scholarly journals Reinfections in COVID-19 Patients: Impact of Virus Genetic Variability and Host Immunity

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1168
Author(s):  
Aisha Fakhroo ◽  
Hebah A. AlKhatib ◽  
Asmaa A. Al Thani ◽  
Hadi M. Yassine
Keyword(s):  
Social Life ◽  
Protective Immunity ◽  
Host Factors ◽  
Severe Illness ◽  
Rapid Decline ◽  
Rapid Spread ◽  
Antibody Titers ◽  
Variant Lineage ◽  
Humoral Responses ◽  
Induced Immunity

The COVID-19 pandemic is still posing a devastating threat to social life and economics. Despite the modest decrease in the number of cases during September–November 2020, the number of active cases is on the rise again. This increase was associated with the emergence and spread of the new SARS-CoV-2 variants of concern (VOCs), such as the U.K. (B1.1.7), South Africa (B1.351), Brazil (P1), and Indian (B1.617.2) strains. The rapid spread of these new variants has raised concerns about the multiple waves of infections and the effectiveness of available vaccines. In this review, we discuss SARS-CoV-2 reinfection rates in previously infected and vaccinated individuals in relation to humoral responses. Overall, a limited number of reinfection cases have been reported worldwide, suggesting long protective immunity. Most reinfected patients were asymptomatic during the second episode of infection. Reinfection was attributed to several viral and/or host factors, including (i) underlying immunological comorbidities; (ii) low antibody titers due to the primary infection or vaccination; (iii) rapid decline in antibody response after infection or vaccination; and (iv) reinfection with a different SARS-CoV-2 variant/lineage. Infections after vaccination were also reported on several occasions, but mostly associated with mild or no symptoms. Overall, findings suggest that infection- and vaccine-induced immunity would protect from severe illness, with the vaccine being effective against most VOCs.

scholarly journals Role of Opsonophagocytosis in Immune Protection against Malaria

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 264
Author(s):  
Wolfgang W. Leitner ◽  
Megan Haraway ◽  
Tony Pierson ◽  
Elke S. Bergmann-Leitner
Keyword(s):  
Protective Immunity ◽  
Defense Mechanisms ◽  
Vaccine Development ◽  
Immune Defense ◽  
Complement Components ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Antibody Titers ◽  
Simple Measurement ◽  
Humoral Responses

The quest for immune correlates of protection continues to slow vaccine development. To date, only vaccine-induced antibodies have been confirmed as direct immune correlates of protection against a plethora of pathogens. Vaccine immunologists, however, have learned through extensive characterizations of humoral responses that the quantitative assessment of antibody responses alone often fails to correlate with protective immunity or vaccine efficacy. Despite these limitations, the simple measurement of post-vaccination antibody titers remains the most widely used approaches for vaccine evaluation. Developing and performing functional assays to assess the biological activity of pathogen-specific responses continues to gain momentum; integrating serological assessments with functional data will ultimately result in the identification of mechanisms that contribute to protective immunity and will guide vaccine development. One of these functional readouts is phagocytosis of antigenic material tagged by immune molecules such as antibodies and/or complement components. This review summarizes our current understanding of how phagocytosis contributes to immune defense against pathogens, the pathways involved, and defense mechanisms that pathogens have evolved to deal with the threat of phagocytic removal and destruction of pathogens.

scholarly journals Anamnestic Protective Immunity to Bacillus anthracis Is Antibody Mediated but Independent of Complement and Fc Receptors

2008 ◽  
Vol 76 (5) ◽  
pp. 2177-2182 ◽  
Author(s):  
Eric T. Harvill ◽  
Manuel Osorio ◽  
Crystal L. Loving ◽  
Gloria M. Lee ◽  
Vanessa K. Kelly ◽  
...  
Keyword(s):  
T Cell ◽  
Bacillus Anthracis ◽  
Adoptive Transfer ◽  
Protective Immunity ◽  
Fc Receptors ◽  
Immunodeficient Mice ◽  
Antibody Titers ◽  
Immunocompetent Mice ◽  
Induced Immunity ◽  
Deficient Mice

ABSTRACT The threat of bioterrorist use of Bacillus anthracis has focused urgent attention on the efficacy and mechanisms of protective immunity induced by available vaccines. However, the mechanisms of infection-induced immunity have been less well studied and defined. We used a combination of complement depletion along with immunodeficient mice and adoptive transfer approaches to determine the mechanisms of infection-induced protective immunity to B. anthracis. B- or T-cell-deficient mice lacked the complete anamnestic protection observed in immunocompetent mice. In addition, T-cell-deficient mice generated poor antibody titers but were protected by the adoptive transfer of serum from B. anthracis-challenged mice. Adoptively transferred sera were protective in mice lacking complement, Fc receptors, or both, suggesting that they operate independent of these effectors. Together, these results indicate that antibody-mediated neutralization provides significant protection in B. anthracis infection-induced immunity.

scholarly journals Cord Blood-Based Approach to Assess Candidate Vaccine Adjuvants Designed for Neonates and Infants

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 95
Author(s):  
Daisuke Tokuhara ◽  
Norikatsu Hikita
Keyword(s):  
Cord Blood ◽  
Protective Immunity ◽  
Current Knowledge ◽  
Current System ◽  
Innate Immune ◽  
Vaccine Adjuvants ◽  
Adult Humans ◽  
Neonates And Infants ◽  
Induced Immunity ◽  
Review Current

Neonates and infants are particularly susceptible to infections, for which outcomes tend to be severe. Vaccination is a key strategy for preventing infectious diseases, but the protective immunity achieved through vaccination typically is weaker in infants than in healthy adults. One possible explanation for the poor acquisition of vaccine-induced immunity in infants is that their innate immune response, represented by toll-like receptors, is immature. The current system for developing pediatric vaccines relies on the confirmation of their safety and effectiveness in studies involving the use of mature animals or adult humans. However, creating vaccines for neonates and infants requires an understanding of their uniquely immature innate immunity. Here we review current knowledge regarding the innate immune system of neonates and infants and challenges in developing vaccine adjuvants for those children through analyses of cord blood.

scholarly journals Host Factors Impact Vaccine Efficacy: Implications for Seasonal and Universal Influenza Vaccine Programs

2019 ◽  
Vol 93 (21) ◽  
Author(s):  
Santosh Dhakal ◽  
Sabra L. Klein
Keyword(s):  
Influenza Virus ◽  
Influenza Vaccine ◽  
Virus Vaccine ◽  
Vaccine Efficacy ◽  
Public Health Problem ◽  
Influenza Virus Vaccine ◽  
Host Factors ◽  
Influenza Vaccines ◽  
Vaccine Type ◽  
Induced Immunity

ABSTRACT Influenza is a global public health problem. Current seasonal influenza vaccines have highly variable efficacy, and thus attempts to develop broadly protective universal influenza vaccines with durable protection are under way. While much attention is given to the virus-related factors contributing to inconsistent vaccine responses, host-associated factors are often neglected. Growing evidences suggest that host factors including age, biological sex, pregnancy, and immune history play important roles as modifiers of influenza virus vaccine efficacy. We hypothesize that host genetics, the hormonal milieu, and gut microbiota contribute to host-related differences in influenza virus vaccine efficacy. This review highlights the current insights and future perspectives into host-specific factors that impact influenza vaccine-induced immunity and protection. Consideration of the host factors that affect influenza vaccine-induced immunity might improve influenza vaccines by providing empirical evidence for optimizing or even personalizing vaccine type, dose, and use of adjuvants for current seasonal and future universal influenza vaccines.

scholarly journals pUC18-CpG Is an Effective Adjuvant for a Duck Tembusu Virus Inactivated Vaccine

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 238 ◽  
Author(s):  
Xiao Ren ◽  
Xiaolei Wang ◽  
Shan Zhang ◽  
Xintao Gao ◽  
Lichun Fang ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Protective Efficacy ◽  
Vaccine Dose ◽  
Economic Losses ◽  
Control Group ◽  
Serum Cytokines ◽  
Duck Tembusu Virus ◽  
Antibody Titers ◽  
Protection Efficacy ◽  
Tembusu Virus

Duck Tembusu virus (DTMUV) is an emerging pathogenic flavivirus responsible for massive economic losses in the duck industry. However, commercially inactivated DTMUV vaccines have been ineffective at inducing protective immunity in ducks. The widely used adjuvant cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) reportedly improve humoral and cellular immunities in animal models. However, its effectiveness in DTMUV vaccines requires validation. Here, we assessed the protective efficacy of pUC18-CpG as an adjuvant in an inactivated live DTMUV vaccine in ducks. Our results revealed that the serum hemagglutination inhibition (HI) antibody titers, positive rates of anti-DTMUV antibodies, the concentration of serum cytokines, and protection efficacy were significantly increased in ducks immunized with pUC18-CpG compared to that in the control group. Moreover, ducks immunized with a full vaccine dose containing a half dose of antigen supplemented with 40 μg of pUC18-CpG exhibited the most potent responses. This study suggests that pUC18-CpG is a promising adjuvant against DTMUV, which might prove effective in treating other viral diseases in waterfowl.

scholarly journals The Role of Virulence Proteins in Protection Conferred by Bordetella pertussis Outer Membrane Vesicle Vaccines

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 429
Author(s):  
René H. M. Raeven ◽  
Naomi van Vlies ◽  
Merijn L. M. Salverda ◽  
Larissa van der Maas ◽  
Joost P. Uittenbogaard ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Bordetella Pertussis ◽  
Protective Immunity ◽  
Membrane Vesicle ◽  
Outer Membrane Proteins ◽  
Outer Membrane Vesicle ◽  
Protective Capacity ◽  
T Helper 1 ◽  
Virulence Proteins ◽  
Humoral Responses

The limited protective immunity induced by acellular pertussis vaccines demands development of novel vaccines that induce broader and longer-lived immunity. In this study, we investigated the protective capacity of outer membrane vesicle pertussis vaccines (omvPV) with different antigenic composition in mice to gain insight into which antigens contribute to protection. We showed that total depletion of virulence factors (bvg(-) mode) in omvPV led to diminished protection despite the presence of high antibody levels. Antibody profiling revealed overlap in humoral responses induced by vaccines in bvg(-) and bvg(+) mode, but the potentially protective responses in the bvg(+) vaccine were mainly directed against virulence-associated outer membrane proteins (virOMPs) such as BrkA and Vag8. However, deletion of either BrkA or Vag8 in our outer membrane vesicle vaccines did not affect the level of protection. In addition, the vaccine-induced immunity profile, which encompasses broad antibody and mixed T-helper 1, 2 and 17 responses, was not changed. We conclude that the presence of multiple virOMPs in omvPV is crucial for protection against Bordetella pertussis. This protective immunity does not depend on individual proteins, as their absence or low abundance can be compensated for by other virOMPs.

scholarly journals 2775. Safety and Immunogenicity of a Seasonal Influenza Vaccine and Ad26.RSV.preF Vaccine With and Without Co-Administration: A Randomized, Double-Blind, Placebo-Controlled Phase 2a Study in Adults Aged ≥ 60 Years

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S979-S979
Author(s):  
Christy Comeaux ◽  
Arangassery Rosemary Bastian ◽  
Els De Paepe ◽  
Edmund Omoruyi ◽  
Wouter Haazen ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Neutralizing Antibody ◽  
Severe Illness ◽  
Tolerability Profile ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Antibody Titers ◽  
Group 2 ◽  
Tract Infections ◽  
Group 1

Abstract Background Influenza and RSV can cause respiratory tract infections leading to severe illness, hospitalization and mortality in at-risk populations, particularly the elderly. The seasonality of influenza and RSV present the potential to co-administer vaccines. This study aimed to demonstrate the non-inferiority of co-administration of the experimental RSV vaccine Ad26.RSV.preF with an influenza vaccine (Fluarix) vs. Fluarix alone in terms of immunogenicity against influenza. Methods This was a single-center, randomized, double-blind, placebo-controlled Phase 2a study (NCT03339713) in healthy adults ≥60 years old. Volunteers were randomized 1:1 to receive Fluarix + 1 × 1011 vp Ad26.RSV.preF on Day 1 and placebo on Day 29 (Group 1), or Fluarix + placebo on Day 1 and 1 × 1011 vp Ad26.RSV.preF on Day 29 (Group 2). Blood samples were taken prior to each vaccination and at Day 57. The primary endpoints were geometric mean titers (GMTs) of hemagglutination inhibition (HI) antibody titers against Fluarix strains (A/Michigan, A/Hong Kong, B/Brisbane and B/Phuket) and the safety and tolerability of Ad26.RSV.preF administered with or without Fluarix. A key secondary endpoint was neutralizing antibody titers to RSV A2. Results Volunteers (N = 180) were included in Group 1 (n = 90) or Group 2 (n = 90). Most volunteers were white (89%) and female (63%), with a median age of 65 years. Both groups exhibited an increase from baseline in HI antibody response on Day 29. The 95% one-sided upper confidence limit of all GMT ratios were below the non-inferiority margin of 2. The frequency of solicited adverse events (AE) after Ad26.RSV.preF vaccination was similar with and without influenza co-administration. Solicited AEs were mainly of Grade 1 and 2 and of transient duration. Most unsolicited AEs were considered unrelated to the study vaccination and were Grade 1 or 2. There were no serious AEs related to the study vaccine and there were no discontinuations due to AEs. RSV neutralizing antibody titers 29 days post- Ad26.RSV.preF immunization were similar in both groups (1404, Group 1; 1690, Group 2). Conclusion Co-administration of Ad26.RSV.preF with Fluarix was non-inferior to Fluarix alone in terms of immunogenicity against influenza and had an acceptable tolerability profile. Disclosures All authors: No reported disclosures.

scholarly journals 2399

2017 ◽  
Vol 1 (S1) ◽  
pp. 64-65
Author(s):  
Franchesca Garcia Robles ◽  
Nilka DeJesus ◽  
Nilka Barrios
Keyword(s):  
Cancer Therapy ◽  
Solid Tumors ◽  
Protective Immunity ◽  
Germ Cell Tumors ◽  
Hematologic Malignancies ◽  
Live Vaccines ◽  
Vaccine Preventable Diseases ◽  
Antibody Titers ◽  
Study Population ◽  
After Cancer

OBJECTIVES/SPECIFIC AIMS: Determine whether children with solid tumors maintain intact protective immunity to live vaccines during cancer therapy and after completing cancer therapy (postTx). METHODS/STUDY POPULATION: We will perform a prospective cohort study of children with solid tumors (Hodgkin lymphoma, brain, Wilms, and germ cell tumors) followed at the Puerto Rico’s University Pediatric Hospital. Protective immunity will be measured with antibody titers against live vaccines (Measles, Mumps, Rubella, and Varicella) at diagnosis, during cancer therapy, upon completion and 3 months postTx. RESULTS/ANTICIPATED RESULTS: We hypothesize that those patients with protective immunity to live vaccines prior to cancer therapy will lose it at the end of therapy. DISCUSSION/SIGNIFICANCE OF IMPACT: Loss of protective immunity to live vaccines has been reported in patients with hematologic malignancies after cancer therapy. This lack of protective immunity, which puts patients at higher risk of acquiring vaccine preventable diseases, has been limited studied in patients with solid tumors. The Center for Diseases Control has been established that it is safe to immunize cancer survivors with live vaccines 3 months post Tx. However, no clear guidelines for revaccination have been provided for this population. Understanding the protective immunity variation against live vaccines in children with solid tumors will allow us to identify the need for revaccination with live vaccines in this vulnerable population.

scholarly journals Partially Assembled K99 Fimbriae Are Required for Protection

2005 ◽  
Vol 73 (11) ◽  
pp. 7274-7280 ◽  
Author(s):  
Miguel A. Ascón ◽  
Javier Ochoa-Repáraz ◽  
Nancy Walters ◽  
David W. Pascual
Keyword(s):  
Escherichia Coli ◽  
Outer Membrane ◽  
Protective Immunity ◽  
Immunoglobulin A ◽  
Gene Clusters ◽  
T Cell Epitopes ◽  
Partial Reduction ◽  
Fimbrial Subunit ◽  
Cytokine Responses ◽  
Antibody Titers

ABSTRACTAntibodies to K99 fimbriae afford protection to F5+bovine enterotoxigenicEscherichia coli(ETEC). Previous studies show that murine dams immunized withSalmonellavaccine vectors stably expressing K99 fimbriae confer protection to ETEC-challenged neonatal pups. To begin to address adaptation of the K99 scaffold to display heterologous B- and T-cell epitopes, studies were conducted to determine how much of the assembled K99 fimbria is required to maintain protective immunity. Sequential deletions in the K99 gene clusters were made, resulting in diminished localization of the K99 fimbrial subunit in the outer membrane. As placement of the K99 fimbrial subunit became progressively contained within the vaccine vector, diminished immunoglobulin A (IgA) and IgG1 antibody titers, as well as diminished Th2-type cytokine responses, were observed in orally immunized mice. Deletion offanGH, which greatly reduced the export of the fimbrial subunit to the outer membrane, showed only partial reduction in protective immunity. By contrast, deletion offanDEFGH, which also reduced the export of the fimbrial subunit to the outer membrane but retained more subunit in the cytoplasm, resulted in protective immunity being dramatically reduced. Thus, these studies showed that retention of K99 fimbrial subunit as native fimbriae or with the deletion offanGHis sufficient to confer protection.

scholarly journals Viral and host factors related to the clinic outcome of the SARS-CoV-2 infection

2020 ◽  
Author(s):  
Xiaonan Zhang ◽  
Yun Tan ◽  
Yun Ling ◽  
Gang Lu ◽  
Feng Liu ◽  
...  
Keyword(s):  
Host Factors ◽  
Wuhan City ◽  
Cell Counts ◽  
Disease Outcomes ◽  
Rapid Spread ◽  
Differential Exposure ◽  
Critical Patients ◽  
Global Initiative ◽  
Novel Coronavirus ◽  
High Level

Abstract At least three months have been passed since the outbreak of the severe acute respiratory disease, COVID-19 in Wuhan city, China in December 2019, caused by the infection of a novel coronavirus, SARS-CoV-2.1,2. Due to its rapid spread throughout China and abroad, knowledge sharing for both its epidemiology and clinic manifestations is urgently need. Here we analyzed the clinical, molecular and immunological data from 326 confirmed cases of SARS-CoV-2 infection in Shanghai. Genomic sequences assembled from 112 quality samples together with uploaded sequences in Global Initiative on Sharing All Influenza Data (GISAID) showed a stable evolution and suggested two major lineages with differential exposure history during the earliest outbreak in Wuhan. Nevertheless, they exhibited similar virulence and clinical outcomes. Lymphocytopenia, especially the reduced CD4+ and CD8+ T cell counts upon admission, was predictive of disease progression. High level of IL-6 and IL-8 during treatment was observed in severe and critical patients and correlated with decreased lymphocyte count. The determinants of disease severity seemed to stem mostly from host factors such age, lymphocytopenia and its associated cytokine storm whereas viral genetic variation did not significantly affect the outcomes. This comprehensive analysis on the molecular, immunological and clinical data provides a panorama of the key determinants related to the disease outcomes which should be helpful for improving the current combat against this extremely aggressive pandemic.Authors Xiaonan Zhang, Yun Tan, Yun Ling, Gang Lu, Feng Liu, and Zhigang Yi contributed equally to this work.

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