The Effect of Adjuvants of Different Groups on the Immunogenicity of Vaccines against Hemorrhagic Fever with Renal Syndrome

Effects of different classes of adjuvants (aluminum hydroxide, spherical protein particles, thermolabile В protein, low-endotoxic pyrogen-free lipopolysaccharide) have been studied in order to enhance the immunogenicity of inactivated vaccines against hemorrhagic fever with renal syndrome. The Puumala virus-based monovaccine and multivalent vaccine based on Puumala, Hantaan and Sochi viruses were analyzed, and BALB/c mice were used as an animal model. It was shown that low-endotoxic pyrogen-free lipopolysaccharide stimulated the production of virus-neutralizing antibodies and increased the vaccine stability during storage, which allows to reduce the antigenic load of the vaccine. Aluminum hydroxide slightly increased the production of T-cells immune response mediators and did not affect the neutralizing antibodies induction and vaccine stability. Despite the adjuvant effect, it was shown that spherical protein particles and thermolabile В protein were unacceptable for vaccines administered to humans due to the high protein load and toxic effects, respectively. hantavirases, hemorrhagic fever with renal syndrome, inactivated vaccines, adjuvants, immune response The authors are grateful to Dr. O.V. Karpova (Department of Virology, Moscow State University) for providing the preparation of spherical particles, and to Dr. A.N. Noskov (Gamaleya Research Institute of Epidemiology and Microbiology, Moscow) for providing the preparation of the thermolabile enterotoxin B-subunit.

Download Full-text

EFEITO ADJUVANTE DO CLORETO DE DIMETILDIOCTADECILAMÔNIO EM PREPARAÇÕES DE TOXÓIDE TETÂNICO

Archives of Veterinary Science ◽

10.5380/avs.v8i1.4019 ◽

2003 ◽

Vol 8 (1) ◽

Cited By ~ 1

Author(s):

L.C. SILVA ◽

E. TAKIUCHI ◽

A.F. ALFIERI ◽

A.A. ALFIERI

Keyword(s):

Immune Response ◽

Ammonium Chloride ◽

Aluminum Hydroxide ◽

Guinea Pigs ◽

Neutralizing Antibodies ◽

Immune Cell ◽

Delayed Type Hypersensitivity ◽

Cell Immune Response ◽

Adjuvant Effect ◽

Group B

Foram formuladas duas vacinas contendo a mesma concentração de toxina, com o intuito de se avaliar a habilidade do adjuvante cloreto de demetiloctadecilamônio (DDA cloreto) em potencializar a resposta imune em cobaias imunizada com o toxóide tetânico. A vacina A foi adsorvida com hidróxido de alumínio e a vacina B cmpreendia a associação do hidróxido de alumínio e DDA cloreto. Os títulos de antitoxina no soro dos cobaios imunizados foram quantificados por soroneutralização em camundongos frente a uma dose contendo 1 Lp/10 (limite paralítico) de toxina tetânica. A inclusão do DDA cloreto em vacinas constituídas por toxóide tetânico adsorvido com hidróxido de alumínio promoveu maior ativação das respostas imunes humoral e celular de cobaios, quando comparada à resposta imune dos animais que receberam o antígeno adsorvido apenas com o hidróxido de alumínio. Os animais recebedores da vacina B apresentaram títulos de anticorpos neutralizantes 2,66 vezes maiores que os que recebedores a vacina A, demonstrando a potencialização da resposta imune humoral promovida pelo DDA cloreto. A resposta imune celular, avaliada pela reação de hipersensibilidade cutânea tardia, foi 17,8 maior no grupo B. Esses resultados demonstram que o DDA cloreto é um potente ativador da resposta imune humoral e celular de cobaios imunizados com o toxóide tetânico. Adjuvant effect of dimethyl dioctadecyl ammonium chloride in tetanic toxoid preparations Abstract Two vaccines were formulated with the same concentration of antigen and different adjuvants to assess the performance of dimethyl dioctadecyl ammonium chloride (DDA chloride) in boosting the immune response in guinea pigs immunized with tetanic toxoid. Vaccine A was adsorbed with aluminum hydroxide and vaccine B contained an association of aluminum hydroxide and DDA chloride. The antitoxin titres in the immunized guinea pig sera were assessed serum neutralization in mice using a toxin containing one Lp/10 dose (paralytic limit). The inclusion of DDA chloride in vaccines made up of tetanic toxoid adsorbed with aluminum hydroxide causes a greater activation of the humoral and cell immune response in guinea pigs when compared with the animals which received the antigen adsorbed only with aluminum hydroxide. The animals which received vaccine B had 2.66 times more neutralizing antibodies than those which received vaccine A, showing the boosting of the humoral immune response caused by DDA chloride. The animals from group B also had a strong immune cell response by the delayed type hypersensitivity reaction, which was 17.8 times higher than group A. These results show that DDA chloride is a potent activator of the humoral and cell immune response in guinea pigs immunized with tetanic toxoid.

Download Full-text

Pre-Existing Anti-GM-CSF Autoantibodies in Patients with AML, CML and MDS Are Associated with Compromised Immune Response to PR1 Peptide Vaccination.

Blood ◽

10.1182/blood.v106.11.3257.3257 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3257-3257

Author(s):

Anna Sergeeva ◽

Eric Wieder ◽

Nancy Milam ◽

Yoko Ono ◽

Rosa Rios ◽

...

Keyword(s):

Immune Response ◽

Clinical Response ◽

Myeloid Leukemia ◽

Neutralizing Antibodies ◽

Neutralization Assay ◽

Adjuvant Effect ◽

Lymphoid Leukemia ◽

Gm Csf ◽

Amino Acid Peptide ◽

Clinical Responses

Abstract Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (rhGM-CSF) is used as an adjuvant in tumor vaccination to boost the immune response by causing outgrowth and maturation of dendritic cells. Autoantibodies to GM-CSF that block its activity have been described in patients with alveolar proteinosis, and administration of pharmacological doses of rhGM-CSF might result in the induction of anti-GM-CSF antibodies, especially when rhGM-CSF is injected with other adjuvants. Our laboratory has identified PR1, an HLA-A2-restricted 9 amino acid peptide derived from proteinase 3, as a leukemia-associated antigen for leukemia-reactive cytotoxic T lymphocytes (CTL). In a phase I/II clinical trial, patients with myeloid leukemia received PR1 peptide as a subcutaneous vaccine in incomplete Freund’s adjuvant (IFA) with a subsequent injection of 75mg rhGM-CSF every 3 weeks for 3 total injections. Immune response to vaccine was evaluated by PR1/HLA-A2 tetramer staining and clinical response was evaluated by NCI criteria, as have been reported previously (ASH, 2004). We sought to determine whether the PR1 vaccine induced GM-CSF-neutralizing antibodies, based on the hypothesis that such antibodies may compromise the adjuvant effect. Using ELISA, Western blot and a TF-1 cells-based GM-CSF neutralization assay, we tested 9 AML, 5 MDS and 5 CML patients that received PR1 vaccine for anti-GM-CSF antibodies. We identified anti-GM-CSF IgG in 6 out of 19 (32%) patients (53±17RU/ml) compared to none out of 33 (6±2RU/ml) healthy donors (p=0.008). Additionally we detected anti-GM-CSF IgM and IgA in 5 (33%) and 3 (20%) out of 15 patients, respectively. To our surprise, anti-GM-CSF IgG, IgA and IgM titers did not increase after vaccination (p=0.18; N=17) suggesting that the antibodies were present before treatment. Moreover, pre-existing anti-GM-CSF IgG titers were higher (113±40RU/ml; n=8) in patients that did not have immune response after vaccine than in immune responders (37±26.1RU/ml; n=8)(p=0.05). Furthermore, none of six patients with higher anti-GM-CSF IgG had clinical remission after vaccination. In contrast, 6 out of 11 patients (54%) with lower anti-GM-CSF IgG had clinical response to vaccination (p=0.02). Additional analysis of 16 AML, 17 CML, 2 ALL and 4 CLL patients showed that anti-GM-CSF IgG were present only in patients with myeloid leukemia, compared to patients in remission (p=0.001) or those with lymphoid leukemia (p=0.001). Only sera from one patient studied showed neutralizing activity. Anti-GM-CSF IgG titers did not correlate with GM-CSF expression in peripheral blood cells (mRNA transcripts) or serum (protein), which were not different from healthy controls. Our data show that vaccination with PR1 peptide did not induce anti-GM-CSF antibodies. However, pre-existing autoantibodies were associated with lower rates of immune and clinical responses suggesting that anti-GM-CSF antibodies might compromise effective vaccination. As reported elsewhere, immune and clinical responses to PR1 vaccination correlate inversely with disease burden before vaccination. Here we demonstrate the association of anti-GM-CSF antibodies and presence of disease. Since anti-GM-CSF antibodies were mostly non-neutralizing we have not established physiological relevance of these autoantibodies. Nevertheless, this association needs to be explored further since this is also the first report of naturally occurring IgA and IgM anti-GM-CSF autoantibodies.

Download Full-text

Immunization with DNA Plasmids Coding for Crimean-Congo Hemorrhagic Fever Virus Capsid and Envelope Proteins and/or Virus-Like Particles Induces Protection and Survival in Challenged Mice

Journal of Virology ◽

10.1128/jvi.02076-16 ◽

2017 ◽

Vol 91 (10) ◽

Cited By ~ 28

Author(s):

Jorma Hinkula ◽

Stéphanie Devignot ◽

Sara Åkerström ◽

Helen Karlberg ◽

Eva Wattrang ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Dna Vaccine ◽

Neutralizing Antibodies ◽

Hemorrhagic Fever ◽

Fever Virus ◽

Vaccine Candidates ◽

Th1 Response ◽

Crimean Congo Hemorrhagic Fever ◽

Hemorrhagic Fever Virus

ABSTRACT Crimean-Congo hemorrhagic fever virus (CCHFV) is a bunyavirus causing severe hemorrhagic fever disease in humans, with high mortality rates. The requirement of a high-containment laboratory and the lack of an animal model hampered the study of the immune response and protection of vaccine candidates. Using the recently developed interferon alpha receptor knockout (IFNAR−/−) mouse model, which replicates human disease, we investigated the immunogenicity and protection of two novel CCHFV vaccine candidates: a DNA vaccine encoding a ubiquitin-linked version of CCHFV Gc, Gn, and N and one using transcriptionally competent virus-like particles (tc-VLPs). In contrast to most studies that focus on neutralizing antibodies, we measured both humoral and cellular immune responses. We demonstrated a clear and 100% efficient preventive immunity against lethal CCHFV challenge with the DNA vaccine. Interestingly, there was no correlation with the neutralizing antibody titers alone, which were higher in the tc-VLP-vaccinated mice. However, the animals with a lower neutralizing titer, but a dominant cell-mediated Th1 response and a balanced Th2 response, resisted the CCHFV challenge. Moreover, we found that in challenged mice with a Th1 response (immunized by DNA/DNA and boosted by tc-VLPs), the immune response changed to Th2 at day 9 postchallenge. In addition, we were able to identify new linear B-cell epitope regions that are highly conserved between CCHFV strains. Altogether, our results suggest that a predominantly Th1-type immune response provides the most efficient protective immunity against CCHFV challenge. However, we cannot exclude the importance of the neutralizing antibodies as the surviving immunized mice exhibited substantial amounts of them. IMPORTANCE Crimean-Congo hemorrhagic fever virus (CCHFV) is responsible for hemorrhagic diseases in humans, with a high mortality rate. There is no FDA-approved vaccine, and there are still gaps in our knowledge of the immune responses to infection. The recently developed mouse models mimic human CCHF disease and are useful to study the immunogenicity and the protection by vaccine candidates. Our study shows that mice vaccinated with a specific DNA vaccine were fully protected. Importantly, we show that neutralizing antibodies are not sufficient for protection against CCHFV challenge but that an extra Th1-specific cellular response is required. Moreover, we describe the identification of five conserved B-cell epitopes, of which only one was previously known, that could be of great importance for the development of diagnostics tools and the improvement of vaccine candidates.

Download Full-text

Immunological Analysis of People in Northeast China after SARS-COV-2 Inactivated Vaccine Injection

Vaccines ◽

10.3390/vaccines9091028 ◽

2021 ◽

Vol 9 (9) ◽

pp. 1028

Author(s):

Yu Fu ◽

Fang Chen ◽

Lifen Cui ◽

Yue Zhao ◽

Henan Zhang ◽

...

Keyword(s):

Immune Response ◽

Cellular Immunity ◽

Neutralizing Antibodies ◽

Lymphocyte Subsets ◽

Statistical Significance ◽

Neutralizing Antibody ◽

Upward Trend ◽

Hla Dr ◽

Inactivated Vaccines ◽

Type Response

Clarifying changes in the immune microenvironment caused by vaccination is crucial for the development and application of vaccines. In this study, we analyzed seroconversion of antibodies, 12 key cytokines, and 34 lymphocyte subsets at three time points (D-1, D14, and D42) around vaccination and differences between two inactivated vaccines (Sinopharm and Sinovas) to understand the immune response induced by inactivated vaccines in the real world. The results showed that 62.5% and 75% of the participants achieved neutralizing antibody seroconversion on D14 and D42, respectively. After vaccination, IL-5 and IL-6 increased, and INF-γ decreased. IL6, IL-1B, INF-γ, IL-8, and IL-12p70 showed statistical significance in the comparison of different groups. In terms of lymphocyte subsets, CD3 +, CD56 +, CD3 + CD8 +, CD8 + CD71 +, and CD56 + CD71 + showed upward trend, while CD19 +, CD4 + CD8 +, CD8 + CD45RA +, CD4 + HLA-DR +, CD8 + HLA-DR +, and CD8 + CD38 + showed downward trend. Additionally, we found certain differences between the two vaccines in neutralizing antibodies, cytokines, and lymphocyte subsets. This research is a clinical observation on the immune response after vaccination through detecting various immune indicators, which showed that the inactivated vaccines induced both humoral immunity by producing neutralizing antibodies and cellular immunity. The cellular immunity induced by these two vaccines was a Th2-biased response, and it may also lead to a mild Th1-type response.

Download Full-text

Effect of Virus Inactivating Agents on the Immunogenicity of Hantavirus Vaccines against Hemorrhagic Fever with Renal Syndrome

Biotekhnologiya ◽

10.21519/0234-2758-2020-36-2-64-73 ◽

2020 ◽

Vol 36 (2) ◽

pp. 64-73

Author(s):

S.S. Kurashova ◽

Т.К. Dzagurova ◽

M.V. Balovneva ◽

A.A. Ishmukhametov ◽

E.A. Tkachenko

Keyword(s):

Uv Radiation ◽

Russian Federation ◽

Neutralizing Antibodies ◽

Specific Activity ◽

Hemorrhagic Fever ◽

Virus Inactivation ◽

Optimal Method ◽

Inactivated Vaccines ◽

The Russian Federation ◽

And Control

Hemorrhagic fever with renal syndrome (HFRS) is an acute zoonotic disease caused by orthohantavirases Puumala, Dobrava-Belgrad (4 genotypes), Hantaan (genotype Amur) and Seoul.. In the Russian Federation, HFRS takes a leading place among all natural focal human diseases. Formalin, β-propiolactone, and ultraviolet radiation were tested to select the optimal method of virus inactivation during the development of the whole-virion vaccine against HFRS. The specific activity and the immunogenicity of the vaccine were determined, respectively, by the number of copies of viral RNA/mL and by the titer of neutralizing antibodies in the BALB/c mice blood serum in response to immunization. An analysis of the immunogenicity of vaccines inactivated with formalin, β-propiolactone or UV radiation did not reveal significant differences in the level of neutralizing antibodies they induced. At the same time, β-propiolactone has obvious technological advantages compared to formalin and UV radiation: the time of inactivation of hantavirus is reduced tenfold, neutralization of the inactivator and control of its content in the final vaccine are not required, and the amount of total protein in the vaccine decreases. hemorrhagic fever with renal syndrome, hantavirases, inactivated vaccines, neutralizing antibodies, formalin, β-propiolactone, ultraviolet

Download Full-text

Emerging Promise of Immunotherapy for Alzheimer’s Disease: A New Hope for the Development of Alzheimer’s Vaccine

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200422105156 ◽

2020 ◽

Vol 20 (13) ◽

pp. 1214-1234 ◽

Cited By ~ 4

Author(s):

Md. Tanvir Kabir ◽

Md. Sahab Uddin ◽

Bijo Mathew ◽

Pankoj Kumar Das ◽

Asma Perveen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Immune Response ◽

Neutralizing Antibodies ◽

Neurodegenerative Disorder ◽

Symptomatic Relief ◽

Aβ Oligomers ◽

Th2 Immune Response ◽

Age Related ◽

Anti Inflammatory

Background: Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the characteristics of this devastating disorder include the progressive and disabling deficits in the cognitive functions including reasoning, attention, judgment, comprehension, memory, and language. Objective: In this article, we have focused on the recent progress that has been achieved in the development of an effective AD vaccine. Summary: Currently, available treatment options of AD are limited to deliver short-term symptomatic relief only. A number of strategies targeting amyloid-beta (Aβ) have been developed in order to treat or prevent AD. In order to exert an effective immune response, an AD vaccine should contain adjuvants that can induce an effective anti-inflammatory T helper 2 (Th2) immune response. AD vaccines should also possess the immunogens which have the capacity to stimulate a protective immune response against various cytotoxic Aβ conformers. The induction of an effective vaccine’s immune response would necessitate the parallel delivery of immunogen to dendritic cells (DCs) and their priming to stimulate a Th2-polarized response. The aforesaid immune response is likely to mediate the generation of neutralizing antibodies against the neurotoxic Aβ oligomers (AβOs) and also anti-inflammatory cytokines, thus preventing the AD-related inflammation. Conclusion: Since there is an age-related decline in the immune functions, therefore vaccines are more likely to prevent AD instead of providing treatment. AD vaccines might be an effective and convenient approach to avoid the treatment-related huge expense.

Download Full-text

Assessment of Knowledge and Sources of Information on Lassa Fever Infection Among the Undergraduate Students of Ebonyi State University, Nigeria

SAGE Open ◽

10.1177/21582440211006382 ◽

2021 ◽

Vol 11 (1) ◽

pp. 215824402110063

Author(s):

MaryJoy Umoke ◽

Prince Christian Ifeanachor Umoke ◽

Chioma Adaora Nwalieji ◽

Rosemary N. Onwe ◽

Ifeanyi Emmanuel Nwafor ◽

...

Keyword(s):

Undergraduate Students ◽

Signs And Symptoms ◽

Hemorrhagic Fever ◽

Lassa Fever ◽

State University ◽

Sources Of Information ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Endemic Diseases ◽

Academic Level

Lassa fever is a zoonotic disease characterized by acute viral hemorrhagic fever, endemic in West Africa including Nigeria. The study assessed the knowledge and sources of information on Lassa fever infection among the undergraduate students of Ebonyi State University, Nigeria. This was a descriptive cross-sectional survey conducted among a sample of 389 students (18 years above). A self-administered questionnaire was used to collect data. Data were analyzed with SPSS (Version 20), and hypotheses were tested at p < .05 level of significance. Results showed that the majority of the students had good knowledge of Lassa fever description, 232 (60.75%); the signs and symptoms, 221 (57.9%); mode of transmission, 261 (68.41%); and preventive measures, 291 (76.13%). Radio, 23 (84.6%), and television, 307 (80.4%), were their major sources of information. Age ( p = .424), sex ( p = .082), and academic level ( p = .553) were not significant in the study, while faculty (social sciences; p = .000*) was strongly associated with the knowledge of Lassa fever. In conclusion, the overall knowledge of Lassa fever was good among students, though knowledge gaps were observed in the signs and symptoms. We recommend that health education on endemic diseases in the state be made a compulsory course as a general study (GST) in the university. Also, the internet, social media, and campus campaign be further used to educate and sensitize students on the effect of Lassa fever.

Download Full-text

Development of SARS-CoV-2 Specific IgG and Virus-Neutralizing Antibodies after Infection with Variants of Concern or Vaccination

Vaccines ◽

10.3390/vaccines9070700 ◽

2021 ◽

Vol 9 (7) ◽

pp. 700

Author(s):

Franziska Neumann ◽

Ruben Rose ◽

Janine Römpke ◽

Olaf Grobe ◽

Thomas Lorentz ◽

...

Keyword(s):

Immune Response ◽

Receptor Binding ◽

Neutralizing Antibodies ◽

Neutralization Test ◽

Vaccine Dose ◽

High Avidity ◽

Receptor Binding Domain ◽

Robust Immune Response ◽

Specific Igg ◽

Nucleoprotein N

The humoral immunity after SARS-CoV-2 infection or vaccination was examined. Convalescent sera after infection with variants of concern (VOCs: B.1.1.7, n = 10; B.1.351, n = 1) and sera from 100 vaccinees (Pfizer/BioNTech, BNT162b2, n = 33; Moderna, mRNA-1273, n = 11; AstraZeneca, ChAdOx1 nCoV-19/AZD1222, n = 56) were tested for the presence of immunoglobulin G (IgG) directed against the viral spike (S)-protein, its receptor-binding domain (RBD), the nucleoprotein (N) and for virus-neutralizing antibodies (VNA). For the latter, surrogate assays (sVNT) and a Vero-cell based neutralization test (cVNT) were used. Maturity of IgG was determined by measuring the avidity in an immunoblot (IB). Past VOC infection resulted in a broad reactivity of anti-S IgG (100%), anti-RBD IgG (100%), and anti-N IgG (91%), while latter were absent in 99% of vaccinees. Starting approximately two weeks after the first vaccine dose, anti-S IgG (75–100%) and particularly anti-RBD IgG (98–100%) were detectable. After the second dose, their titers increased and were higher than in the convalescents. The sVNT showed evidence of VNA in 91% of convalescents and in 80–100%/100% after first/second vaccine dose, respectively. After the second dose, an increase in VNA titer and IgGs of high avidity were demonstrated by cVNT and IB, respectively. Re-vaccination contributes to a more robust immune response.

Download Full-text

Characterization of Lassa Virus Cell Entry and Neutralization with Lassa Virus Pseudoparticles

Journal of Virology ◽

10.1128/jvi.01711-08 ◽

2009 ◽

Vol 83 (7) ◽

pp. 3228-3237 ◽

Cited By ~ 34

Author(s):

François-Loic Cosset ◽

Philippe Marianneau ◽

Geraldine Verney ◽

Fabrice Gallais ◽

Noel Tordo ◽

...

Keyword(s):

Immune Response ◽

Humoral Immune Response ◽

Neutralizing Antibodies ◽

Cell Attachment ◽

Low Ph ◽

Cell Entry ◽

Lassa Virus ◽

Ph Optimum ◽

Humoral Immune

ABSTRACT The cell entry and humoral immune response of the human pathogen Lassa virus (LV), a biosafety level 4 (BSL4) Old World arenavirus, are not well characterized. LV pseudoparticles (LVpp) are a surrogate model system that has been used to decipher factors and routes involved in LV cell entry under BSL2 conditions. Here, we describe LVpp, which are highly infectious, with titers approaching those obtained with pseudoparticles displaying G protein of vesicular stomatitis virus and their the use for the characterization of LV cell entry and neutralization. Upon cell attachment, LVpp utilize endocytic vesicles for cell entry as described for many pH-dependent viruses. However, the fusion of the LV glycoproteins is activated at unusually low pH values, with optimal fusion occurring between pH 4.5 and 3, a pH range at which fusion characteristics of viral glycoproteins have so far remained largely unexplored. Consistent with a shifted pH optimum for fusion activation, we found wild-type LV and LVpp to display a remarkable resistance to exposure to low pH. Finally, LVpp allow the fast and quantifiable detection of neutralizing antibodies in human and animal sera and will thus facilitate the study of the humoral immune response in LV infections.

Download Full-text