Immunogenic properties of the preparation containing the Chikungunya virus antigen inactivated by β-propiolactone

Introduction. Cases of Chikungunya fever have been reported in more than 100 countries in Europe, Oceania, Africa, Asia, the Caribbean, and America. The musculoskeletal disorders typical for Chikungunya fever can last from several months to a year and even lead to disability. The infection is believed to provide lifelong immunity. This factor and the lack of specific therapy make vaccination the most promising method for preventing Chikungunya fever.Materials and methods. The purified inactivated preparation with the different doses of the CHIKV antigen was injected intramuscularly to BALB/c mice twice with an interval of 14 days. Indicators of humoral and cellular immunity were assessed in dynamics in ELISA, the neutralization test and proliferation test of splenocytes. Results. The purified preparation containing the CHIKV antigen inactivated by beta-propiolactone had pronounced immunogenic properties. The most prominent immune response in ELISA and neutralization test was registered for a dose of 40 μg. Stimulation with the specific CHIKV antigen caused a pronounced proliferation of animals' splenocytes. The peak values of specific humoral and cellular immunity parameters were registered 14 days after the second injection.Discussion. The purified preparation containing the CHIKV antigen inactivated by beta-propiolactone had demonstrated the sufficient immunogenic properties. The immunizing dose of 40 μg CHIKV selected as a result of the studies caused in BALB/c mice the development of the humoral immunity characterized by the specific IgG with neutralizing activity, and the specific cell immunity characterized by the animals' splenocytes proliferation after stimulation with CHIKV antigen.Conclusion. The purified β-PL inactivated preparation of the CHIKV antigen at a dose of 40 μg to demonstrated pronounced immunogenicity in BALB/c mice after two-dose immunization. The developed preparation can be considered as promising for the prevention of Chikungunya fever using the dose and scheme tested in this study.

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Differential effects of the second SARS-CoV-2 mRNA vaccine dose on T cell immunity in naive and COVID-19 recovered individuals

10.1101/2021.03.22.436441 ◽

2021 ◽

Author(s):

Carmen Camara ◽

Daniel Lozano-Ojalvo ◽

Eduardo Lopez-Granados ◽

Estela Paz-Artal ◽

Marjorie Pion ◽

...

Keyword(s):

T Cell ◽

Severe Acute Respiratory Syndrome ◽

Cellular Immunity ◽

Rapid Development ◽

Vaccine Dose ◽

T Cell Immunity ◽

Current Standard ◽

Standard Regimen ◽

Humoral And Cellular Immunity ◽

Cell Immunity

The rapid development and deployment of mRNA-based vaccines against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to the design of accelerated vaccination schedules that have been extremely effective in naive individuals. While a two-dose immunization regimen with the BNT162b2 vaccine has been demonstrated to provide a 95% efficacy in naive individuals, the effects of the second vaccine dose in individuals who have previously recovered from natural SARS-CoV-2 infection has been questioned. Here we characterized SARS-CoV-2 spike-specific humoral and cellular immunity in naive and previously infected individuals during full BNT162b2 vaccination. Our results demonstrate that the second dose increases both the humoral and cellular immunity in naive individuals. On the contrary, the second BNT162b2 vaccine dose results in a reduction of cellular immunity in COVID-19 recovered individuals, which suggests that a second dose, according to the current standard regimen of vaccination, may be not necessary in individuals previously infected with SARS-CoV-2.

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Immunogenic profile of SARS-CoV-2 spike in individuals recovered from COVID-19

10.1101/2020.05.17.20104869 ◽

2020 ◽

Cited By ~ 1

Author(s):

Jennifer A Juno ◽

Hyon-Xhi Tan ◽

Wen Shi Lee ◽

Arnold Reynaldi ◽

Hannah G Kelly ◽

...

Keyword(s):

Vaccine Development ◽

High Plasma ◽

Relative Distribution ◽

Humoral And Cellular Immunity ◽

Follicular Helper ◽

Specific Memory ◽

Cell Immunity ◽

Global Spread ◽

A Minor ◽

Immunogenic Properties

The rapid global spread of SARS-CoV-2 and resultant mortality and social disruption have highlighted the need to better understand coronavirus immunity to expedite vaccine development efforts. Multiple candidate vaccines, designed to elicit protective neutralising antibodies targeting the viral spike glycoprotein, are rapidly advancing to clinical trial. However, the immunogenic properties of the spike protein in humans are unresolved. To address this, we undertook an in-depth characterisation of humoral and cellular immunity against SARS-CoV-2 spike in humans following mild to moderate SARS-CoV-2 infection. We find serological antibody responses against spike are routinely elicited by infection and correlate with plasma neutralising activity and capacity to block ACE2/RBD interaction. Expanded populations of spike-specific memory B cells and circulating T follicular helper cells (cTFH) were detected within convalescent donors, while responses to the receptor binding domain (RBD) constitute a minor fraction. Using regression analysis, we find high plasma neutralisation activity was associated with increased spike-specific antibody, but notably also with the relative distribution of spike-specific cTFH subsets. Thus both qualitative and quantitative features of B and T cell immunity to spike constitute informative biomarkers of the protective potential of novel SARS-CoV-2 vaccines.

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Gene-free Viral-like particles (VLPs) offer a safer alternative to inactivating or weakening viral strains for traditional vaccines. VLP-based vaccinations without adjuvants have been found to promote humoral and cellular immunity

10.31219/osf.io/9dvut ◽

2021 ◽

Author(s):

Moataz Dowaidar

Keyword(s):

Mhc Class I ◽

Cellular Immunity ◽

Metabolic Diseases ◽

Particle Surface ◽

Surface Current ◽

Specific Cell ◽

Therapeutic Vaccines ◽

Nano Structure ◽

Humoral And Cellular Immunity ◽

Recognition Motif

Nanotechnology and protein engineering helped revolutionize the invention and upgrading of immunization carriers, as well as medicine packaging and delivery systems. Viruses have been considered functioning NPs in the 21st century. This nano-structure may deliver antigens and medications to multiple locations throughout tissues and organs. Gene-free Viral-like particles (VLPs) offer a safer alternative to inactivating or weakening viral strains for traditional vaccines. This allows for the development of VLPs that can contain polyvalent antigenic structures that can also contain antigenic chemicals to target tissues. Also, they're immunogens. VLPs have also been shown to be excellent adjuvants. VLP-based vaccinations without adjuvants have been found to promote humoral and cellular immunity via the MHC class I and II route in some cases.Also used as therapeutic vaccines, presenting patients' own antigens and assisting them in the fight against chronic and metabolic diseases, as well as various types of cancers. Several vaccines created from VLP have been approved or are being tested in the clinical setting. More investigation is needed to fully assess the effectiveness, bad effects, difficulties, and benefits of VLP-based vaccinations when used for different cancers.Despite technical obstacles such as molecules appearing correctly on the particle surface, current research has provided substantial amounts of knowledge that may assist to alleviate these challenges. One option discovered in our lab is to add a sortase recognition motif (LPXTG) to the surface of distinct VLPs that may be exposed. To protect the VLP integrity, it allows proteins to be attached to the VLP surface. Use of VLP external surfaces to transport medications to a specific cell or tissue in order to treat an illness. The VLP's surface can be manipulated in order to optimize the VLP's efficacy. In order to deliver this complex to a specified target, it must be fused with molecules on the surface. Despite the fact that VLP-based vaccinations have been successful in helping to prevent disease, more work is needed to reach the optimum condition.

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Formation of humoral and cellular immunity to measles vaccine in adults

Russian Journal of Infection and Immunity ◽

10.15789/2220-7619-foh-1334 ◽

2020 ◽

Vol 10 (1) ◽

pp. 137-144

Author(s):

A. P. Toptygina ◽

Yu. Yu. Andreev ◽

M. A. Smerdova ◽

A. Yu. Zetkin ◽

T. G. Klykova

Keyword(s):

Immune Response ◽

Cellular Immunity ◽

Igg Antibodies ◽

Humoral And Cellular Immunity ◽

Measles Antibodies ◽

Iga Antibodies ◽

Measles Vaccination ◽

Specific Igg ◽

Cellular Immune ◽

Specific Igg Antibodies

Despite adherence to the policy of mass measles vaccination in the majority of countries, this infection still remains far from being fully eradicated. Measles outbreaks are reported worldwide, when the vast majority of cases are recorded in subjects of 18—35 years of age. Studies on assessing measles IgG antibody level in different regions of Russia reveal increased percentage of measles seronegative subjects among young adults. Current study was aimed at investigating formation of humoral and cellular immunity after measles vaccination in seronegative adults aged 18 to 30 years old. There were enrolled 50 measles seronegative healthy volunteers aged 18 to 30 years old. Level of anti-measles IgM and IgG antibodies was measured by ELISA (Vector-Best, Russia). Subclasses of measles specific IgG antibodies were analyzed by ELISA, by replacing IgG conjugate for IgG1, IgG2, IgG3, IgG4 conjugates, whereas measles specific IgA antibodies were estimated by ELISA with IgA conjugate (Polygnost, Russia) at a concentration of 1 μg/ml. Antibody avidity was assessed by ELISA (Euroimmun, Germany). Cell-mediated measles immunity was estimated by CD107a surface expression on CD8hi T cell subset stimulated by measles virus-derived antigens. A specific cellular response to measles antigens before vaccination was detected in 50% of examined subjects, whereas 40% samples showed no signs of cellular immune response, with 10% of remaining cases described as equivocal. It was found that 6 weeks after vaccination all vaccinated subjects developed measles specific IgG antibodies at protective level reaching 1.33 (0.85—1.82) IU/ml [Me (LQ—UQ)]. Anti-measles IgA antibodies were of 0.655 (0.423—1.208) IU/ml [Me (LQ—UQ)]. However, no measles specific IgM antibodies were detected 6 weeks after vaccination. In addition, primary type of immune response (dominant low-avidity anti-measles antibodies IgG3 subclass) to measles vaccination was observed in 24 out of 50 subjects, whereas 26 subjects developed secondary type of immune response (high-avidity anti-measles antibodies dominated by IgG1 subclass). A measles specific cellular immune response was observed in 47 of the 50 examined subjects, and in 3 volunteers it was equivocal. Further analysis revealed a cohort of subjects who were not vaccinated against measles (18 subjects), although 60% of them provided medical record on previous dual measles vaccination occurred in childhood. Another cohort consisted of subjects who had medical record of measles vaccination in childhood (32 subjects), but lost protective measles antibodies produced by plasma cells (23 subjects), and memory T cells (3 subjects), or measles antibodies and memory B cells (6 subjects) over time. Such pattern evidences that measles-specific cellular and humoral arms immune responses were developed and maintained independently of each other.

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Persistent COVID-19 Symptoms Minimally Impact the Development of SARS-CoV-2-Specific T Cell Immunity

Viruses ◽

10.3390/v13050916 ◽

2021 ◽

Vol 13 (5) ◽

pp. 916

Author(s):

Hengsheng Fang ◽

Adam D. Wegman ◽

Kianna Ripich ◽

Heather Friberg ◽

Jeffrey R. Currier ◽

...

Keyword(s):

Cellular Immunity ◽

Viral Infections ◽

T Cell Immunity ◽

N Protein ◽

Cell Immunity ◽

Public Health Challenge ◽

Human Coronaviruses ◽

Cellular Immune ◽

Persistent Viral Infections ◽

Insight Into

SARS-CoV-2 represents an unprecedented public health challenge. While the majority of SARS-CoV-2-infected individuals with mild-to-moderate COVID-19 resolve their infection with few complications, some individuals experience prolonged symptoms lasting for weeks after initial diagnosis. Persistent viral infections are commonly accompanied by immunologic dysregulation, but it is unclear if persistent COVID-19 impacts the development of virus-specific cellular immunity. To this end, we analyzed SARS-CoV-2-specific cellular immunity in convalescent COVID-19 patients who experienced eight days or fewer of COVID-19 symptoms or symptoms persisting for 18 days or more. We observed that persistent COVID-19 symptoms were not associated with the development of an overtly dysregulated cellular immune response. Furthermore, we observed that reactivity against the N protein from SARS-CoV-2 correlates with the amount of reactivity against the seasonal human coronaviruses 229E and NL63. These results provide insight into the processes that regulate the development of cellular immunity against SARS-CoV-2 and related human coronaviruses.

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Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19

Nature Communications ◽

10.1038/s41467-021-21444-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Adam K. Wheatley ◽

Jennifer A. Juno ◽

Jing J. Wang ◽

Kevin J. Selva ◽

Arnold Reynaldi ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Vaccine Development ◽

Natural Infection ◽

Population Level ◽

Cell Dynamics ◽

Follicular Helper ◽

Cell Immunity ◽

Specific Igg ◽

Over Time

AbstractThe durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with individual serum clonotypes, decay over the first 4 months post-infection. A similar decline in Spike-specific CD4+ and circulating T follicular helper frequencies occurs. By contrast, S-specific IgG+ memory B cells consistently accumulate over time, eventually comprising a substantial fraction of circulating the memory B cell pool. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent participants to 74 days, although there is probably additive protection from B cell and T cell immunity. This study indicates that SARS-CoV-2 immunity after infection might be transiently protective at a population level. Therefore, SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long-term protection.

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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.

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