Clinical And Vaccine Immunology[JOURNAL]
Sun
200 papers
Parasitic Infections in Pregnancy Decrease Placental Transfer of Antipneumococcus Antibodies.
McKittrick ND, Vu DM, Malhotra I … +3 more , King CH, Mutuku F, LaBeaud AD
Clin Vaccine Immunol · 2017 Jun · PMID 28404574 · Full text
Many factors can influence maternal placental antibody transfer to the fetus, which confers important immune protection to the newborn infant. However, little is known about the effect of maternal parasitic infection on...
Many factors can influence maternal placental antibody transfer to the fetus, which confers important immune protection to the newborn infant. However, little is known about the effect of maternal parasitic infection on placental antibody transfer. To investigate this, we selected from a parent study of 576 pregnant Kenyan women four groups of women with term deliveries (≥37 weeks), including uninfected women ( = 30) and women with solo infections with malaria ( = 30), hookworm ( = 30), or schistosomiasis ( = 10). Maternal plasma at delivery and infant cord blood were tested via multiplex fluorescent bead assay for IgG against 10 pneumococcal serotypes (PnPs 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F), diphtheria toxoid, and type B. Infants born to mothers with prenatal malaria, hookworm, or infections were associated with a significantly reduced ratio of maternal to infant cord blood antibody concentration for serotypes 1, 4, 5, 6B, 7F, 9V, and 18C compared to infants of uninfected mothers. Anti-diphtheria toxoid and anti- type B IgG ratios were not significantly different among infection groups. Prenatal parasitic infections decrease the transfer of maternal IgG antibodies to infants for several serotypes of .
Cytomegalovirus Virions Shed in Urine Have a Reversible Block to Epithelial Cell Entry and Are Highly Resistant to Antibody Neutralization.
Cui X, Adler SP, Schleiss MR … +3 more , Arav-Boger R, Demmler Harrison GJ, McVoy MA
Clin Vaccine Immunol · 2017 Jun · PMID 28404573 · Full text
Cytomegalovirus (CMV) causes sensorineural hearing loss and developmental disabilities in newborns when infections are acquired Pregnant women may acquire CMV from oral exposure to CMV in urine or saliva from young chil...
Cytomegalovirus (CMV) causes sensorineural hearing loss and developmental disabilities in newborns when infections are acquired Pregnant women may acquire CMV from oral exposure to CMV in urine or saliva from young children. Neutralizing antibodies in maternal saliva have the potential to prevent maternal infection and, in turn, fetal infection. As CMV uses different viral glycoprotein complexes to enter different cell types, the first cells to be infected in the oral cavity could determine the type of antibodies needed to disrupt oral transmission. Antibodies targeting the pentameric complex (PC) should block CMV entry into epithelial cells but not into fibroblasts or Langerhans cells (which do not require the PC for entry), while antibodies targeting glycoprotein complexes gB or gH/gL would be needed to block entry into fibroblasts, Langerhans cells, or other cell types. To assess the potential for antibodies to disrupt oral acquisition, CMV from culture-positive urine samples (uCMV) was used to study cell tropisms and sensitivity to antibody neutralization. uCMV entered epithelial cells poorly compared with the entry into fibroblasts. CMV-hyperimmune globulin or monoclonal antibodies targeting gB, gH/gL, or the PC were incapable of blocking the entry of uCMV into either fibroblasts or epithelial cells. Both phenotypes were lost after one passage in cultured fibroblasts, suggestive of a nongenetic mechanism. These results suggest that uCMV virions have a reversible block to epithelial cell entry. Antibodies may be ineffective in preventing maternal oral CMV acquisition but may limit viral spread in blood or tissues, thereby reducing or preventing fetal infection and disease.
An HIV Envelope gp120-Fc Fusion Protein Elicits Effector Antibody Responses in Rhesus Macaques.
Shubin Z, Li W, Poonia B … +5 more , Ferrari G, LaBranche C, Montefiori D, Zhu X, Pauza CD
Clin Vaccine Immunol · 2017 Jun · PMID 28404572 · Full text
A goal for HIV prevention programs is to develop safe, effective vaccines that elicit durable and broadly protective antibodies. Many vaccine programs focus on the immune responses to critical epitopes in the gp120 porti...
A goal for HIV prevention programs is to develop safe, effective vaccines that elicit durable and broadly protective antibodies. Many vaccine programs focus on the immune responses to critical epitopes in the gp120 portion of HIV envelope glycoprotein (Env) and seek to improve the quality and quantity of antibodies by altering the sequence, conformation, oligomerization, or glycosylation of gp120 to activate appropriate germ line B cells and mimic the subsequent maturation pathways seen in infected individuals. As a complement to these strategies, we developed dimeric fusion protein immunogens consisting of HIV gp120 monomer attached to a Gly/Ser linker that is, in turn, fused to one half of the dimeric Fc domain from rhesus macaque IgG1 (Env-rFc). We envisioned that Env-rFc may mimic some aspects of immune complexes by binding Fc gamma receptors (FcγRs) on immune cells to increase the strength, breadth, and durability of Env-specific antibody responses. The Env-rFc retained a capacity to bind both cell surface CD4 and FcγRs. In a rhesus macaque immunization study, Env-rFc elicited higher gp120 binding antibody titers than Env and elicited antibodies that recognize CD4-induced epitopes. Env-rFc also induced antibodies capable of neutralizing tier 1A HIV pseudotyped viruses and mediating antibody-dependent cellular cytotoxicity, outcomes not observed with monomeric gp120 in our study. Serum antibodies produced in Env-rFc-immunized macaques had increased durability compared to that of Env monomer immunization. Our work suggests that adding IgG1 Fc to Env-based immunogens may stimulate increased effector capacity in the immune sera and improve the protective serum antibody response.
Early Detection of Circulating Antigen and IgM-Associated Immune Complexes during Experimental Mycobacterium bovis Infection in Cattle.
Lyashchenko KP, Greenwald R, Sikar-Gang A … +8 more , Sridhara AA, Johnathan A, Lambotte P, Esfandiari J, Maggioli MF, Thacker TC, Palmer MV, Waters WR
Clin Vaccine Immunol · 2017 Jun · PMID 28404571 · Full text
The presence of circulating antigen in cattle experimentally infected with was demonstrated using dual-path platform (DPP) technology. The antigen capture immunoassays employed rabbit polyclonal antibody recognizing pre...
The presence of circulating antigen in cattle experimentally infected with was demonstrated using dual-path platform (DPP) technology. The antigen capture immunoassays employed rabbit polyclonal antibody recognizing predominantly complex-specific epitopes and were able to detect soluble substances and whole cells of mycobacteria. The antigen found in serum appeared to be mostly bound to IgM, but not to IgG, within the immune complexes formed at early stages of infection. The antigen was also detected in bile and urine, indicating possible clearance pathways. The data correlation analyses supported the idea of the role of IgM responses in antigen persistence during infection. The antigen was detectable in serum months prior to detectable antibody seroconversion. This proof-of-concept study suggested the potential for improved immunodiagnostics for bovine tuberculosis.
Decreased Vector Gene Expression from E2b Gene-Deleted Adenovirus Serotype 5 Vaccines Intensifies Proinflammatory Immune Responses.
Quiroga D, Aldhamen YA, Godbehere S … +2 more , Harding L, Amalfitano A
Clin Vaccine Immunol · 2017 Jun · PMID 28381403 · Full text
Recombinant adenovirus serotype 5 (Ad5) vectors are promising vaccine candidates due to their intrinsic immunogenicity and potent transgene expression; however, widespread preexisting Ad5 immunity has been considered a d...
Recombinant adenovirus serotype 5 (Ad5) vectors are promising vaccine candidates due to their intrinsic immunogenicity and potent transgene expression; however, widespread preexisting Ad5 immunity has been considered a developmental impediment to the use of traditional, or conventional, E1 and E3 gene-deleted Ad5 (Ad5[E1-]) vaccines. Even in the presence of anti-Ad5 immunity, recent murine and human studies have confirmed E2b gene-deleted Ad5 (Ad5[E1-,E2b-]) vaccines to be highly efficacious inducers of transgene-specific memory responses and significantly less toxic options than Ad5[E1-] vaccines. While these findings have been substantially confirmed, the molecular mechanisms underlying the different reactions to these vaccine platforms are unknown. Using cultures of human peripheral blood mononuclear cells (hPBMCs) derived from multiple human donors, we found that Ad5[E1-,E2b-] vaccines trigger higher levels of hPBMC proinflammatory cytokine secretion than Ad5[E1-] vaccines. Interestingly, these responses were generated regardless of the donors' preexisting anti-Ad5 humoral and cell-mediated immune response status. hPBMC infection with the Ad5[E1-,E2b-] vaccine also provoked greater Th1-dominant gene responses yet smaller amounts of Ad-derived gene expression than Ad5[E1-] vaccines. These results suggest that Ad5[E1-,E2b-] vaccines, in contrast to Ad5[E1-] vaccines, do not promote activities that suppress innate immune signaling, thereby allowing for improved vaccine efficacy and a superior safety profile independently of previous Ad5 immunity.
Transcutaneous Immunization with a Band-Aid Prevents Experimental Otitis Media in a Polymicrobial Model.
Novotny LA, Clements JD, Goodman SD … +1 more , Bakaletz LO
Clin Vaccine Immunol · 2017 Jun · PMID 28381402 · Full text
Otitis media (OM) is a common pediatric disease, and nontypeable (NTHI) is the predominant pathogen in chronic OM, recurrent OM, and OM associated with treatment failure. OM is also a polymicrobial disease, wherein an u...
Otitis media (OM) is a common pediatric disease, and nontypeable (NTHI) is the predominant pathogen in chronic OM, recurrent OM, and OM associated with treatment failure. OM is also a polymicrobial disease, wherein an upper respiratory tract viral infection predisposes to ascension of NTHI from the nasopharynx, the site of colonization, to the normally sterile middle ear, resulting in disease. Using a clinically relevant viral-bacterial coinfection model of NTHI-induced OM, we performed transcutaneous immunization (TCI) via a band-aid delivery system to administer each of three promising NTHI vaccine candidates derived from bacterial adhesive proteins and biofilm mediators: recombinant soluble PilA (rsPilA), chimV4, and integration host factor. Each immunogen was admixed with the adjuvant LT(R192G/L211A), a double mutant of heat-labile enterotoxin, and assessed for relative ability to prevent the onset of experimental OM. For each cohort, the presence of circulating immunogen-specific antibody-secreting cells and serum antibody was confirmed prior to intranasal NTHI challenge. After bacterial challenge, blinded video otoscopy and tympanometry revealed a significant reduction in the proportion of animals with signs of OM compared to levels in animals receiving adjuvant only, with an overall vaccine efficacy of 64 to 77%. These data are the first to demonstrate the efficacy afforded by TCI with a band-aid vaccine delivery system in a clinically relevant polymicrobial model of OM. The simplicity of TCI with a band-aid and the significant efficacy observed here hold great promise for reducing the global burden of OM in the pediatric population.
Exploring Human Antimicrobial Antibody Responses on a Single B Cell Level.
Hofmann D, Lai JR
Clin Vaccine Immunol · 2017 May · PMID 28356257 · Full text
Analysis of monoclonal antibodies (MAbs) derived from single B cell cloning has been highly beneficial for antimicrobial immunotherapy, vaccine design, and advancing our understanding of pathogen-triggered effects on the...
Analysis of monoclonal antibodies (MAbs) derived from single B cell cloning has been highly beneficial for antimicrobial immunotherapy, vaccine design, and advancing our understanding of pathogen-triggered effects on the human immunoglobulin repertoire. Sequencing of variable domains of single B cells, and characterization of binding and functional activities of MAbs derived from those sequences, provides in-depth insight not only into sites of susceptibility for antibody-mediated neutralization or opsonization of the pathogen but also into the dynamics of protective antibody evolution during infection. This information can be utilized to rapidly develop novel immunotherapies of completely human origin and provides a roadmap for structure-based vaccine design that aims to elicit similar protective antibody responses. Here, we summarize recent aspects of the single B cell cloning approach.
Recent Progress in the Prevention of Serogroup B Meningococcal Disease.
Feavers IM, Maiden MCJ
Clin Vaccine Immunol · 2017 May · PMID 28356256 · Full text
The widespread use of meningococcal polysaccharide conjugate vaccines has highlighted the challenge of providing protection against serogroup B disease. Over a period of 4 decades, vaccine development has focused on subc...
The widespread use of meningococcal polysaccharide conjugate vaccines has highlighted the challenge of providing protection against serogroup B disease. Over a period of 4 decades, vaccine development has focused on subcapsular protein antigens, first with outer membrane vesicle (OMV) vaccines against epidemic outbreaks, and more recently on new multicomponent vaccines designed to offer better cross-protection against the antigenically diverse strains responsible for endemic disease. Because of the low incidence of meningococcal disease, the protective efficacy of these vaccines has not been determined in clinical studies, and their licensure has been based on serological data; however, the serological assays used to predict protective coverage have limitations. As a result, evidence of the effectiveness of these vaccines against different strains and the contribution of specific antigens to protection can only be provided by epidemiological analyses following their implementation in sufficiently large populations. The recent inclusion of the four-component meningococcal serogroup B (4CMenB) vaccine, Bexsero, in the infant immunization program in the UK has provided preliminary evidence that the vaccine is effective. Ongoing surveillance will provide valuable data on its longer-term impact and antigenic coverage. Further development of protein-based vaccines against meningococcal disease is anticipated to improve antigenic coverage and adjust to changes in circulating strains. At the same time, alternative immunization strategies may be explored to improve overall vaccine effectiveness by, for example, protecting the youngest infants or providing herd protection.
Characterization and Vaccine Potential of Membrane Vesicles Produced by Francisella noatunensis subsp. orientalis in an Adult Zebrafish Model.
Lagos L, Tandberg JI, Repnik U … +5 more , Boysen P, Ropstad E, Varkey D, Paulsen IT, Winther-Larsen HC
Clin Vaccine Immunol · 2017 May · PMID 28331079 · Full text
Vaccine development against extracellular bacteria has been important for the sustainability of the aquaculture industry. In contrast, infections with intracellular pathogens remain largely an unresolved problem. subsp....
Vaccine development against extracellular bacteria has been important for the sustainability of the aquaculture industry. In contrast, infections with intracellular pathogens remain largely an unresolved problem. subsp. is a Gram-negative, facultative intracellular bacterium that causes the disease francisellosis in fish. Francisellosis is commonly characterized as a chronic granulomatous disease with high morbidity and can result in high mortality depending on the host. In this study, we explored the potential of bacterial membrane vesicles (MVs) as a vaccine agent against subsp. Bacterial MVs are spherical structures naturally released from the membrane of bacteria and are often enriched with selected bacterial components such as toxins and signaling molecules. MVs were isolated from broth-cultured subsp. in the present work, and proteomic analysis by mass spectrometry revealed that MVs contained a variety of immunogenic factors, including the intracellular growth proteins IglC and IglB, known to be part of a pathogenicity island (FPI), as well as outer membrane protein OmpA, chaperonin GroEL, and chaperone ClpB. By using flow cytometry and electron microscopy, we observed that subsp. mainly infects myelomonocytic cells, both and Immunization with MVs isolated from subsp. protects zebrafish from subsequent challenge with a lethal dose of subsp. To determine if MVs induce a typical acute inflammatory response, mRNA expression levels were assessed by quantitative real-time PCR. Expression of , , and , as well as , , and , was upregulated, thus confirming the immunogenic properties of subsp. -derived MVs.
Tuberculin Skin Testing Boosts Interferon Gamma Responses to DIVA Reagents in Mycobacterium bovis-Infected Cattle.
Jones GJ, Coad M, Khatri B … +6 more , Bezos J, Parlane NA, Buddle BM, Villarreal-Ramos B, Hewinson RG, Vordermeier HM
Clin Vaccine Immunol · 2017 May · PMID 28331078 · Full text
BCG vaccination sensitizes cattle to bovine tuberculin, which compromises the use of the current bovine tuberculosis (TB) surveillance tests. Although the performance of a blood test (that utilizes antigens expressed by...
BCG vaccination sensitizes cattle to bovine tuberculin, which compromises the use of the current bovine tuberculosis (TB) surveillance tests. Although the performance of a blood test (that utilizes antigens expressed by but not by BCG) capable of discriminating infected from vaccinated animals (DIVA interferon gamma test [DIT]) has been evaluated in naturally infected TB field reactors, there is a need to perform similar analysis in a BCG-vaccinated -infected population. Furthermore, we explored different scenarios under which a DIT may be implemented alongside BCG vaccination: (i) serial testing to resolve potential false-positive skin test results or (ii) a standalone test to replace the single intradermal comparative cervical tuberculin (SICCT) skin test. Our results demonstrated significantly better relative test sensitivity when the DIT was evaluated in a serial test scenario. Direct comparison of pre- and post-skin test blood samples revealed that the SICCT test induced significant boosting of the gamma interferon response in -infected animals to both the ESAT-6-CFP-10 and Rv3615c peptide cocktails that comprise the DIT, which persisted for the ESAT-6-CFP-10 reagent for at least 14 days. Importantly, no similar boosting effects were observed in noninfected BCG vaccinates, suggesting that DIVA blood testing after a recent skin test would have minimal impact on test specificity.
Novel Mechanisms Revealed in the Trachea Transcriptome of Resistant and Susceptible Chicken Lines following Infection with Newcastle Disease Virus.
Deist MS, Gallardo RA, Bunn DA … +4 more , Kelly TR, Dekkers JCM, Zhou H, Lamont SJ
Clin Vaccine Immunol · 2017 May · PMID 28331077 · Full text
Newcastle disease virus (NDV) has a devastating impact on poultry production in developing countries. This study examined the transcriptome of tracheal epithelial cells from two inbred chicken lines that differ in NDV su...
Newcastle disease virus (NDV) has a devastating impact on poultry production in developing countries. This study examined the transcriptome of tracheal epithelial cells from two inbred chicken lines that differ in NDV susceptibility after challenge with a high-titer inoculum of lentogenic NDV. The Fayoumi line had a significantly lower NDV load postchallenge than the Leghorn line, demonstrating the Fayoumi line's classification as a relatively NDV-resistant breed. Examination of the trachea transcriptome showed a large increase in immune cell infiltration in the trachea in both lines at all times postinfection. The pathways conserved across lines and at all three time points postinfection included iCOS-iCOSL signaling in T helper cells, NF-κB signaling, the role of nuclear factor of activated T cells in the regulation of the immune response, calcium-induced T lymphocyte apoptosis, phospholipase C signaling, and CD28 signaling in T helper cells. Although shared pathways were seen in the Fayoumi and Leghorn lines, each line showed unique responses as well. The downregulation of collagen and the activation of eukaryotic translation initiation factor 2 signaling in the Fayoumis relative to the Leghorns at 2 days postinfection may contribute to the resistance phenotype seen in the Fayoumis. This study provides a further understanding of host-pathogen interactions which could improve vaccine efficacy and, in combination with genome-wide association studies, has the potential to advance strategies for breeding chickens with enhanced resistance to NDV.
Plasmablast Response to Primary Rhesus Cytomegalovirus (CMV) Infection in a Monkey Model of Congenital CMV Transmission.
Fan Q, Nelson CS, Bialas KM … +15 more , Chiuppesi F, Amos J, Gurley TC, Marshall DJ, Eudailey J, Heimsath H, Himes J, Deshpande A, Walter MR, Wussow F, Diamond DJ, Barry PA, Moody MA, Kaur A, Permar SR
Clin Vaccine Immunol · 2017 May · PMID 28298291 · Full text
Human cytomegalovirus (HCMV) is the most common congenital infection worldwide and the leading infectious cause of neurologic deficits and hearing loss in newborns. Development of a maternal HCMV vaccine to prevent verti...
Human cytomegalovirus (HCMV) is the most common congenital infection worldwide and the leading infectious cause of neurologic deficits and hearing loss in newborns. Development of a maternal HCMV vaccine to prevent vertical virus transmission is a high priority, yet protective maternal immune responses following acute infection are poorly understood. To characterize the maternal humoral immune response to primary CMV infection, we investigated the plasmablast and early antibody repertoire using a nonhuman primate model with two acutely rhesus CMV (RhCMV)-infected animals-a CD4 T cell-depleted dam that experienced fetal loss shortly after vertical RhCMV transmission and an immunocompetent dam that did not transmit RhCMV to her infant. Compared to the CD4 T cell-depleted dam that experienced fetal loss, the immunocompetent, nontransmitting dam had a more rapid and robust plasmablast response that produced a high proportion of RhCMV-reactive antibodies, including the first identified monoclonal antibody specific for soluble and membrane-associated RhCMV envelope glycoprotein B (gB). Additionally, we noted that plasmablast RhCMV-specific antibodies had variable gene usage and maturation similar to those observed in a monkey chronically coinfected with simian immunodeficiency virus (SIV) and RhCMV. This study reveals characteristics of the early maternal RhCMV-specific humoral immune responses to primary RhCMV infection in rhesus monkeys and may contribute to a future understanding of what antibody responses should be targeted by a vaccine to eliminate congenital HCMV transmission. Furthermore, the identification of an RhCMV gB-specific monoclonal antibody underscores the possibility of modeling future HCMV vaccine strategies in this nonhuman primate model.
A Prime/Boost PfCS14K/MVA-sPfCS Vaccination Protocol Generates Robust CD8 T Cell and Antibody Responses to Plasmodium falciparum Circumsporozoite Protein and Protects Mice against Malaria.
Vijayan A, Mejías-Pérez E, Espinosa DA … +4 more , Raman SC, Sorzano COS, Zavala F, Esteban M
Clin Vaccine Immunol · 2017 May · PMID 28298290 · Full text
Vaccines against the preerythrocytic stages of malaria are appealing because the parasite can be eliminated before disease onset and because they offer the unique possibility of targeting the parasite with both antibodie...
Vaccines against the preerythrocytic stages of malaria are appealing because the parasite can be eliminated before disease onset and because they offer the unique possibility of targeting the parasite with both antibodies and T cells. Although the role of CD8 T cells in preerythrocytic malaria stages is well documented, a highly effective T cell-inducing vaccine remains to be advanced. Here we report the development of a prime-boost immunization regimen with the circumsporozoite protein (PfCS) fused to the oligomer-forming vaccinia virus A27 protein and a modified vaccinia virus Ankara (MVA) vector expressing PfCS. This protocol induced polyfunctional CD8 T cells with an effector memory phenotype and high PfCS antibody levels. These immune responses correlated with inhibition of liver-stage parasitemia in 80% and sterile protection in 40% of mice challenged with a transgenic parasite line that expressed PfCS. Our findings underscore the potential of T and B cell immunization strategies for improving protective effectiveness against malaria.
Mass Spectrometry Approaches for Identification and Quantitation of Therapeutic Monoclonal Antibodies in the Clinical Laboratory.
Ladwig PM, Barnidge DR, Willrich MAV
Clin Vaccine Immunol · 2017 May · PMID 28274937 · Full text
Therapeutic monoclonal antibodies (MAbs) are an important class of drugs used to treat diseases ranging from autoimmune disorders to B cell lymphomas to other rare conditions thought to be untreatable in the past. Many a...
Therapeutic monoclonal antibodies (MAbs) are an important class of drugs used to treat diseases ranging from autoimmune disorders to B cell lymphomas to other rare conditions thought to be untreatable in the past. Many advances have been made in the characterization of immunoglobulins as a result of pharmaceutical companies investing in technologies that allow them to better understand MAbs during the development phase. Mass spectrometry is one of the new advancements utilized extensively by pharma to analyze MAbs and is now beginning to be applied in the clinical laboratory setting. The rise in the use of therapeutic MAbs has opened up new challenges for the development of assays for monitoring this class of drugs. MAbs are larger and more complex than typical small-molecule therapeutic drugs routinely analyzed by mass spectrometry. In addition, they must be quantified in samples that contain endogenous immunoglobulins with nearly identical structures. In contrast to an enzyme-linked immunosorbent assay (ELISA) for quantifying MAbs, mass spectrometry-based assays do not rely on MAb-specific reagents such as recombinant antigens and/or anti-idiotypic antibodies, and time for development is usually shorter. Furthermore, using molecular mass as a measurement tool provides increased specificity since it is a first-order principle unique to each MAb. This enables rapid quantification of MAbs and multiplexing. This review describes how mass spectrometry can become an important tool for clinical chemists and especially immunologists, who are starting to develop assays for MAbs in the clinical laboratory and are considering mass spectrometry as a versatile platform for the task.
Tuberculous Lymphadenitis Is Associated with Enhanced Baseline and Antigen-Specific Induction of Type 1 and Type 17 Cytokines and Reduced Interleukin-1β (IL-1β) and IL-18 at the Site of Infection.
Kathamuthu GR, Moideen K, Baskaran D … +9 more , Banurekha VV, Nair D, Sekar G, Sridhar R, Vidyajayanthi B, Gajendraraj G, Parandhaman DK, Srinivasan A, Babu S
Clin Vaccine Immunol · 2017 May · PMID 28249842 · Full text
Tuberculous lymphadenitis (TBL) is characterized by an expansion of Th1 and Th17 cells with altered serum levels of proinflammatory cytokines. However, the cytokine profile at the site of infection, i.e., the affected ly...
Tuberculous lymphadenitis (TBL) is characterized by an expansion of Th1 and Th17 cells with altered serum levels of proinflammatory cytokines. However, the cytokine profile at the site of infection, i.e., the affected lymph nodes, has not been examined in detail. To estimate the baseline and mycobacterial antigen-stimulated concentrations of type 1, type 17, and other proinflammatory cytokines in patients with TBL ( = 14), we examined both the baseline and the antigen-specific concentrations of these cytokines before and after chemotherapy and compared them with those in individuals with pulmonary tuberculosis (PTB) ( = 14). In addition, we also compared the cytokine responses in whole blood and those in the lymph nodes of TBL individuals. We observed significantly enhanced baseline and antigen-specific levels of type 1 cytokines (gamma interferon [IFN-γ] and tumor necrosis factor alpha [TNF-α]) and a type 17 cytokine (interleukin-17 [IL-17]) and significantly diminished baseline and antigen-specific levels of proinflammatory cytokines (IL-1β and IL-18) in the whole blood of TBL individuals compared to those in the whole blood of PTB individuals. Moreover, we also observed a pattern of baseline and antigen-specific cytokine production at the site of infection (lymph node) similar to that in the whole blood of TBL individuals. Following standard antituberculosis (anti-TB) treatment, we observed alterations in the baseline and/or antigen-specific levels of IFN-γ, TNF-α, IL-1β, and IL-18. TBL is therefore characterized by enhanced baseline and antigen-specific production of type 1 and type 17 cytokines and reduced baseline and antigen-specific production of IL-1β and IL-18 at the site of infection.
B-Cell Responses to Intramuscular Administration of a Bivalent Virus-Like Particle Human Norovirus Vaccine.
Ramani S, Neill FH, Ferreira J … +9 more , Treanor JJ, Frey SE, Topham DJ, Goodwin RR, Borkowski A, Baehner F, Mendelman PM, Estes MK, Atmar RL
Clin Vaccine Immunol · 2017 May · PMID 28249841 · Full text
Human noroviruses (HuNoVs) are a leading cause of acute gastroenteritis worldwide. A virus-like particle (VLP) candidate vaccine induces the production of serum histo-blood group antigen (HBGA)-blocking antibodies, the f...
Human noroviruses (HuNoVs) are a leading cause of acute gastroenteritis worldwide. A virus-like particle (VLP) candidate vaccine induces the production of serum histo-blood group antigen (HBGA)-blocking antibodies, the first identified correlate of protection from HuNoV gastroenteritis. Recently, virus-specific IgG memory B cells were identified to be another potential correlate of protection against HuNoV gastroenteritis. We assessed B-cell responses following intramuscular administration of a bivalent (genogroup I, genotype 1 [GI.1]/genogroup II, genotype 4 [GII.4]) VLP vaccine using protocols identical to those used to evaluate cellular immunity following experimental GI.1 HuNoV infection. The kinetics and magnitude of cellular immunity to G1.1 infection were compared to those after VLP vaccination. Intramuscular immunization with the bivalent VLP vaccine induced the production of antibody-secreting cells (ASCs) and memory B cells. ASC responses peaked at day 7 after the first dose of vaccine and returned to nearly baseline levels by day 28. Minimal increases in ASCs were seen after a second vaccine dose at day 28. Antigen-specific IgG memory B cells persisted at day 180 postvaccination for both GI.1 and GII.4 VLPs. The overall trends in B-cell responses to vaccination were similar to the trends in the responses to infection, where there was a greater bias of an ASC response toward IgA and a memory B-cell response to IgG. The magnitude of the ASC and memory B-cell responses to the GI.1 VLP component of the vaccine was also comparable to that of the responses following GI.1 infection. The production of IgG memory B cells and persistence at day 180 is a key finding and underscores the need for future studies to determine if IgG memory B cells are a correlate of protection following vaccination. (This study has been registered at ClinicalTrials.gov under registration no. NCT01168401.).
Antibody Responses to Zika Virus Infections in Environments of Flavivirus Endemicity.
Keasey SL, Pugh CL, Jensen SMR … +6 more , Smith JL, Hontz RD, Durbin AP, Dudley DM, O'Connor DH, Ulrich RG
Clin Vaccine Immunol · 2017 Apr · PMID 28228395 · Full text
Zika virus (ZIKV) infections occur in areas where dengue virus (DENV), West Nile virus (WNV), yellow fever virus (YFV), and other viruses of the genus cocirculate. The envelope (E) proteins of these closely related flav...
Zika virus (ZIKV) infections occur in areas where dengue virus (DENV), West Nile virus (WNV), yellow fever virus (YFV), and other viruses of the genus cocirculate. The envelope (E) proteins of these closely related flaviviruses induce specific long-term immunity, yet subsequent infections are associated with cross-reactive antibody responses that may enhance disease susceptibility and severity. To gain a better understanding of ZIKV infections against a background of similar viral diseases, we examined serological immune responses to ZIKV, WNV, DENV, and YFV infections of humans and nonhuman primates (NHPs). Using printed microarrays, we detected very specific antibody responses to primary infections with probes of recombinant E proteins from 15 species and lineages of flaviviruses pathogenic to humans, while high cross-reactivity between ZIKV and DENV was observed with 11 printed native viruses. Notably, antibodies from human primary ZIKV or secondary DENV infections that occurred in areas where flavivirus is endemic broadly recognized E proteins from many flaviviruses, especially DENV, indicating a strong influence of infection history on immune responses. A predictive algorithm was used to tentatively identify previous encounters with specific flaviviruses based on serum antibody interactions with the multispecies panel of E proteins. These results illustrate the potential impact of exposure to related viruses on the outcome of ZIKV infection and offer considerations for development of vaccines and diagnostics.
Update on Chlamydia trachomatis Vaccinology.
de la Maza LM, Zhong G, Brunham RC
Clin Vaccine Immunol · 2017 Apr · PMID 28228394 · Full text
Attempts to produce a vaccine to protect against -induced trachoma were initiated more than 100 years ago and continued for several decades. Using whole organisms, protective responses were obtained. However, upon exposu...
Attempts to produce a vaccine to protect against -induced trachoma were initiated more than 100 years ago and continued for several decades. Using whole organisms, protective responses were obtained. However, upon exposure to , disease exacerbation developed in some immunized individuals, precluding the implementation of the vaccine. Evidence of the role of as a sexually transmitted pathogen started to emerge in the 1960s, and it soon became evident that it can cause acute infections and long-term sequelae in women, men, and newborns. The main focus of this minireview is to summarize recent findings and discuss formulations, including antigens, adjuvants, routes, and delivery systems for immunization, primarily explored in the female mouse model, with the goal of implementing a vaccine against genital infections.
A Plasmodium vivax Plasmid DNA- and Adenovirus-Vectored Malaria Vaccine Encoding Blood-Stage Antigens AMA1 and MSP1 in a Prime/Boost Heterologous Immunization Regimen Partially Protects Aotus Monkeys against Blood-Stage Challenge.
Obaldia N, Stockelman MG, Otero W … +9 more , Cockrill JA, Ganeshan H, Abot EN, Zhang J, Limbach K, Charoenvit Y, Doolan DL, Tang DC, Richie TL
Clin Vaccine Immunol · 2017 Apr · PMID 28179404 · Full text
Malaria is caused by parasites of the genus , which are transmitted to humans by the bites of mosquitoes. After the elimination of , it is predicted that will remain an important cause of morbidity and mortality outsid...
Malaria is caused by parasites of the genus , which are transmitted to humans by the bites of mosquitoes. After the elimination of , it is predicted that will remain an important cause of morbidity and mortality outside Africa, stressing the importance of developing a vaccine against malaria. In this study, we assessed the immunogenicity and protective efficacy of two antigens, apical membrane antigen 1 (AMA1) and the 42-kDa C-terminal fragment of merozoite surface protein 1 (MSP1) in a plasmid recombinant DNA prime/adenoviral (Ad) vector boost regimen in monkeys. Groups of 4 to 5 monkeys were immunized with plasmid DNA alone, Ad alone, prime/boost regimens with each antigen, prime/boost regimens with both antigens, and empty vector controls and then subjected to blood-stage challenge. The heterologous immunization regimen with the antigen pair was more protective than either antigen alone or both antigens delivered with a single vaccine platform, on the basis of their ability to induce the longest prepatent period and the longest time to the peak level of parasitemia, the lowest peak and mean levels of parasitemia, the smallest area under the parasitemia curve, and the highest self-cure rate. Overall, prechallenge MSP1 antibody titers strongly correlated with a decreased parasite burden. Nevertheless, a significant proportion of immunized animals developed anemia. In conclusion, the plasmid DNA/Ad serotype 5 vaccine encoding blood-stage parasite antigens AMA1 and MSP1 in a heterologous prime/boost immunization regimen provided significant protection against blood-stage challenge in monkeys, indicating the suitability of these antigens and this regimen for further development.
Evaluation of Plasmodium vivax Cell-Traversal Protein for Ookinetes and Sporozoites as a Preerythrocytic P. vivax Vaccine.
Alves E, Salman AM, Leoratti F … +9 more , Lopez-Camacho C, Viveros-Sandoval ME, Lall A, El-Turabi A, Bachmann MF, Hill AV, Janse CJ, Khan SM, Reyes-Sandoval A
Clin Vaccine Immunol · 2017 Apr · PMID 28179403 · Full text
Four different vaccine platforms, each targeting the human malaria parasite cell-traversal protein for ookinetes and sporozoites (CelTOS), were generated and assessed for protective efficacy. These platforms consisted o...
Four different vaccine platforms, each targeting the human malaria parasite cell-traversal protein for ookinetes and sporozoites (CelTOS), were generated and assessed for protective efficacy. These platforms consisted of a recombinant chimpanzee adenoviral vector 63 (ChAd63) expressing CelTOS (Ad), a recombinant modified vaccinia virus Ankara expressing CelTOS (MVA), CelTOS conjugated to bacteriophage Qβ virus-like particles (VLPs), and a recombinant CelTOS protein expressed in eukaryotic HEK293T cells (protein). Inbred BALB/c mice and outbred CD-1 mice were immunized using the following prime-boost regimens: Ad-MVA, Ad-VLPs, and Ad-protein. Protective efficacy against sporozoite challenge was assessed after immunization using a novel chimeric rodent parasite (CelTOS). This chimeric parasite expresses CelTOS in place of the endogenous CelTOS and produces fully infectious sporozoites. A single Ad immunization in BALB/c and CD-1 mice induced anti-CelTOS antibodies which were boosted efficiently using MVA, VLP, or protein immunization. CelTOS-specific gamma interferon- and tumor necrosis factor alpha-producing CD8 T cells were induced at high frequencies by all prime-boost regimens in BALB/c mice but not in CD-1 mice; in CD-1 mice, they were only marginally increased after boosting with MVA. Despite the induction of anti-CelTOS antibodies and CelTOS-specific CD8 T-cell responses, only low levels of protective efficacy against challenge with CelTOS sporozoites were obtained using any immunization strategy. In BALB/c mice, no immunization regimens provided significant protection against a CelTOS chimeric sporozoite challenge. In CD-1 mice, modest protective efficacy against challenge with chimeric sporozoites expressing either CelTOS or CelTOS was observed using the Ad-protein vaccination regimen.
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