Determination of Specific Antibody Responses to the Six Species of Ebola and Marburg Viruses by Multiplexed Protein Microarrays

ABSTRACTInfectious hemorrhagic fevers caused by the Marburg and Ebola filoviruses result in human mortality rates of up to 90%, and there are no effective vaccines or therapeutics available for clinical use. The highly infectious and lethal nature of these viruses highlights the need for reliable and sensitive diagnostic methods. We assembled a protein microarray displaying nucleoprotein (NP), virion protein 40 (VP40), and glycoprotein (GP) antigens from isolates representing the six species of filoviruses for use as a surveillance and diagnostic platform. Using the microarrays, we examined serum antibody responses of rhesus macaques vaccinated with trivalent (GP, NP, and VP40) virus-like particles (VLP) prior to infection with the Marburg virus (MARV) (i.e.,Marburg marburgvirus) or the Zaire virus (ZEBOV) (i.e.,Zaire ebolavirus). The microarray-based assay detected a significant increase in antigen-specific IgG resulting from immunization, while a greater level of antibody responses resulted from challenge of the vaccinated animals with ZEBOV or MARV. Further, while antibody cross-reactivities were observed among NPs and VP40s of Ebola viruses, antibody recognition of GPs was very specific. The performance of mucin-like domain fragments of GP (GP mucin) expressed inEscherichia coliwas compared to that of GP ectodomains produced in eukaryotic cells. Based on results with ZEBOV and MARV proteins, antibody recognition of GP mucins that were deficient in posttranslational modifications was comparable to that of the eukaryotic cell-expressed GP ectodomains in assay performance. We conclude that the described protein microarray may translate into a sensitive assay for diagnosis and serological surveillance of infections caused by multiple species of filoviruses.

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Human Survivors of Disease Outbreaks Caused by Ebola or Marburg Virus Exhibit Cross-Reactive and Long-Lived Antibody Responses

Clinical and Vaccine Immunology ◽

10.1128/cvi.00107-16 ◽

2016 ◽

Vol 23 (8) ◽

pp. 717-724 ◽

Cited By ~ 30

Author(s):

Mohan Natesan ◽

Stig M. Jensen ◽

Sarah L. Keasey ◽

Teddy Kamata ◽

Ana I. Kuehne ◽

...

Keyword(s):

Immune Responses ◽

Protein Microarray ◽

Disease Outbreaks ◽

Cross Reactivity ◽

Marburg Virus ◽

Antibody Responses ◽

Diagnostic Methods ◽

Virus Infections ◽

Content Type ◽

Reactive Antibody

ABSTRACTA detailed understanding of serological immune responses to Ebola and Marburg virus infections will facilitate the development of effective diagnostic methods, therapeutics, and vaccines. We examined antibodies from Ebola or Marburg survivors 1 to 14 years after recovery from disease, by using a microarray that displayed recombinant nucleoprotein (NP), viral protein 40 (VP40), envelope glycoprotein (GP), and inactivated whole virions from six species of filoviruses. All three outbreak cohorts exhibited significant antibody responses to antigens from the original infecting species and a pattern of additional filoviruses that varied by outbreak. NP was the most cross-reactive antigen, while GP was the most specific. Antibodies from survivors of infections byMarburg marburgvirus(MARV) species were least cross-reactive, while those from survivors of infections bySudan virus(SUDV) species exhibited the highest cross-reactivity. Based on results revealed by the protein microarray, persistent levels of antibodies to GP, NP, and VP40 were maintained for up to 14 years after infection, and survival of infection caused by one species imparted cross-reactive antibody responses to other filoviruses.

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Antibody Recognition of the Dengue Virus Proteome and Implications for Development of Vaccines

Clinical and Vaccine Immunology ◽

10.1128/cvi.00016-11 ◽

2011 ◽

Vol 18 (4) ◽

pp. 523-532 ◽

Cited By ~ 14

Author(s):

Stefan Fernandez ◽

Emily D. Cisney ◽

Alexander P. Tikhonov ◽

Barry Schweitzer ◽

Robert J. Putnak ◽

...

Keyword(s):

Dengue Virus ◽

Vaccine Development ◽

Rhesus Macaques ◽

Protein Microarray ◽

Vaccination Strategy ◽

Antibody Responses ◽

Wild Type ◽

Antibody Recognition ◽

Immune Correlates ◽

The Tropics

ABSTRACTDengue is a mosquito-borne infection caused by four distinct serotypes of dengue virus, each appearing cyclically in the tropics and subtropics along the equator. Although vaccines are currently under development, none are available to the general population. One of the main impediments to the successful advancement of these vaccines is the lack of well-defined immune correlates of protection. Here, we describe a protein microarray approach for measuring antibody responses to the complete viral proteome comprised of the structural (capsid, membrane, and envelope) and nonstructural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) components of all four dengue virus serotypes (1 to 4). We examined rhesus macaques vaccinated with tetravalent vaccines consisting of live-attenuated virus (LAV) or purified inactivated virus (PIV), followed by boosting with LAV and challenging with wild-type dengue virus. We detected temporal increases in antibodies against envelope proteins in response to either vaccine, while only the PIV/LAV vaccination strategy resulted in anticapsid antibodies. In contrast to results from vaccination, naïve macaques challenged with wild-type viruses of each serotype demonstrated a balanced response to nonstructural and structural components, including responses against the membrane protein. Our results demonstrate discriminating details concerning the nature of antibody responses to dengue virus at the proteomic level and suggest the usefulness of this information for vaccine development.

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Rapid Detection of Serum Antibody by Dual-Path Platform VetTB Assay in White-Tailed Deer Infected with Mycobacterium bovis

Clinical and Vaccine Immunology ◽

10.1128/cvi.00120-13 ◽

2013 ◽

Vol 20 (6) ◽

pp. 907-911 ◽

Cited By ~ 18

Author(s):

Konstantin P. Lyashchenko ◽

Rena Greenwald ◽

Javan Esfandiari ◽

Daniel J. O'Brien ◽

Stephen M. Schmitt ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Mycobacterium Bovis ◽

Skin Testing ◽

Serum Antibody ◽

Antibody Responses ◽

Antibody Detection ◽

Serum Samples ◽

Content Type ◽

In The Wild ◽

Free Ranging

ABSTRACTBovine tuberculosis (TB) in cervids remains a significant problem affecting farmed herds and wild populations. Traditional skin testing has serious limitations in certain species, whereas emerging serological assays showed promising diagnostic performance. The recently developed immunochromatographic dual-path platform (DPP) VetTB assay has two antigen bands, T1 (MPB83 protein) and T2 (CFP10/ESAT-6 fusion protein), for antibody detection. We evaluated the diagnostic accuracy of this test by using serum samples collected from groups of white-tailed deer experimentally inoculated withMycobacterium bovis,M. aviumsubsp.paratuberculosis, orM. bovisBCG Pasteur. In addition, we used serum samples from farmed white-tailed deer in herds with no history of TB, as well as from free-ranging white-tailed deer culled during field surveillance studies performed in Michigan known to have bovine TB in the wild deer population. The DPP VetTB assay detected antibody responses in 58.1% of experimentally infected animals within 8 to 16 weeks postinoculation and in 71.9% of naturally infected deer, resulting in an estimated test sensitivity of 65.1% and a specificity of 97.8%. The higher seroreactivity found in deer with naturally acquiredM. bovisinfection was associated with an increased frequency of antibody responses to the ESAT-6 and CFP10 proteins, resulting in a greater contribution of these antigens, in addition to MPB83, to the detection of seropositive animals, compared with experimentalM. bovisinfection. Deer experimentally inoculated with eitherM. aviumsubsp.paratuberculosisorM. bovisBCG Pasteur did not produce cross-reactive antibodies that could be detected by the DPP VetTB assay. The present findings demonstrate the relatively high diagnostic accuracy of the DPP VetTB test for white-tailed deer, especially in the detection of naturally infected animals.

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Antibody Responses to a Spore Carbohydrate Antigen as a Marker of Nonfatal Inhalation Anthrax in Rhesus Macaques

Clinical and Vaccine Immunology ◽

10.1128/cvi.00475-10 ◽

2011 ◽

Vol 18 (5) ◽

pp. 743-748 ◽

Cited By ~ 12

Author(s):

Elke Saile ◽

Geert-Jan Boons ◽

Therese Buskas ◽

Russell W. Carlson ◽

Elmar L. Kannenberg ◽

...

Keyword(s):

Competitive Inhibition ◽

Rhesus Macaques ◽

Lethal Factor ◽

Structural Analog ◽

Diagnostic Value ◽

Carbohydrate Antigen ◽

Antibody Responses ◽

Content Type ◽

Aerosol Exposure ◽

Inhalation Anthrax

ABSTRACTTheBacillus anthracisexosporium protein BclA contains an O-linked antigenic tetrasaccharide whose terminal sugar is known as anthrose (J. M. Daubenspeck et al., J. Biol. Chem. 279:30945–30953, 2004). We hypothesized that serologic responses to anthrose may have diagnostic value in confirming exposure to aerosolizedB. anthracis. We evaluated the serologic responses to a synthetic anthrose-containing trisaccharide (ATS) in a group of five rhesus macaques that survived inhalation anthrax following exposure toB. anthracisAmes spores. Two of five animals (RM2 and RM3) were treated with ciprofloxacin starting at 48 hours postexposure and two (RM4 and RM5) at 72 h postexposure; one animal (RM1) was untreated. Infection was confirmed by blood culture and detection of anthrax toxin lethal factor (LF) in plasma. Anti-ATS IgG responses were determined at 14, 21, 28, and 35 days postexposure, with preexposure serum as a control. All animals, irrespective of ciprofloxacin treatment, mounted a specific, measurable anti-ATS IgG response. The earliest detectable responses were on days 14 (RM1, RM2, and RM5), 21 (RM4), and 28 (RM3). Specificity of the anti-ATS responses was demonstrated by competitive-inhibition enzyme immunoassay (CIEIA), in which a 2-fold (wt/wt) excess of carbohydrate in a bovine serum albumin (BSA) conjugate of the oligosaccharide (ATS-BSA) effected >94% inhibition, whereas a structural analog lacking the 3-hydroxy-3-methyl-butyryl moiety at the C-4" of the anthrosyl residue had no inhibition activity. These data suggest that anti-ATS antibody responses may be used to identify aerosol exposure toB. anthracisspores. The anti-ATS antibody responses were detectable during administration of ciprofloxacin.

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Serum Antibody Responses against Carbapenem-Resistant Klebsiella pneumoniae in Infected Patients

mSphere ◽

10.1128/msphere.01335-20 ◽

2021 ◽

Vol 6 (2) ◽

Author(s):

Kasturi Banerjee ◽

Michael P. Motley ◽

Elizabeth Diago-Navarro ◽

Bettina C. Fries

Keyword(s):

Klebsiella Pneumoniae ◽

Capsular Polysaccharide ◽

Serum Antibody ◽

Antibody Responses ◽

Capsular Polysaccharides ◽

Content Type ◽

Carbapenem Resistant ◽

Reactive Properties

ABSTRACT Capsular polysaccharide (CPS) heterogeneity within carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strain sequence type 258 (ST258) must be considered when developing CPS-based vaccines. Here, we sought to characterize CPS-specific antibody responses elicited by CR-Kp-infected patients. Plasma and bacterial isolates were collected from 33 hospital patients with positive CR-Kp cultures. Isolate capsules were typed by wzi sequencing. Reactivity and measures of efficacy of patient antibodies were studied against 3 prevalent CR-Kp CPS types (wzi29, wzi154, and wzi50). High IgG titers against wzi154 and wzi50 CPS were documented in 79% of infected patients. Patient-derived (PD) IgGs agglutinated CR-Kp and limited growth better than naive IgG and promoted phagocytosis of strains across the serotype isolated from their donors. Additionally, poly-IgG from wzi50 and wzi154 patients promoted phagocytosis of nonconcordant CR-Kp serotypes. Such effects were lost when poly-IgG was depleted of CPS-specific IgG. Additionally, mice infected with wzi50, wzi154, and wzi29 CR-Kp strains preopsonized with wzi50 patient-derived IgG exhibited lower lung CFU than controls. Depletion of wzi50 antibodies (Abs) reversed this effect in wzi50 and wzi154 infections, whereas wzi154 Ab depletion reduced poly-IgG efficacy against wzi29 CR-Kp. We are the first to report cross-reactive properties of CPS-specific Abs from CR-Kp patients through both in vitro and in vivo models. IMPORTANCE Carbapenem-resistant Klebsiella pneumoniae is a rapidly emerging public health threat that can cause fatal infections in up to 50% of affected patients. Due to its resistance to nearly all antimicrobials, development of alternate therapies like antibodies and vaccines is urgently needed. Capsular polysaccharides constitute important targets, as they are crucial for Klebsiella pneumoniae pathogenesis. Capsular polysaccharides are very diverse and, therefore, studying the host’s capsule-type specific antibodies is crucial to develop effective anti-CPS immunotherapies. In this study, we are the first to characterize humoral responses in infected patients against carbapenem-resistant Klebsiella pneumoniae expressing different wzi capsule types. This study is the first to report the efficacy of cross-reactive properties of CPS-specific Abs in both in vitro and in vivo models.

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Schistosoma mansoni Infection Impairs Antimalaria Treatment and Immune Responses of Rhesus Macaques Infected with Mosquito-Borne Plasmodium coatneyi

Infection and Immunity ◽

10.1128/iai.00590-12 ◽

2012 ◽

Vol 80 (11) ◽

pp. 3821-3827 ◽

Cited By ~ 16

Author(s):

Amma A. Semenya ◽

JoAnn S. Sullivan ◽

John W. Barnwell ◽

W. Evan Secor

Keyword(s):

Immune Responses ◽

Schistosoma Mansoni ◽

Malaria Infection ◽

Rhesus Macaques ◽

Antibody Responses ◽

Content Type ◽

Macaque Model ◽

Malaria Parasitemia ◽

Intravenous Inoculation ◽

Plasmodium Coatneyi

ABSTRACTMalaria and schistosomiasis are the world's two most important parasitic infections in terms of distribution, morbidity, and mortality. In areas wherePlasmodiumandSchistosomaspecies are both endemic, coinfections are commonplace. Mouse models demonstrate that schistosomiasis worsens a malaria infection; however, just as mice and humans differ greatly, the murine-infectingPlasmodiumspecies differ as much from those that infect humans. Research into human coinfections (Schistosoma haematobium-Plasmodium falciparumversusSchistosoma mansoni-P. falciparum) has produced conflicting results. The rhesus macaque model provides a helpful tool for understanding the role ofS. mansonion malaria parasitemia and antimalarial immune responses usingPlasmodium coatneyi, a malaria species that closely resemblesP. falciparuminfection in humans. Eight rhesus macaques were exposed toS. mansonicercariae. Eight weeks later, these animals plus 8 additional macaques were exposed to malaria either through bites of infected mosquitos or intravenous inoculation. When malaria infection was initiated from mosquito bites, coinfected animals displayed increased malaria parasitemia, decreased hematocrit levels, and suppressed malaria-specific antibody responses compared to those of malaria infection alone. However, macaques infected by intravenous inoculation with erythrocytic-stage parasites did not display these same differences in parasitemia, hematocrit, or antibody responses between the two groups. Use of the macaque model provides information that begins to unravel differences in pathological and immunological outcomes observed between humans withP. falciparumthat are coinfected withS. mansoniorS. haematobium. Our results suggest that migration of malaria parasites through livers harboring schistosome eggs may alter host immune responses and infection outcomes.

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Detection of Antibodies against Orientia tsutsugamushi Sca Proteins in Scrub Typhus Patients and Genetic Variation ofscaGenes of Different Strains

Clinical and Vaccine Immunology ◽

10.1128/cvi.00285-12 ◽

2012 ◽

Vol 19 (9) ◽

pp. 1442-1451 ◽

Cited By ~ 11

Author(s):

Na-Young Ha ◽

Yuri Kim ◽

Ji-Hye Choi ◽

Myung-Sik Choi ◽

Ik-Sang Kim ◽

...

Keyword(s):

Scrub Typhus ◽

Pcr Amplification ◽

Febrile Illness ◽

Immunofluorescence Assay ◽

Antibody Responses ◽

Diagnostic Methods ◽

Orientia Tsutsugamushi ◽

Content Type ◽

Asian Pacific Region ◽

Different Strains

ABSTRACTScrub typhus, caused byOrientia tsutsugamushiinfection, is one of the main causes of acute febrile illness in the Asian-Pacific region. Although early diagnosis and immediate antibiotic treatment are critical for reducing disease severity and mortality, current diagnostic methods using serological and molecular approaches have some limitations in sensitivity and applicability in clinical laboratories. In this study, we identified and characterizedO. tsutsugamushisurface cell antigen (sca) family genes encoding autotransporter proteins in order to test them as novel diagnostic targets. We evaluated antibody responses against the Sca proteins in scrub typhus patient sera and examined the genetic diversity of these genes in different strains after PCR amplification. Specific antibody responses against ScaA and ScaC were observed in patients with high indirect immunofluorescence assay titers (≥1:640), whereas specific responses against ScaB and ScaE were relatively low. Genetic analysis using genomic DNAs revealed thescagenes to be quite variable among the different strains. In contrast toscaA,scaC, andscaD, which were detected in all of the tested strains,scaBandscaEwere amplified differentially from the different strains, suggesting a differential presence of the genes in the genomes. Among the members of the gene family, the sequence ofscaCis the most highly conserved between the different strains, and the size ofscaDis the most variable due to the presence of different numbers of internal repeat sequences. These results suggest that thescagenes ofO. tsutsugamushimay be valuable targets for use in combination with classical assay methods for scrub typhus diagnosis.

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Refinement of a Human Challenge Model for Evaluation of Enterotoxigenic Escherichia coli Vaccines

Clinical and Vaccine Immunology ◽

10.1128/cvi.05194-11 ◽

2011 ◽

Vol 18 (10) ◽

pp. 1719-1727 ◽

Cited By ~ 56

Author(s):

Clayton Harro ◽

Subhra Chakraborty ◽

Andrea Feller ◽

Barbara DeNearing ◽

Alicia Cage ◽

...

Keyword(s):

Escherichia Coli ◽

Geometric Mean ◽

Serum Antibody ◽

Antibody Responses ◽

Enterotoxigenic Escherichia Coli ◽

Igg Antibody ◽

Content Type ◽

Heat Labile ◽

Serum Iga ◽

Average Maximum

ABSTRACTEnterotoxigenicEscherichia coli(ETEC) strain H10407 (serotype O78:H11 producing heat-labile toxin [LT], heat-stable toxin [ST], and colonization factor I [CFA/I]) induces reliably high diarrheal attack rates (ARs) in a human challenge model at doses of ≥109CFU. A descending-dose challenge study was conducted with changes to the standard fasting time and buffer formulation, seeking conditions that permit lower inocula while maintaining reproducibly high ARs. In cohort 1, 20 subjects were fasted overnight and randomized 1:1:1:1 to receive H10407 at doses of 108CFU with bicarbonate, 108CFU with CeraVacx, 107CFU with bicarbonate, or 107CFU with CeraVacx. Subsequent cohorts received H10407 (107CFU with bicarbonate) with similar fasting conditions. Cohort 2 included 15 ETEC-naïve volunteers. Cohort 3 included 10 ETEC-naïve volunteers and 10 rechallenged volunteers. In all, 25/35 (71%) ETEC-naïve recipients of 107CFU of H10407 developed moderate or severe diarrhea (average maximum stool output/24 h = 1,042 g), and most (97%) shed H10407 (maximum geometric mean titer = 7.5 × 107CFU/gram of stool). Only one of 10 rechallenged volunteers developed diarrhea. These rechallenged subjects had reduced intestinal colonization, reflected by quantitative microbiology of fecal samples. Among the 35 ETEC-naïve subjects, anti-lipopolysaccharide (LPS) O78 serum antibody responses were striking, with positive IgA and IgG antibody responses in 33/35 (94%) and 25/35 (71%), respectively. Anti-heat-labile enterotoxin (LTB) serum IgA and IgG responses developed in 19/35 (54%) and 14/35 (40%) subjects, respectively. Anti-CFA/I serum IgA and IgG responses were detected in 15/35 (43%) and 8/35 (23%) subjects. After the second challenge, participants exhibited blunted anti-LPS and -LTB responses but a booster response to CFA/I. This ETEC model should prove useful in the future evaluation of ETEC vaccine candidates.

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Diversity of Antibody Responses to Borrelia burgdorferi in Experimentally Infected Beagle Dogs

Clinical and Vaccine Immunology ◽

10.1128/cvi.00018-14 ◽

2014 ◽

Vol 21 (6) ◽

pp. 838-846 ◽

Cited By ~ 9

Author(s):

Elisabeth Baum ◽

Deborah A. Grosenbaugh ◽

Alan G. Barbour

Keyword(s):

Borrelia Burgdorferi ◽

Binding Protein ◽

Protein Microarray ◽

Antibody Responses ◽

Domestic Dog ◽

Beagle Dogs ◽

Effective Population ◽

Content Type ◽

Immunogenic Proteins ◽

Antibody Levels

ABSTRACTLyme borreliosis (LB) is a common infection of domestic dogs in areas where there is enzootic transmission of the agentBorrelia burgdorferi. While immunoassays based on individual subunits have mostly supplanted the use of whole-cell preparations for canine serology, only a limited number of informative antigens have been identified. To more broadly characterize the antibody responses toB. burgdorferiinfection and to assess the diversity of those responses in individual dogs, we examined sera from 32 adult colony-bred beagle dogs that had been experimentally infected withB. burgdorferithrough tick bites and compared those sera in a protein microarray with sera from uninfected dogs in their antibody reactivities to various recombinant chromosome- and plasmid-encodedB. burgdorferiproteins, including 24 serotype-defining OspC proteins of North America. The profiles of immunogenic proteins for the dogs were largely similar to those for humans and natural-reservoir rodents; these proteins included the decorin-binding protein DbpB, BBA36, BBA57, BBA64, the fibronectin-binding protein BBK32, VlsE, FlaB and other flagellar structural proteins, Erp proteins, Bdr proteins, and all of the OspC proteins. In addition, the canine sera bound to the presumptive lipoproteins BBB14 and BB0844, which infrequently elicited antibodies in humans or rodents. Although the beagle, like most other domestic dog breeds, has a small effective population size and features extensive linkage disequilibrium, the group of animals studied here demonstrated diversity in antibody responses in measures of antibody levels and specificities for conserved proteins, such as DbpB, and polymorphic proteins, such as OspC.

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3M-052, a synthetic TLR-7/8 agonist, induces durable HIV-1 envelope–specific plasma cells and humoral immunity in nonhuman primates

Science Immunology ◽

10.1126/sciimmunol.abb1025 ◽

2020 ◽

Vol 5 (48) ◽

pp. eabb1025 ◽

Cited By ~ 4

Author(s):

Sudhir Pai Kasturi ◽

Mohammed Ata Ur Rasheed ◽

Colin Havenar-Daughton ◽

Mathew Pham ◽

Traci Legere ◽

...

Keyword(s):

Plasma Cells ◽

Rhesus Macaques ◽

Serum Antibody ◽

Plga Nanoparticles ◽

Antibody Responses ◽

Blood Monocytes ◽

Follicular Helper ◽

Clade C ◽

Hiv 1 ◽

Induce Antibody

A fundamental challenge in vaccinology is learning how to induce durable antibody responses. Live viral vaccines induce antibody responses that last a lifetime, but those induced with subunit vaccines wane rapidly. Studies in mice and humans have established that long-lived plasma cells (LLPCs) in the bone marrow (BM) are critical mediators of durable antibody responses. Here, we present data that adjuvanting an HIV-1 clade C 1086.C–derived gp140 immunogen (Env) with a novel synthetic Toll-like receptor (TLR)–7/8 agonist named 3M-052 formulated in poly(lactic-co-glycolic)acid or PLGA nanoparticles (NPs) or with alum, either alone or in combination with a TLR-4 agonist GLA, induces notably high and persistent (up to ~1 year) frequencies of Env-specific LLPCs in the BM and serum antibody responses in rhesus macaques. Up to 36 and 18% of Env-specific cells among total IgG-secreting BM-resident plasma cells were detected at peak and termination, respectively. In contrast, adjuvanting Env with alum or GLA in NP induced significantly lower (~<100-fold) LLPC and antibody responses. Immune responses induced by 3M-052 were also significantly higher than those induced by a combination of TLR-7/8 (R848) and TLR-4 (MPL) agonists. Adjuvanting Env with 3M-052 also induced robust activation of blood monocytes, strong plasmablast responses in blood, germinal center B cells, T follicular helper (TFH) cells, and persistent Env-specific plasma cells in draining lymph nodes. Overall, these results demonstrate efficacy of 3M-052 in promoting high magnitude and durability of antibody responses via robust stimulation of innate immunity and BM-resident LLPCs.

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