Development of combination vaccine conferring optimal protection against six pore-forming toxins of Staphylococcus aureus

In Gram-positive pathogen Staphylococcus aureus , pore-forming toxins (PFTs) such as leukocidins and hemolysins play prominent roles in staphylococcal pathogenesis by killing host immune cells and red blood cells (RBCs). However, it remains unknown which combination of toxin antigens would induce the broadest protective immune response against those toxins. In this study, by targeting six major staphylococcal PFTs (i.e., HlgAB, HlgCB, LukAB, LukED, LukSF-PV, and Hla), we generated ten recombinant toxins or toxin-subunits, three toxoids, and their rabbit antibodies. Using the cytolytic assay for RBCs and polymorphonuclear cells (PMNs), we determined the best combination of toxin antibodies conferring the broadest protection against those staphylococcal PFTs. Although anti-HlgA IgG (HlgA-IgG) showed low cross-reactivity to other toxin components, it was essential to protect rabbit and human RBCs and human PMNs. For the protection of rabbit RBCs, Hla H35L toxoid-IgG was also required, whereas, for human PMNs, LukS-IgG and LukA E323A B-IgG were essential too. When the toxin/toxoid antigens HlgA, LukS-PV, Hla H35L , and LukA E323A B were used to immunize rabbits, they increased rabbit survival; however, they did not block staphylococcal abscess formation in kidneys. Based on these results, we proposed that the combination of HlgA, LukS, Hla H35L , and LukA E323A B is the optimal vaccine component to protect human RBCs and PMNs from staphylococcal PFTs. We also concluded that a successful S. aureus vaccine requires not only those toxin antigens but also other antigens that can induce immune response blocking staphylococcal colonization.

Allergy to Polyethilenglicole of Anti-SARS CoV2 Vaccine Recipient: A Case Report of Young Adult Recipient and the Management of Future Exposure to SARS-CoV2

The main contraindication to the anti-SARS CoV2 vaccine is an anaphylactic reaction to a vaccine component. The need to vaccinate allergic people who are at higher risk can be of public health interest and this report shows a case of an allergic reaction to PEG of a HCW who had received the first dose of anti-SARS CoV2 vaccine. For 5 h after the administration of the vaccine, she had the appearance of erythematous spots on the face and neck, and a feeling of a slurred mouth and hoarseness. In order to treat the event, she was administered 8 mg intravenous dexamethasone, 1 vial intravenous chlorphenamine maleate, 250 mL intravenous 0.9% NaCl, and conventional oxygen therapy (2 L/min) with complete resolution of the suspected adverse drug reaction. According to the contraindication to the cutaneous test for this patient, BAT was used for further investigations. The patient who suffered the adverse reaction to the COVID-19 vaccine and other five allergic patients who did not report any adverse reaction after the vaccination were tested. There was a significant activation of the vaccine-reactive patient’s basophils with 14.79 CD203chigh% at the concentration of 0.2 mg/mL, while other patients were negative. People who have a confirmed reaction to a vaccine component should undergo further investigation to discover other possible cross-reactions and select the right vaccine to immunize them.

Differential Influence of Age on the Relationship between Genetic Mismatch and A(H1N1)pdm09 Vaccine Effectiveness

Assessment of influenza vaccine effectiveness (VE) and identification of relevant influencing factors are the current priorities for optimizing vaccines to reduce the impacts of influenza. To date, how the difference between epidemic strains and vaccine strains at genetic scale affects age-specific vaccine performance remains ambiguous. This study investigated the association between genetic mismatch on hemagglutinin and neuraminidase genes and A(H1N1)pdm09 VE in different age groups with a novel computational approach. We found significant linear relationships between VE and genetic mismatch in children, young adults, and middle-aged adults. In the children’s group, each 3-key amino acid mutation was associated with an average of 10% decrease in vaccine effectiveness in a given epidemic season, and genetic mismatch exerted no influence on VE for the elderly group. We demonstrated that present vaccines were most effective for children, while protection for the elderly was reduced and indifferent to vaccine component updates. Modeling such relationships is practical to inform timely evaluation of VE in different groups of populations during mass vaccination and may inform age-specific vaccination regimens.

A tetravalent live attenuated dengue virus vaccine stimulates balanced immunity to multiple serotypes in humans

The four-dengue virus (DENV) serotypes infect several hundred million people annually. For the greatest safety and efficacy, tetravalent DENV vaccines are designed to stimulate balanced protective immunity to all four serotypes. However, this has been difficult to achieve. Clinical trials with a leading vaccine demonstrated that unbalanced replication and immunodominance of one vaccine component over others can lead to low efficacy and vaccine enhanced severe disease. The Laboratory of Infectious Diseases at the National Institutes of Health has developed a live attenuated tetravalent DENV vaccine (TV003), which is currently being tested in phase 3 clinical trials. Here we report, our study to determine if TV003 stimulate balanced and serotype-specific (TS) neutralizing antibody (nAb) responses to each serotype. Serum samples from twenty-one dengue-naive individuals participated under study protocol CIR287 (ClinicalTrials.gov NCT02021968) are analyzed 6 months after vaccination. Most subjects (76%) develop TS nAbs to 3 or 4 DENV serotypes, indicating immunity is induced by each vaccine component. Vaccine-induced TS nAbs map to epitopes known to be targets of nAbs in people infected with wild type DENVs. Following challenge with a partially attenuated strain of DENV2, all 21 subjects are protected from the efficacy endpoints. However, some vaccinated individuals develop post challenge nAb boost, while others mount post-challenge antibody responses that are consistent with sterilizing immunity. TV003 vaccine induced DENV2 TS nAbs are associated with sterilizing immunity. Our results indicate that nAbs to TS epitopes on each serotype may be a better correlate than total levels of nAbs currently used for guiding DENV vaccine development.

Conserved Structural Features of Core Oligosaccharides among the Lipopolysaccharides of Respiratory Pathogens from the Genus Bordetella Analyzed Exclusively by NMR Spectroscopy

Bacterial pathogens expose on the cell surface a variety of complex carbohydrate molecules. Gram-negative bacteria produce lipopolysaccharides, which are the main components of the outer membrane of bacterial envelopes and play a major role in host–pathogen interactions. B. pertussis, B. parapertussis, B. bronchiseptica, and B. holmesii, are mammalian respiratory pathogens, having substantial economic impact on human health and agriculture. B. pertussis is responsible for whooping cough (pertussis) and B. holmesii is the second pertussis etiological factor, but the current anti-pertussis vaccines do not provide cross-protection. The structural data on any given hypothetical carbohydrate antigen is a prerequisite for further analysis of structure-related activities and their interaction with hosts. 1H NMR spectra constitute fingerprints of the analyzed glycans and provide unique identity information. The concept of structure-reporter groups has now been augmented by 1H,13C-correlation spectra of the Bordetella oligosaccharides. The comparative analysis of Bordetellae oligosaccharides (OS) revealed that the hexasaccharide, comprising the α-GlcpN, α-GlcpA, 4,6-disubstituted-β-Glcp, 2,7-disubstituted-l-α-d-Hepp, 3,4-disubstituted-l-α-d-Hepp, and Kdo, constitute the least variable OS segment. This minimal common element in the structure of lipopolysaccharides of Bordetellae could be used to devise a universal cross-protective vaccine component against infections with various bacteria from the genus Bordetella.

131 Producer adoption of preconditioning strategies in the Oklahoma Quality Beef Network

The Oklahoma Quality Beef Network (OQBN) Vac-45 program was designed to provide health management certification and value-added marketing for cow-calf producers since 2001. The objective of this abstract is to examine trends in health management systems by OQBN participants. Participants chose from one of three options for administering vaccinations: Option 1) branding and weaning, Option 2) 2–6 weeks before weaning and weaning, Option 3) weaning and 14–28 d post weaning. From 2014–2018, 596 participants enrolled 30,452 calves. Preferred vaccine options were: Option 1) 210 participants (35%) and 12,015 calves (37%), Option 2) 96 participants (16%) and 3,016 calves (10%), Option 3) 290 participants (49%) and 15,421 calves (51%). Producer choice of a viral vaccine component included 251 (42%) participants using killed vaccine at least once. A five-yr average of cattle marketed with at least one modified-live vaccine (MLV) exposure was 73% of calves (22,138) and 27% (8,314) were treated with only killed vaccines. In Option 1, 57 (10% of the total) participants used killed vaccines at both times, 33 (6%) used a killed vaccine followed by a MLV at weaning, 120 (20%) used MLV at both times. Option 2, 55 (9%) participants used killed vaccines at both times, 4 (1%) participants used a killed vaccine follow by a MLV at weaning; 37 (6%) used a MLV at both times. Option 3, 114 (19%) participants used killed vaccines at both times, 2 (< 1%) participant used a killed vaccine followed by a MLV, 1 participant used MLV followed by killed vaccine, 173 (29%) participants used MLV at both times. Cattle marketed with killed vaccines have seen an increase in use; 2014 (27%), 2015 (17%), 2016 (27%), 2017 (31%), 2018 (39%). These data show the preferred method of MLV vaccination utilized is a weaning and post-weaning system with an increased use of killed vaccines, which may be due to producer concerns regarding exposure of brood cows to MLV.