 to 2016. Then we examined the trends on these variables. Panel regression analysis was performed to explore the correlation between DALY and HE per capita. The results of the regression models were used to calculate the cost per DALY averted for each country. Results Age-standardized rate (ASR) DALY (DALY per 100,000 population) had a nonlinear inverse correlation with HE per capita and a linear inverse correlation with HDI. One percent increase in HE per capita was associated with an average of 0.28, 0.24, 0.18, and 0.27% decrease on the ASR DALY in low HDI, medium HDI, high HDI, and very high HDI countries, respectively. The estimated cost per DALY averted was $998, $6522, $23,782, and $69,499 in low HDI, medium HDI, high HDI, and very high HDI countries. On average, the cost per DALY averted was 0.34 times the GDP per capita in low HDI countries. While in medium HDI, high HDI, and very high HDI countries, it was 0.67, 1.22, and 1.46 times the GDP per capita, respectively. Conclusions This study suggests that the cost-effectiveness thresholds might be less than a GDP per capita in low and medium HDI countries and between one and two GDP per capita in high and very high HDI countries.

PYED-1 Inhibits Biofilm Formation and Disrupts the Preformed Biofilm of Staphylococcus aureus

Antibiotics ◽

10.3390/antibiotics9050240 ◽

2020 ◽

Vol 9 (5) ◽

pp. 240 ◽

Cited By ~ 1

Author(s):

Adriana Vollaro ◽

Anna Esposito ◽

Eliana Pia Esposito ◽

Raffaele Zarrilli ◽

Annalisa Guaragna ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Quorum Sensing ◽

Biofilm Formation ◽

Surface Proteins ◽

Transcriptional Analysis ◽

Dependent Manner ◽

Chronic Infections ◽

Concentration Dependent Manner ◽

Expression Of Genes

Pregnadiene-11-hydroxy-16α,17α-epoxy-3,20-dione-1 (PYED-1), a heterocyclic corticosteroid derivative of deflazacort, exhibits broad-spectrum antibacterial activity against Gram-negative and Gram-positive bacteria. Here, we investigated the effect of PYED-1 on the biofilms of Staphylococcus aureus, an etiological agent of biofilm-based chronic infections such as osteomyelitis, indwelling medical device infections, periodontitis, chronic wound infections, and endocarditis. PYED-1 caused a strong reduction in biofilm formation in a concentration dependent manner. Furthermore, it was also able to completely remove the preformed biofilm. Transcriptional analysis performed on the established biofilm revealed that PYED-1 downregulates the expression of genes related to quorum sensing (agrA, RNAIII, hld, psm, and sarA), surface proteins (clfB and fnbB), secreted toxins (hla, hlb, and lukD), and capsular polysaccharides (capC). The expression of genes that encode two main global regulators, sigB and saeR, was also significantly inhibited after treatment with PYED-1. In conclusion, PYED-1 not only effectively inhibited biofilm formation, but also eradicated preformed biofilms of S. aureus, modulating the expression of genes related to quorum sensing, surface and secreted proteins, and capsular polysaccharides. These results indicated that PYED-1 may have great potential as an effective antibiofilm agent to prevent S. aureus biofilm-associated infections.

Serogroups of the beer spoilage bacterium Megasphaera cerevisiae correlate with the molecular weight of the major EDTA-extractable surface protein

Canadian Journal of Microbiology ◽

10.1139/w99-123 ◽

2000 ◽

Vol 46 (2) ◽

pp. 95-100 ◽

Cited By ~ 5

Author(s):

Barry Ziola ◽

Lori Gee ◽

Nancy N Berg ◽

Sun Y Lee

Keyword(s):

Ethylenediaminetetraacetic Acid ◽

Polyacrylamide Gel Electrophoresis ◽

Sodium Dodecyl ◽

Surface Protein ◽

Cross Reactivity ◽

Surface Reactivity ◽

Surface Proteins ◽

Bacterial Surface ◽

Spoilage Bacteria ◽

Beer Spoilage

Megasphaera cerevisiae is a Gram-negative obligate anaerobe that causes turbidity and off-flavour and aroma in beer. Seven isolates of M. cerevisiae were obtained worldwide, and their extractable surface antigens were focused upon to determine if there is more than one serogroup of this bacterium. Sodium dodecyl sulphate polyacrylamide gel electrophoresis of ethylenediaminetetraacetic acid (EDTA) bacterial extracts revealed a predominant protein with apparent molecular weights of 46 000, 45 000, and 43 000 for three, two, and two isolates, respectively. When mouse antiserum generated against any of the EDTA extracts was reacted with denatured bacterial proteins in immunoblots, all bacterial isolates exhibited extensive cross-reactivity involving three antigens, one being the major EDTA-extractable protein. In contrast, when the sera were tested for surface reactivity with intact bacteria, three cross-reactivity groups were observed, with the groups individually comprised of bacteria having the same size major EDTA-extractable surface protein. When BALB/c mice immunized with a bacterium from each of the three serogroups were used for monoclonal antibody (Mab) hybridoma production, bacterial surface-reactive Mabs were obtained whose reactivities parallel the three polyclonal antibody-defined serogroups. Through combining these surface-reactive Mabs, it will be possible to rapidly detect and identify beer contamination by M. cerevisiae belonging to any serogroup. Key words: beer spoilage bacteria, Megasphaera cerevisiae, monoclonal antibodies, surface proteins, serogroups.

Cross-Reactivity between Immune Responses to Helicobacter bilis and Helicobacter pylori in a Population in Thailand at High Risk of Developing Cholangiocarcinoma

Clinical and Vaccine Immunology ◽

10.1128/cvi.00132-08 ◽

2008 ◽

Vol 15 (9) ◽

pp. 1363-1368 ◽

Cited By ~ 15

Author(s):

Paola Pisani ◽

Mark T. Whary ◽

Ingrid Nilsson ◽

Supannee Sriamporn ◽

Torkel Wadström ◽

...

Keyword(s):

High Risk ◽

Immune Responses ◽

Cross Reactivity ◽

Surface Proteins ◽

Massachusetts Institute Of Technology ◽

Whole Cell ◽

Serologic Tests ◽

Helicobacter Bilis ◽

Institute Of Technology ◽

H Pylori

ABSTRACT Helicobacter bilis DNA has been detected in human tissue and is a candidate for etiologic investigations on the causes of hepatic and biliary tract diseases, but reliable serologic tests need to be developed in order to pursue such investigations. The scope of this study was to assess the specificity of two assays for H. bilis immune response allowing for H. pylori, and their cross-reactivity in a population in Thailand at high risk for cholangiocarcinoma. Plasma samples from 92 Thai volunteers were independently tested in two laboratories (Massachusetts Institute of Technology [MIT] and Lund). MIT performed three analyses of H. pylori and H. bilis based either on (i) outer membrane protein (OMP) with no preabsorption or on antigens derived from whole-cell sonicate before (ii) or after (iii) preabsorption with H. pylori sonicate protein. Lund used cell surface proteins from H. pylori and H. bilis as antigens. Testing for H. bilis was preabsorbed with a whole-cell lysate of H. pylori. More than 80% of the samples were positive for H. pylori in both laboratories. As tested by MIT, 58.7% (95% confidence interval, 47.9 to 68.9%) were positive for H. bilis by OMP and 44.5% (34.1 to 55.3%) were positive for H. bilis sonicate protein, but only 15.2% (8.6 to 24.2%) remained positive after preabsorption with H. pylori sonicate protein. Lund found 34.5% of the samples positive for H. bilis (22.0 to 41.0%), which was statistically compatible with all three MIT results. Serologic responses to OMPs of the two bacteria coincided in 66 and 45% of the samples in the MIT and Lund assays, respectively. We found high cross-reactivity between the immune responses to H. pylori and H. bilis antigens. More-specific H. bilis antigens need to be isolated to develop serologic tests suitable for epidemiological studies.

Comparative Evaluation of Enzyme-Linked Immunosorbent Assays Based on Crude and Recombinant Leishmanial Antigens for Serodiagnosis of Symptomatic and Asymptomatic Leishmania infantum Visceral Infections in Dogs

Clinical and Vaccine Immunology ◽

10.1128/cvi.00420-06 ◽

2007 ◽

Vol 14 (5) ◽

pp. 544-548 ◽

Cited By ~ 81

Author(s):

Renato Porrozzi ◽

Marcos V. Santos da Costa ◽

Antonio Teva ◽

Aloísio Falqueto ◽

Adelson L. Ferreira ◽

...

Keyword(s):

Rural Areas ◽

Leishmania Infantum ◽

Leishmania Donovani ◽

Cross Reactivity ◽

Enzyme Linked Immunosorbent Assay ◽

Leishmania Braziliensis ◽

Soluble Antigen ◽

Negative Controls ◽

Epitope Selection ◽

ABSTRACT The diagnosis of visceral leishmaniasis remains difficult in rural areas where the disease is endemic, and serologic methods still need assessment, as they are not very sensitive for the detection of asymptomatic infectious dogs. Here we present data on the development of enzyme-linked immunosorbent assay (ELISA)-based methods for the detection of antibodies against recombinant leishmanial antigens (namely, the recombinant K26 [rK26] and rK39 antigens from Leishmania infantum and the rA2 protein from Leishmania donovani) in comparison to ELISAs employing crude soluble antigen (CSA). The assays utilized sera from known negative controls (n = 25) and clinically asymptomatic (n = 50) and symptomatic (n = 50) dogs with confirmed L. infantum infections. Additional studies were also done using sera from animals harboring other infections (n = 14) for the evaluation of cross-reactivity. Our study indicated that rK26 and rK39 used in ELISAs provided very high sensitivities for the detection of symptomatic dogs (94% and 100%, respectively), followed by CSA (88%) and rA2 (70%). Conversely, rA2 was more sensitive for asymptomatic dogs (88%) than rK39 and rK26 (both 66%) and CSA (30%). Some cross-reactivity in sera from dogs with other infections (Leishmania braziliensis and Leptospira interrogans) was identified, but the rA2 protein provided the greatest specificity (98%). Data further indicate that all three recombinant proteins must be used in parallel to detect essentially all infected dogs. Efforts should be made to develop a cheap and reliable serologic test based on epitope selection from these diagnostic markers for the sensitive detection of L. infantum-infected dogs.

Placental alkaline phosphatase as a tumor marker for primary intracranial germinoma

Journal of Neurosurgery ◽

10.3171/jns.1988.68.5.0710 ◽

1988 ◽

Vol 68 (5) ◽

pp. 710-720 ◽

Cited By ~ 45

Author(s):

Jun Shinoda ◽

Hiromu Yamada ◽

Noboru Sakai ◽

Takashi Ando ◽

Toshifumi Hirata ◽

...

Keyword(s):

Alkaline Phosphatase ◽

Tumor Marker ◽

Cross Reactivity ◽

Cyst Fluid ◽

Enzyme Linked Immunosorbent Assay ◽

Placental Alkaline Phosphatase ◽

Intestinal Alkaline Phosphatase ◽

Content Type ◽

Intracranial Germinoma ◽

✓ A sensitive enzyme-linked immunosorbent assay (ELISA) was used in a retrospective study of placental alkaline phosphatase (PLAP) levels in serum, cerebrospinal fluid (CSF), and intratumoral cyst fluid in primary intracranial germinoma. The ELISA showed no cross-reactivity with intestinal alkaline phosphatase except in very high concentrations, after samples had been heat-treated. Three patients with germinoma were studied for serum PLAP levels and in all the levels were elevated (3.78, 0.52, and 2.11 IU/liter). Two of the germinoma patients were studied for PLAP levels in the CSF, and both had elevated levels (0.83 and 9.83 IU/liter). The intratumoral cyst fluid in one case of germinoma was tested for PLAP and the level was found to be very high (603 IU/liter). These PLAP levels decreased concomitantly with the reduction in tumor size during irradiation. Serum PLAP levels were measured in 40 control adult male individuals and in the CSF of 20 nonpregnant patients with subarachnoid hemorrhage. The upper normal limits were 0.20 and 0.11 IU/liter in the serum and the CSF, respectively. All PLAP levels measured in the serum of patients with various brain tumors were 0.18 IU/liter or less. This study strongly suggests that PLAP is a clinically useful tumor marker for primary intracranial germinoma.