scholarly journals A lymph node–targeted Amphiphile vaccine induces potent cellular and humoral immunity to SARS-CoV-2

2021 ◽  
Vol 7 (6) ◽  
pp. eabe5819
Author(s):  
Martin P. Steinbuck ◽  
Lochana M. Seenappa ◽  
Aniela Jakubowski ◽  
Lisa K. McNeil ◽  
Christopher M. Haqq ◽  
...  
Keyword(s):  
Immune Responses ◽  
Receptor Binding ◽  
Lung Parenchyma ◽  
Antibody Responses ◽  
Protein Subunit ◽  
T Helper 1 ◽  
Humoral Immune ◽  
Adaptive Immune ◽  
Humoral Immune Responses ◽  
Cellular And Humoral Immunity

The profound consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mandate urgent development of effective vaccines. Here, we evaluated an Amphiphile (AMP) vaccine adjuvant, AMP-CpG, composed of diacyl lipid–modified CpG, admixed with the SARS-CoV-2 Spike-2 receptor binding domain protein as a candidate vaccine (ELI-005) in mice. AMP modification efficiently delivers CpG to lymph nodes, where innate and adaptive immune responses are generated. Compared to alum, immunization with AMP-CpG induced >25-fold higher antigen-specific T cells that produced multiple T helper 1 (TH1) cytokines and trafficked into lung parenchyma. Antibody responses favored TH1 isotypes (IgG2c and IgG3) and potently neutralized Spike-2-ACE2 receptor binding, with titers 265-fold higher than natural convalescent patient COVID-19 responses; T cell and antibody responses were maintained despite 10-fold dose reduction in Spike antigen. Both cellular and humoral immune responses were preserved in aged mice. These advantages merit clinical translation to SARS-CoV-2 and other protein subunit vaccines.

scholarly journals A Lymph Node Targeted Amphiphile Vaccine Induces Potent Cellular and Humoral Immunity to SARS-CoV-2

2020 ◽  
Author(s):  
Martin P. Steinbuck ◽  
Lochana M. Seenappa ◽  
Aniela Jakubowski ◽  
Lisa K. McNeil ◽  
Christopher M. Haqq ◽  
...  
Keyword(s):  
Immune Responses ◽  
Receptor Binding ◽  
Lung Parenchyma ◽  
Social Consequences ◽  
Protein Subunit ◽  
Humoral Immune ◽  
Adaptive Immune ◽  
Humoral Immune Responses ◽  
Cellular And Humoral Immunity ◽  
Th1 Cytokines

AbstractThe SARS-CoV-2 pandemic has led to public health, economic, and social consequences that mandate urgent development of effective vaccines to contain or eradicate infection. To that end, we evaluated a novel amphiphile (AMP) vaccine adjuvant, AMP-CpG, composed of diacyl lipid-modified CpG, admixed with the SARS-CoV-2 Spike-2 receptor binding domain protein as a candidate vaccine (ELI-005) in mice. AMP immunogens are efficiently delivered to lymph nodes, where innate and adaptive immune responses are generated. Compared to alum, AMP immunization induced >25-fold higher antigen-specific T cells which produced multiple Th1 cytokines and trafficked into lung parenchyma and respiratory secretions. Antibody responses favored Th1 isotypes (IgG2bc, IgG3) and potently neutralized Spike-2-ACE2 receptor binding, with titers 265-fold higher than the natural immune response from convalescent COVID-19 patients; responses were maintained despite 10-fold dose-reduction in Spike antigen. Both cellular and humoral immune responses were preserved in aged mice. These advantages merit clinical translation to SARS-CoV-2 and other protein subunit vaccines.

scholarly journals mRNA vaccination in people over 80 years of age induces strong humoral immune responses against SARS-CoV-2 with cross neutralization of P.1 Brazilian variant

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Helen Parry ◽  
Gokhan Tut ◽  
Rachel Bruton ◽  
Sian Faustini ◽  
Christine Stephens ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cellular Response ◽  
Humoral Response ◽  
Antibody Responses ◽  
Vaccine Platform ◽  
Humoral Immune ◽  
Vaccine Responses ◽  
Cellular Immune Responses ◽  
Humoral Immune Responses ◽  
Cellular Immune

Age is the major risk factor for mortality after SARS-CoV-2 infection and older people have received priority consideration for COVID-19 vaccination. However, vaccine responses are often suboptimal in this age group and few people over the age of 80 years were included in vaccine registration trials. We determined the serological and cellular response to spike protein in 100 people aged 80–96 years at 2 weeks after the second vaccination with the Pfizer BNT162b2 mRNA vaccine. Antibody responses were seen in every donor with high titers in 98%. Spike-specific cellular immune responses were detectable in only 63% and correlated with humoral response. Previous SARS-CoV-2 infection substantially increased antibody responses after one vaccine and antibody and cellular responses remained 28-fold and 3-fold higher, respectively, after dual vaccination. Post-vaccine sera mediated strong neutralization of live Victoria infection and although neutralization titers were reduced 14-fold against the P.1 variant first discovered in Brazil they remained largely effective. These data demonstrate that the mRNA vaccine platform delivers strong humoral immunity in people up to 96 years of age and retains broad efficacy against the P.1 variant of concern.

scholarly journals Structure-Based Stabilization of HIV-1 gp120 Enhances Humoral Immune Responses to the Induced Co-Receptor Binding Site

2009 ◽  
Vol 5 (5) ◽  
pp. e1000445 ◽  
Author(s):  
Barna Dey ◽  
Krisha Svehla ◽  
Ling Xu ◽  
Dianne Wycuff ◽  
Tongqing Zhou ◽  
...  
Keyword(s):  
Immune Responses ◽  
Binding Site ◽  
Receptor Binding ◽  
Receptor Binding Site ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Hiv 1

scholarly journals Chimeric Plant Virus Particles Administered Nasally or Orally Induce Systemic and Mucosal Immune Responses in Mice

1999 ◽  
Vol 73 (2) ◽  
pp. 930-938 ◽  
Author(s):  
Frank R. Brennan ◽  
Trevor Bellaby ◽  
Sharon M. Helliwell ◽  
Tim D. Jones ◽  
Søren Kamstrup ◽  
...  
Keyword(s):  
Immune Responses ◽  
Plant Virus ◽  
Oral Immunization ◽  
Plant Viruses ◽  
T Helper 1 ◽  
Virus Particles ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Recombinant Plant ◽  
Chimeric Plant

ABSTRACT The humoral immune responses to the D2 peptide of fibronectin-binding protein B (FnBP) of Staphylococcus aureus, expressed on the plant virus cowpea mosaic virus (CPMV), were evaluated after mucosal delivery to mice. Intranasal immunization of these chimeric virus particles (CVPs), either alone or in the presence of ISCOM matrix, primed CPMV-specific T cells and generated high titers of CPMV- and FnBP-specific immunoglobulin G (IgG) in sera. Furthermore, CPMV- and FnBP-specific IgA and IgG could also be detected in the bronchial, intestinal, and vaginal lavage fluids, highlighting the ability of CVPs to generate antibody at distant mucosal sites. IgG2a and IgG2b were the dominant IgG subclasses in sera to both CPMV and FnBP, demonstrating a bias in the response toward the T helper 1 type. The sera completely inhibited the binding of human fibronectin to the S. aureus FnBP. Oral immunization of the CVPs also generated CPMV- and FnBP-specific serum IgG; however, these titers were significantly lower and more variable than those generated by the intranasal route, and FnBP-specific intestinal IgA was undetectable. Neither the ISCOM matrix nor cholera toxin enhanced these responses. These studies demonstrate for the first time that recombinant plant viruses have potential as mucosal vaccines without the requirement for adjuvant and that the nasal route is most effective for the delivery of these nonreplicating particles.

scholarly journals Limited Local and Systemic Antibody Responses toNeisseria gonorrhoeae during Uncomplicated Genital Infections

1999 ◽  
Vol 67 (8) ◽  
pp. 3937-3946 ◽  
Author(s):  
Spencer R. Hedges ◽  
Matthew S. Mayo ◽  
Jiri Mestecky ◽  
Edward W. Hook ◽  
Michael W. Russell
Keyword(s):  
Immune Responses ◽  
Transmitted Disease ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Genital Infections ◽  
Sexually Transmitted ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Repeated Infections ◽  
Antibody Levels

ABSTRACT Repeated infections with Neisseria gonorrhoeae are common among patients attending sexually transmitted disease clinics. We examined whether previous infections or site of infection altered the local and systemic antigonococcal antibody levels in males and females. Antibodies against N. gonorrhoeae MS11 and the patients’ homologous infecting isolates were measured by enzyme-linked immunosorbent assay. In general, the local and systemic immune responses to gonococci were extremely modest. There was a slight increase in serum immunoglobulin G (IgG) against the MS11 strain and the homologous isolates in infected males. Levels of serum IgA1 antibodies against MS11 were slightly higher in infected than in uninfected females. A history of previous infections with N. gonorrhoeae did not alter the antibody levels in patients with a current infection, suggesting that immunological memory is not induced by uncomplicated gonococcal infections. Antibody responses to infected subjects’ homologous isolates were observed in cervical mucus; IgA1 levels increased while IgG levels decreased. The decline in mucosal IgG against the homologous isolates was less common in subjects having both rectal and cervical infections; otherwise, no effect of rectal involvement was observed. The absence of substantially higher antibody levels to gonococci where there is infection at a site known to contain organized lymphoid tissue suggests that the low levels of responses to uncomplicated infections may not be due simply to an absence of inductive sites in the genital tract. We propose that in addition to its potential ability to avoid the effects of an immune response,N. gonorrhoeae does not elicit strong humoral immune responses during uncomplicated genital infections.

Regulation of humoral immunity in rats by pituitary hormones

1981 ◽  
Vol 98 (4) ◽  
pp. 506-513 ◽  
Author(s):  
Istvan Berczi ◽  
Eva Nagy ◽  
Kalman Kovacs ◽  
Eva Horvath
Keyword(s):  
Immune Responses ◽  
Antibody Formation ◽  
Pituitary Hormones ◽  
Antibody Responses ◽  
Igg Antibodies ◽  
E Coli ◽  
Humoral Immune ◽  
Fischer 344 ◽  
Humoral Immune Responses ◽  
Hypophysectomized Rats

Abstract. Hypophysectomized female Fischer 344 and Wistar-Furth rats had severely impaired primary and secondary antibody responses to sheep red blood cells (SRBC). Mercaptoethanol-sensitive (IgM) and mercaptoethanol-resistant (IgG) antibodies were similarly affected. Titers to E. Coli 055:B5 lipopolysaccharide were also significantly decreased in such animals. The antibody response of hypophysectomized rats could be restored by syngeneic pituitary grafts when placed under the kidney capsule or by prolactin treatment. Growth hormone was less effective in this respect than prolactin. Treatment of normal rats with ACTH suppressed their antibody formation to SRBC. These results indicate that the pituitary gland has the potential to regulate humoral immune responses.

scholarly journals Cellular and Humoral Immune Responses toBorrelia burgdorferi Antigens in Patients with Culture-Positive Early Lyme Disease

2001 ◽  
Vol 69 (12) ◽  
pp. 7437-7444 ◽  
Author(s):  
Austin Vaz ◽  
Lisa Glickstein ◽  
Jodie A. Field ◽  
Gail McHugh ◽  
Vijay K. Sikand ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Immune Responses ◽  
Erythema Migrans ◽  
Antibody Responses ◽  
Humoral Immune ◽  
Convalescent Phase ◽  
Humoral Immune Responses ◽  
Antibody Reactivity ◽  
Disseminated Disease ◽  
Culture Positive

ABSTRACT We determined cellular and humoral immune responses toBorrelia burgdorferi lysate and to recombinant flagellin (FlaB), OspC, and OspA in acute- and convalescent-phase samples from 39 culture-positive patients with erythema migrans and in 20 healthy control subjects. During the acute illness, a median of 4 days after the onset of erythema migrans, 51% of the patients had proliferative cellular responses and 72% had antibody responses to at least one of the borrelial antigens tested. During convalescence, at the conclusion of antibiotic therapy, 64% of the patients had proliferative cellular reactivity and 95% had antibody reactivity with at least one of the spirochetal antigens tested. In both acute- and convalescent-phase samples, cellular immune responses were found as frequently to OspA as to OspC and FlaB. Although antibody responses were also frequently seen to OspC and FlaB, only a few patients had marginal antibody reactivity with OspA. The percentage of patients with proliferative responses was similar in those with clinical evidence of localized or disseminated infection, whereas humoral reactivity was found more often in those with disseminated disease. We conclude that cellular and humoral responses to B. burgdorferi antigens are often found among patients with early Lyme disease. In contrast with the other antigens tested, cellular but not humoral reactivity was often found with OspA.

scholarly journals Replication-Defective Adenovirus Serotype 5 Vectors Elicit Durable Cellular and Humoral Immune Responses in Nonhuman Primates

2005 ◽  
Vol 79 (10) ◽  
pp. 6516-6522 ◽  
Author(s):  
Sampa Santra ◽  
Michael S. Seaman ◽  
Ling Xu ◽  
Dan H. Barouch ◽  
Carol I. Lord ◽  
...  
Keyword(s):  
Immune Responses ◽  
Adenovirus Serotype ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Monkey Model ◽  
Immunodeficiency Virus ◽  
Serotype 5 ◽  
Rapid Generation ◽  
Cellular And Humoral Immunity ◽  
Replication Defective Adenovirus

ABSTRACT The magnitude and durability of immune responses induced by replication-defective adenovirus serotype 5 (ADV5) vector-based vaccines were evaluated in the simian-human immunodeficiency virus/rhesus monkey model. A single inoculation of recombinant ADV5 vector constructs induced cellular and humoral immunity, but the rapid generation of neutralizing anti-Ad5 antibodies limited the immunity induced by repeated vector administration. The magnitude and durability of the immune responses elicited by these vaccines were greater when they were delivered as boosting immunogens in plasmid DNA-primed monkeys than when they were used as single-modality immunogens. Therefore, administration of ADV5-based vectors in DNA-primed subjects may be a preferred use of this vaccine modality for generating long-term immune protection.

scholarly journals Antigen targeting to dendritic cells elicits long-lived T cell help for antibody responses

2006 ◽  
Vol 203 (3) ◽  
pp. 599-606 ◽  
Author(s):  
Silvia B. Boscardin ◽  
Julius C.R. Hafalla ◽  
Revati F. Masilamani ◽  
Alice O. Kamphorst ◽  
Henry A. Zebroski ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Immune Responses ◽  
Lymphoid Organs ◽  
Antibody Responses ◽  
Carrier Protein ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Maturation Stimulus ◽  
T Cell Help

Resistance to several prevalent infectious diseases requires both cellular and humoral immune responses. T cell immunity is initiated by mature dendritic cells (DCs) in lymphoid organs, whereas humoral responses to most antigens require further collaboration between primed, antigen-specific helper T cells and naive or memory B cells. To determine whether antigens delivered to DCs in lymphoid organs induce T cell help for antibody responses, we targeted a carrier protein, ovalbumin (OVA), to DCs in the presence of a maturation stimulus and assayed for antibodies to a hapten, (4-hydroxy-3-nitrophenyl) acetyl (NP), after boosting with OVA-NP. A single DC-targeted immunization elicited long-lived T cell helper responses to the carrier protein, leading to large numbers of antibody-secreting cells and high titers of high-affinity antihapten immunoglobulin Gs. Small doses of DC-targeted OVA induced higher titers and a broader spectrum of anti-NP antibody isotypes than large doses of OVA in alum adjuvant. Similar results were obtained when the circumsporozoite protein of Plasmodium yoelii was delivered to DCs. We conclude that antigen targeting to DCs combined with a maturation stimulus produces broad-based and long-lived T cell help for humoral immune responses.

Sign in / Sign up

Export Citation Format

Share Document