scholarly journals Differences in Pneumococcal and Haemophilus influenzae Natural Antibody Development in Papua New Guinean Children in the First Year of Life

2021 ◽  
Vol 12 ◽  
Author(s):  
Kelly M. Martinovich ◽  
Tasmina Rahman ◽  
Camilla de Gier ◽  
Elke J. Seppanen ◽  
Tilda Orami ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Vaccine Development ◽  
Geometric Mean ◽  
Clinical Trial Registration ◽  
Middle Income ◽  
Global Priority ◽  
Antibody Titres ◽  
Specific Igg ◽  
Species Specific ◽  
Papua New Guinean

BackgroundDevelopment of vaccines to prevent disease and death from Streptococcus pneumoniae, and nontypeable Haemophilus influenzae (NTHi), the main pathogens that cause otitis media, pneumonia, meningitis and sepsis, are a global priority. Children living in low and lower-middle income settings are at the highest risk of contracting and dying from these diseases. Improved vaccines with broader coverage are required. Data on the natural development of antibodies to putative vaccine antigens, especially in high-risk settings, can inform the rational selection of the best antigens for vaccine development.MethodsSerum IgG titres to four pneumococcal proteins (PspA1, PspA2, CbpA, and Ply) and five NTHi antigens (P4, P6, OMP26, rsPilA and ChimV4) were measured in sera collected from 101 Papua New Guinean children at 1, 4, 9, 10, 23 and 24 months of age using multiplexed bead-based immunoassays. Carriage density of S. pneumoniae and H. influenzae were assessed by quantitative PCR on genomic DNA extracted from nasopharyngeal swabs using species-specific primers and probes. All data were log-transformed for analysis using Student’s unpaired t-tests with geometric mean titre (GMT) or density (GMD) calculated with 95% confidence intervals (CI).ResultsSerum -pneumococcal protein-specific IgG titres followed a “U” shaped pattern, with a decrease in presumably maternally-derived IgG titres between 1 and 4 months of age and returning to similar levels as those measured at 1 month of age by 24 months of age. In contrast, NTHi protein-specific IgG titres steadily increased with age. There was no correlation between antibody titres and carriage density for either pathogen.ConclusionThis longitudinal study indicates that the waning of maternally- derived antibodies that is usually observed in infants, after infants does not occur for NTHi antigens in Papua New Guinean infants. Whether NTHi antigen IgG can be transferred maternally remains to be determined. Vaccines that are designed to specifically increase the presence of protective NTHi antibodies in the first few months of life may be most effective in reducing NTHi disease.Clinical Trial Registrationhttps://clinicaltrials.gov/, identifier NCT01619462.

scholarly journals Safety, immunogenicity and risk–benefit analysis of rVSV-ΔG-ZEBOV-GP (V920) Ebola vaccine in Phase I–III clinical trials across regions

2020 ◽  
Vol 15 (2) ◽  
pp. 85-106 ◽  
Author(s):  
Bache Emmanuel Bache ◽  
Martin P Grobusch ◽  
Selidji Todagbe Agnandji
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Geometric Mean ◽  
Middle Income ◽  
Infected People ◽  
Middle Income Countries ◽  
Efficacy Trials ◽  
Low Middle Income Countries ◽  
Antibody Titres ◽  
Women And Hiv

To evaluate the risk–benefits balance of the rVSV-ΔG-ZEBOV-GP vaccine. We performed a systematic review to summarize data on safety, immunogenicity and efficacy. About 17,600 adults and 234 children received 11 different doses of the V920 vaccine ranging from 3000 to 100 million and 20 million plaque-forming units, respectively, during Phase I–III clinical trials. Cases of severe but transient arthritis were reported in about six and 0.08% of vaccinees in high-income countries (HICs) and low–middle-income countries (LMICs), respectively. The 20 million plaque-forming units dose yielded GP-specific antibody titres which peaked at day 28 with a pooled geometric mean titres of 2557.7 (95% CI: 1665.5–3934.2) versus 1156.9 (95% CI: 832.5–1649.2) but with similar seroconversion rates at 96% (95% CI: 87–100) versus 100% (95% CI: 90–100) for HICs and LMICs, respectively. Data from stringent Phase I–II clinical trials in LMICs and HICs and from the ring efficacy trials yielded a good risk–benefit balance of the V920 vaccine in adults, but also in children and pregnant and lactating women and HIV-infected people.

scholarly journals Shigella-specific antibodies in the first year of life among Zambian infants: A longitudinal cohort study

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0252222
Author(s):  
Caroline C. Chisenga ◽  
Samuel Bosomprah ◽  
Michelo Simuyandi ◽  
Katayi Mwila-Kazimbaya ◽  
Obvious N. Chilyabanyama ◽  
...  
Keyword(s):  
Geometric Mean ◽  
Significant Rise ◽  
Enzyme Linked Immunosorbent Assay ◽  
First Year ◽  
Middle Income ◽  
Specific Antibodies ◽  
Middle Income Countries ◽  
Specific Igg ◽  
First Year Of Life ◽  
Related Mortality

Introduction Shigellosis, is a leading cause of moderate-to-severe diarrhoea and related mortality in young children in low and middle income countries (LMICs). Knowledge on naturally acquired immunity can support the development of Shigella candidate vaccines mostly needed in LMICs. We aimed to quantify Shigella-specific antibodies of maternal origin and those naturally acquired in Zambian infants. Methods Plasma samples collected from infants at age 6, 14 and 52-weeks were tested for Shigella (S. sonnei and S. flexneri 2a) lipopolysaccharide (LPS) antigen specific immunoglobulin G (IgG) and A (IgA) by enzyme-linked immunosorbent assay. Results At 6 weeks infant age, the IgG geometric mean titres (GMT) against S. sonnei (N = 159) and S. flexneri 2a (N = 135) LPS were 311 (95% CI 259–372) and 446 (95% CI 343–580) respectively. By 14 weeks, a decline in IgG GMT was observed for both S. sonnei to 104 (95% CI 88–124), and S. flexneri 2a to 183 (95% CI 147–230). Both S. sonnei and S. flexneri 2a specific IgG GMT continued to decrease by 52 weeks infant age when compared to 6 weeks. In 27% and 8% of infants a significant rise in titre (4 fold and greater) against S. flexneri 2a and S. sonnei LPS, respectively, was detected between the ages of 14 and 52 weeks. IgA levels against both species LPS were very low at 6 and 14 weeks and raised significantly against S. flexneri 2a and S. sonnei LPS in 29% and 10% of the infants, respectively. Conclusion In our setting, transplacental IgG anti-Shigella LPS is present at high levels in early infancy, and begins to decrease by age 14 weeks. Our results are consistent with early exposure to Shigella and indicate naturally acquired IgG and IgA antibodies to S. flexneri 2a and S. sonnei LPS in part of infants between 14 and 52 weeks of age. These results suggest that a potential timing of vaccination would be after 14 and before 52 weeks of age to ensure early infant protection against shigellosis.

scholarly journals Sequence analysis of Plasmodium vivax Duffy binding proteins reveals the presence of unique haplotypes and diversifying selection in Ethiopian isolates

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Lemu Golassa ◽  
Alebachew Messele ◽  
Eniyou Cheryll Oriero ◽  
Alfred Amambua-Ngwa
Keyword(s):  
Vaccine Development ◽  
Haplotype Diversity ◽  
Sri Lankan ◽  
Duffy Binding Protein ◽  
Synonymous Mutations ◽  
South Korean ◽  
Blood Stage Infection ◽  
Vaccine Approach ◽  
Papua New Guinean ◽  
Reference Haplotype

Abstract Background Red blood cell invasion by the Plasmodium vivax merozoite requires interaction between the Duffy antigen receptor for chemokines (DARC) and the P. vivax Duffy-binding protein II (PvDBPII). Given that the disruption of this interaction prevents P. vivax blood-stage infection, a PvDBP-based vaccine development has been well recognized. However, the polymorphic nature of PvDBPII prevents a strain transcending immune response and complicates attempts to design a vaccine. Methods Twenty-three P. vivax clinical isolates collected from three areas of Ethiopia were sequenced at the pvdbpII locus. A total of 392 global pvdbpII sequences from seven P. vivax endemic countries were also retrieved from the NCBI archive for comparative analysis of genetic diversity, departure from neutrality, linkage disequilibrium, genetic differentiation, PvDBP polymorphisms, recombination and population structure of the parasite population. To establish a haplotype relationship a network was constructed using the median joining algorithm. Results A total of 110 variable sites were found, of which 44 were parsimony informative. For Ethiopian isolates there were 12 variable sites of which 10 were parsimony informative. These parsimony informative variants resulted in 10 nonsynonymous mutations. The overall haplotype diversity for global isolates was 0.9596; however, the haplotype diversity was 0.874 for Ethiopia. Fst values for genetic revealed Ethiopian isolates were closest to Indian isolates as well as to Sri Lankan and Sudanese isolates but further away from Mexican, Papua New Guinean and South Korean isolates. There was a total of 136 haplotypes from the 415 global isolates included for this study. Haplotype prevalence ranged from 36.76% to 0.7%, from this 74.2% were represented by single parasite isolates. None of the Ethiopian isolates grouped with the Sal I reference haplotype. From the total observed nonsynonymous mutations 13 mapped to experimentally verified epitope sequences. Including 10 non-synonymous mutations from Ethiopia. However, all the polymorphic regions in Ethiopian isolates were located away from DARC, responsible for junction formation. Conclusion The results of this study are concurrent with the multivalent vaccine approach to design an effective treatment. However, the presence of novel haplotypes in Ethiopian isolates that were not shared by other global sequences warrant further investigation.

scholarly journals SARS-CoV-2 specific antibody and neutralization assays reveal the wide range of the humoral immune response to virus

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mikail Dogan ◽  
Lina Kozhaya ◽  
Lindsey Placek ◽  
Courtney Gunter ◽  
Mesut Yigit ◽  
...  
Keyword(s):  
Specific Antibody ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
High Specificity ◽  
Spike Protein ◽  
Humoral Immune ◽  
Specificity And Sensitivity ◽  
Wide Range ◽  
Specific Igg ◽  
Negative Controls

AbstractDevelopment of antibody protection during SARS-CoV-2 infection is a pressing question for public health and for vaccine development. We developed highly sensitive SARS-CoV-2-specific antibody and neutralization assays. SARS-CoV-2 Spike protein or Nucleocapsid protein specific IgG antibodies at titers more than 1:100,000 were detectable in all PCR+ subjects (n = 115) and were absent in the negative controls. Other isotype antibodies (IgA, IgG1-4) were also detected. SARS-CoV-2 neutralization was determined in COVID-19 and convalescent plasma at up to 10,000-fold dilution, using Spike protein pseudotyped lentiviruses, which were also blocked by neutralizing antibodies (NAbs). Hospitalized patients had up to 3000-fold higher antibody and neutralization titers compared to outpatients or convalescent plasma donors. Interestingly, some COVID-19 patients also possessed NAbs against SARS-CoV Spike protein pseudovirus. Together these results demonstrate the high specificity and sensitivity of our assays, which may impact understanding the quality or duration of the antibody response during COVID-19 and in determining the effectiveness of potential vaccines.

scholarly journals Effects of Size and Surface Properties of Nanodiamonds on the Immunogenicity of Plant-Based H5 Protein of A/H5N1 Virus in Mice

Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1597
Author(s):  
Thuong Thi Ho ◽  
Van Thi Pham ◽  
Tra Thi Nguyen ◽  
Vy Thai Trinh ◽  
Tram Vi ◽  
...  
Keyword(s):  
High Pressure ◽  
Neutralizing Antibodies ◽  
H5n1 Virus ◽  
Vaccine Development ◽  
Particle Characterization ◽  
Innovative Strategy ◽  
Specific Igg ◽  
Positively Charged

Nanodiamond (ND) has recently emerged as a potential nanomaterial for nanovaccine development. Here, a plant-based haemagglutinin protein (H5.c2) of A/H5N1 virus was conjugated with detonation NDs (DND) of 3.7 nm in diameter (ND4), and high-pressure and high-temperature (HPHT) oxidative NDs of ~40–70 nm (ND40) and ~100–250 nm (ND100) in diameter. Our results revealed that the surface charge, but not the size of NDs, is crucial to the protein conjugation, as well as the in vitro and in vivo behaviors of H5.c2:ND conjugates. Positively charged ND4 does not effectively form stable conjugates with H5.c2, and has no impact on the immunogenicity of the protein both in vitro and in vivo. In contrast, the negatively oxidized NDs (ND40 and ND100) are excellent protein antigen carriers. When compared to free H5.c2, H5.c2:ND40, and H5.c2:ND100 conjugates are highly immunogenic with hemagglutination titers that are both 16 times higher than that of the free H5.c2 protein. Notably, H5.c2:ND40 and H5.c2:ND100 conjugates induce over 3-folds stronger production of both H5.c2-specific-IgG and neutralizing antibodies against A/H5N1 than free H5.c2 in mice. These findings support the innovative strategy of using negatively oxidized ND particles as novel antigen carriers for vaccine development, while also highlighting the importance of particle characterization before use.

scholarly journals Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Adam K. Wheatley ◽  
Jennifer A. Juno ◽  
Jing J. Wang ◽  
Kevin J. Selva ◽  
Arnold Reynaldi ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Vaccine Development ◽  
Natural Infection ◽  
Population Level ◽  
Cell Dynamics ◽  
Follicular Helper ◽  
Cell Immunity ◽  
Specific Igg ◽  
Over Time

AbstractThe durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with individual serum clonotypes, decay over the first 4 months post-infection. A similar decline in Spike-specific CD4+ and circulating T follicular helper frequencies occurs. By contrast, S-specific IgG+ memory B cells consistently accumulate over time, eventually comprising a substantial fraction of circulating the memory B cell pool. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent participants to 74 days, although there is probably additive protection from B cell and T cell immunity. This study indicates that SARS-CoV-2 immunity after infection might be transiently protective at a population level. Therefore, SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long-term protection.

scholarly journals Antigenic diversity and seroprevalences of Torque teno viruses in children and adults by ORF2-based immunoassays

2013 ◽  
Vol 94 (2) ◽  
pp. 409-417 ◽  
Author(s):  
Tingting Chen ◽  
Elina Väisänen ◽  
Petri S. Mattila ◽  
Klaus Hedman ◽  
Maria Söderlund-Venermo
Keyword(s):  
Serum Samples ◽  
Phylogenetic Groups ◽  
Single Strain ◽  
New Approach ◽  
Antiviral Antibody ◽  
Specific Igg ◽  
Species Specific ◽  
Multiple Strains ◽  
Antigenic Relationships

Torque teno viruses (TTVs) circulate widely among humans, causing persistent viraemia in healthy individuals. Numerous TTV isolates with high genetic variability have been identified and segregated into 29 species of five major phylogenetic groups. To date, the diversity of TTV sequences, challenges in protein expression and the subsequent lack of serological assays have hampered TTV seroprevalence studies. Moreover, the antigenic relationships of different TTVs and their specific seroprevalences in humans remain unknown. For five TTV strains – belonging to different species of four genogroups – we developed, using recombinant glutathione S-transferase (GST)-fused TTV ORF2 proteins, glutathione–GST capture enzyme immunoassays (EIAs) detecting antibodies towards conformational epitopes. We then analysed serum samples from 178 healthy adults and 108 children; IgG reactivities were observed either towards a single strain or towards multiple strains, which pointed to antigenic distinction of TTV species. The overall seroprevalence for the five TTVs peaked at 43 % (18 of 42) in children 2–4 years of age, subsequently declined, and again reached 42 % (74 of 178) among adults. TTV6 species-specific IgG predominated in children, whereas that for TTV13 predominated in adults. During a 3 year follow-up of the same children, both species-specific seroconversions and seroreversions occurred. This is the first EIA-based study of different TTVs, providing a new approach for seroepidemiology and diagnosis of TTV infections. Our data suggest that different TTVs in humans may differ in antiviral antibody profiles, infection patterns and epidemiology.

Immunogenicity of Haemophilus influenzae Type b Polysaccharide-Neisseria meningitidis Outer Membrane Protein Conjugate Vaccine in 2- to 6-Month-Old Infants

PEDIATRICS ◽  
1987 ◽  
Vol 80 (2) ◽  
pp. 283-287
Author(s):  
Allen A. Lenoir ◽  
Paul D. Granoff ◽  
Dan M. Granoff
Keyword(s):  
Membrane Protein ◽  
Haemophilus Influenzae ◽  
Neisseria Meningitidis ◽  
Outer Membrane Protein ◽  
Geometric Mean ◽  
Serum Antibody ◽  
Haemophilus Influenzae Type ◽  
Antibody Concentration ◽  
Haemophilus Influenzae Type B ◽  
Type B

Fifty infants, 2 to 6 months of age, were vaccinated with Haemophilus influenzae type b capsular polysaccharide covalently linked to an outer membrane protein from Neisseria meningitidis group B. Subjects were given two injections and were randomly assigned to receive the injections separated by 1 or 2 months. Each dose contained 15 µg of polysaccharide and 51 µg of protein, or approximately twice the amount of polysaccharide as used in our previous trial (Lancet 1986;2:299). Fevers of 38.0° to 38.8°C developed in three infants (6%) within 24 hours after vaccination, but there were no other notable reactions. Following one injection, the geometric mean antibody concentration increased from 0.13 µg/mL in preimmune serum to 1.50 µg/mL in serum obtained 1 to 2 months later (P < .001). After a second injection, there was a further increase in serum antibody (geometric mean = 3.11 µg/mL, P < .007). The geometric mean antibody concentration of the group reimmunized 2 months after the first injection was higher than that in the group reimmunized after 1 month (3.95 v 2.32 µg/mL, P = .05, by analysis of covariance with age as the covariant). These data confirm our previous preliminary observations on the safety and immunogenicity of this new conjugate vaccine in infants 2 to 6 months of age. The data suggest that a 2-month interval between the first and second injections results in higher levels of serum antibody than a 1-month interval.

scholarly journals Safety, Immunogenicity, and Antibody Persistence following an Investigational Streptococcus pneumoniae and Haemophilus influenzae Triple-Protein Vaccine in a Phase 1 Randomized Controlled Study in Healthy Adults

2013 ◽  
Vol 21 (1) ◽  
pp. 56-65 ◽  
Author(s):  
Johan Berglund ◽  
Peter Vink ◽  
Fernanda Tavares Da Silva ◽  
Pascal Lestrate ◽  
Dominique Boutriau
Keyword(s):  
T Cell ◽  
Haemophilus Influenzae ◽  
Phase 1 ◽  
Geometric Mean ◽  
Controlled Study ◽  
Protein Vaccine ◽  
Serious Adverse Events ◽  
Content Type ◽  
Antibody Persistence ◽  
Systemic Symptoms

ABSTRACTWe investigated a protein-based nontypeableHaemophilus influenzae(NTHi) and pneumococcal (HiP) vaccine containing pneumococcal histidine triad D (PhtD), detoxified pneumolysin (dPly), and NTHi protein D (PD) in adults. In a phase I study, 40 healthy 18- to 40-year-old subjects were randomized (2:2:1) to receive two HiP doses administered 60 days apart, with or without AS03 adjuvant (HiP-AS and HiP groups, respectively), or Engerix B (GlaxoSmithKline, Belgium) as a control. Safety, antibodies, and antigen-specific CD4+T-cell immune responses were assessed before and until 480 days after vaccination. No serious adverse events were reported, and no subject withdrew due to an adverse event. Local and systemic symptoms were reported more frequently in the HiP-AS group than in the other two groups. The frequency and intensity of local and systemic symptoms appeared to increase after the second dose of HiP-AS or HiP but not Engerix B. Antibody geometric mean concentrations (GMCs) for PhtD, dPly, and PD increased after each dose of HiP-AS or HiP, with higher GMCs being observed in the HiP-AS group (statistically significant for anti-PD after dose 1 and anti-Ply after dose 2). GMCs remained higher at day 420 than prior to vaccination in both the HiP-AS and HiP groups. Antigen-specific CD4+T cells increased after each dose but were unmeasurable by day 480. Two doses of an investigational PhtD-dPly-PD protein vaccine induced humoral immunity and antigen-specific CD4+T-cell responses after each dose, with generally higher responses when the vaccine was administered with AS03. HiP combined with AS03 appeared to be more reactogenic than the antigens alone. (This study has been registered at ClinicalTrials.gov under registration no. NCT00814489.)

scholarly journals Stakeholder views on the acceptability of Human Infection Studies in Malawi

2019 ◽  
Author(s):  
Blessings M. Kapumba ◽  
Kondwani Jambo ◽  
Jamie Rylance ◽  
Markus Gmeiner ◽  
Rodrick Sambakunsi ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Human Infection ◽  
Stakeholder Perceptions ◽  
Ethical Challenges ◽  
Inclusion Criteria ◽  
Government Officials ◽  
District Health ◽  
Middle Income ◽  
Rural And Urban ◽  
Ongoing Assessment

Abstract Background: Human infection studies (HIS) are valuable in vaccine development. Deliberate infection, however, creates challenging questions, particularly in low and middle-income countries (LMIC) where HIS are new and ethical challenges may be heightened. Consultation with stakeholders is needed to support contextually appropriate and acceptable study design. We examined stakeholder perceptions about the acceptability and ethics of HIS in Malawi, to inform decisions about planned pneumococcal challenge research and wider understanding of HIS ethics in LMIC. Methods: We conducted 6 deliberative focus groups and 15 follow-up interviews with research staff, medical students, and community representatives from rural and urban Blantyre. We also conducted 5 key informant interviews with clinicians, ethics committee members and district health government officials. Findings: Stakeholders perceived HIS research to have potential population health benefits, but they also had concerns, particularly related to safety of volunteers and negative community reactions. Acceptability depended on a range of conditions related to procedures for voluntary and informed consent, inclusion criteria, medical care or support, compensation, regulation, and robust community engagement. These conditions largely mirror those in existing guidelines for HIS and biomedical research in LMICs. Stakeholder perceptions pointed to potential tensions, for example balancing equity, safety and relevance in inclusion criteria. Conclusions: Our findings suggest HIS research could be acceptable in Malawi, provided certain conditions are in place. Ongoing assessment of participant experiences and stakeholder perceptions will be required to strengthen HIS research during development and roll-out. Key words: Human Infection Studies, pneumococcal, Malawi, acceptability, ethics

Sign in / Sign up

Export Citation Format

Share Document