Simultaneous Immunization with Multivalent Norovirus VLPs Induces Better Protective Immune Responses to Norovirus than Sequential Immunization

Human noroviruses (NoVs) are a genetically diverse, constantly evolving group of viruses. Here, we studied the effect of NoV pre-existing immunity on the success of NoV vaccinations with genetically close and distant genotypes. A sequential immunization as an alternative approach to multivalent NoV virus-like particles (VLPs) vaccine was investigated. Mice were immunized with NoV GI.3, GII.4-1999, GII.17, and GII.4 Sydney as monovalent VLPs or as a single tetravalent mixture combined with rotavirus VP6-protein. Sequentially immunized mice were primed with a trivalent vaccine candidate (GI.3 + GII.4-1999 + VP6) and boosted, first with GII.17 and then with GII.4 Sydney VLPs. NoV serum antibodies were analyzed. Similar NoV genotype-specific immune responses were induced with the monovalent and multivalent mixture immunizations, and no immunological interference was observed. Multivalent immunization with simultaneous mix was found to be superior to sequential immunization, as sequential boost induced strong blocking antibody response against the distant genotype (GII.17), but not against GII.4 Sydney, closely related to GII.4-1999, contained in the priming vaccine. Genetically close antigens may interfere with the immune response generation and thereby immune responses may be differently formed depending on the degree of NoV VLP genotype identity.

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Characterization of the Immune Response of MERS-CoV Vaccine Candidates Derived from Two Different Vectors in Mice

Viruses ◽

10.3390/v12010125 ◽

2020 ◽

Vol 12 (1) ◽

pp. 125 ◽

Cited By ~ 7

Author(s):

Entao Li ◽

Feihu Yan ◽

Pei Huang ◽

Hang Chi ◽

Shengnan Xu ◽

...

Keyword(s):

Immune Responses ◽

Antibody Response ◽

Rabies Virus ◽

Vaccine Development ◽

Vaccine Candidate ◽

Viral Vector ◽

Vaccine Vector ◽

Vaccine Candidates ◽

Cellular Immune Responses ◽

Cellular Immune

Middle East respiratory syndrome (MERS) is an acute, high-mortality-rate, severe infectious disease caused by an emerging MERS coronavirus (MERS-CoV) that causes severe respiratory diseases. The continuous spread and great pandemic potential of MERS-CoV make it necessarily important to develop effective vaccines. We previously demonstrated that the application of Gram-positive enhancer matrix (GEM) particles as a bacterial vector displaying the MERS-CoV receptor-binding domain (RBD) is a very promising MERS vaccine candidate that is capable of producing potential neutralization antibodies. We have also used the rabies virus (RV) as a viral vector to design a recombinant vaccine by expressing the MERS-CoV S1 (spike) protein on the surface of the RV. In this study, we compared the immunological efficacy of the vaccine candidates in BALB/c mice in terms of the levels of humoral and cellular immune responses. The results show that the rabies virus vector-based vaccine can induce remarkably earlier antibody response and higher levels of cellular immunity than the GEM particles vector. However, the GEM particles vector-based vaccine candidate can induce remarkably higher antibody response, even at a very low dose of 1 µg. These results indicate that vaccines constructed using different vaccine vector platforms for the same pathogen have different rates and trends in humoral and cellular immune responses in the same animal model. This discovery not only provides more alternative vaccine development platforms for MERS-CoV vaccine development, but also provides a theoretical basis for our future selection of vaccine vector platforms for other specific pathogens.

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Recombinant Mycobacterium paragordonae Expressing SARS-CoV-2 Receptor-Binding Domain as a Vaccine Candidate Against SARS-CoV-2 Infections

Frontiers in Immunology ◽

10.3389/fimmu.2021.712274 ◽

2021 ◽

Vol 12 ◽

Author(s):

Byoung-Jun Kim ◽

Hyein Jeong ◽

Hyejun Seo ◽

Mi-Hyun Lee ◽

Hyun Mu Shin ◽

...

Keyword(s):

Immune Response ◽

Single Dose ◽

Immune Responses ◽

Receptor Binding ◽

Humoral Immune Response ◽

Vaccine Candidate ◽

Binding Domain ◽

Receptor Binding Domain ◽

Live Virus ◽

Humoral Immune

At present, concerns that the recent global emergence of SARS-CoV-2 variants could compromise the current vaccines have been raised, highlighting the urgent demand for new vaccines capable of eliciting T cell-mediated immune responses, as well as B cell-mediated neutralizing antibody production. In this study, we developed a novel recombinant Mycobacterium paragordonae expressing the SARS-CoV-2 receptor-binding domain (RBD) (rMpg-RBD-7) that is capable of eliciting RBD-specific immune responses in vaccinated mice. The potential use of rMpg-RBD-7 as a vaccine for SARS-CoV-2 infections was evaluated in in vivo using mouse models of two different modules, one for single-dose vaccination and the other for two-dose vaccination. In a single-dose vaccination model, we found that rMpg-RBD-7 versus a heat-killed strain could exert an enhanced cell-mediated immune (CMI) response, as well as a humoral immune response capable of neutralizing the RBD and ACE2 interaction. In a two-dose vaccination model, rMpg-RBD-7 in a two-dose vaccination could also exert a stronger CMI and humoral immune response to neutralize SARS-CoV-2 infections in pseudoviral or live virus infection systems, compared to single dose vaccinations of rMpg-RBD or two-dose RBD protein immunization. In conclusion, our data showed that rMpg-RBD-7 can lead to an enhanced CMI response and humoral immune responses in mice vaccinated with both single- or two-dose vaccination, highlighting its feasibility as a novel vaccine candidate for SARS-CoV-2. To the best of our knowledge, this study is the first in which mycobacteria is used as a delivery system for a SARS-CoV-2 vaccine.

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Antibody response after COVID-19 mRNA vaccination in relation to age, sex, and side effects

10.1101/2021.04.19.21255714 ◽

2021 ◽

Author(s):

Paul Naaber ◽

Virge Jürjenson ◽

Ainika Adamson ◽

Epp Sepp ◽

Liina Tserel ◽

...

Keyword(s):

Immune Response ◽

Side Effects ◽

Immune Responses ◽

Antibody Response ◽

Older Individuals ◽

High Efficacy ◽

Vaccine Response ◽

Antibody Levels ◽

The Impact ◽

Older Males

AbstractBackgroundThe mRNA vaccines for SARS-CoV2 have proven highly effective and are currently used to vaccinate all age groups against COVID-19. Despite their high efficacy in clinical trials, there is limited data on the impact of age, sex, and side effects on vaccine-induced immune responses.MethodsWe here studied the development of SARS-CoV-2 Spike protein RBD domain antibodies after two doses of the Pfizer-BioNTech Comirnaty mRNA vaccine in 118 healthy volunteers and correlated their immune response with age, sex, and side effects reported after the vaccinations.FindingsOur findings show a robust immune response to the Spike protein’s RBD region after the first and the second vaccination dose. However, we also saw a decline of antibody levels at 6 weeks versus 1 week after the second dose, suggesting a waning of the immune response over time. Regardless of this, the antibody levels at 6 weeks after the second dose remained significantly higher than before the vaccination, after the first dose, or in COVID-19 convalescent individuals. We found a decreased vaccination efficacy but fewer adverse events in older individuals, and that mRNA vaccination is less efficient in older males whereas the detrimental impact of age on vaccination outcome is abolished in females at 6 weeks after the second dose.InterpretationThe Pfizer-BioNTech Comirnaty mRNA vaccine induces a strong immune response after two doses of vaccination but older individuals develop fewer side effects and decreased antibody levels at 6 weeks. The waning of anti-viral antibodies in particular in older male individuals suggests that both age and male sex act as risk factors in the immune response to the SARS-CoV-2 mRNA vaccine.FundingThe study was supported by the Centre of Excellence in Translational Genomics (EXCEGEN), and the Estonian Research Council grant PRG377 and SYNLAB Estonia.Research in contextEvidence before this studyThe first studies addressing the immune responses in older individuals after the single-dose administration of the SARS-CoV-2 mRNA vaccines have been published. We searched PubMed and medRxiv for publications on the immune response of SARS-CoV-2-mRNA vaccines, published in English, using the search terms “SARS-CoV-2”, “COVID-19”, “vaccine response”, “mRNA vaccine”, up to April 15th, 2021. To date, most mRNA vaccine response studies have not been peer-reviewed, and data on the role of age, sex and side effects on SARS-CoV-2-mRNA vaccines in real vaccination situations is limited. Some studies have found a weaker immune response in older individuals after the first dose and these have been measured at a relatively short period (within 1-2 weeks) after the first dose but little longer-term evidence exists on the postvaccination antibody persistence. Even less information is available on sex differences or correlations with mRNA vaccine side effects.Added value of this studyIn this study, we assessed the antibody response up to 6 weeks after the second dose of Pfizer-BioNTech Comirnaty mRNA vaccine in 118 individuals. Our findings show a strong initial immune response after the first dose and an even higher Spike RBD antibody levels at 1 week after the second dose, but these significantly declined at 6 weeks after the second dose. We also found a weaker immune response and faster waning of antibodies in older vaccinated individuals, which correlated with fewer side effects at the time of vaccinations. Furthermore, although overall female and male vaccinees responded similarly, we found that age-related waning of the vaccine-related antibodies was stronger amongst older males whereas in females the impact of age was lost at 6 weeks after the second dose.Implications of all the available evidenceNew mRNA vaccines are now applied worldwide as they have shown high efficacy in clinical trials. Our results show that two doses of Pfizer-BioNTech Comirnaty mRNA vaccine induce a strong antibody response to Spike RBD region but these high levels decline 1.5 months after the second dose in most of the vaccinated individuals. Nevertheless, even at 6 weeks after the second dose, they stay significantly higher than at prevaccination, after the first dose of vaccine, or in Covid-19 postinfection. These findings also implicate that fewer adverse effects may indicate lower antibody response after the vaccination and point to the need for more individualized vaccination protocols, in particular among older people.

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Immune Response of Indian Preterm Infants to Pentavalent Vaccine Varies With Component Antigens and Gestational Age

Frontiers in Immunology ◽

10.3389/fimmu.2021.592731 ◽

2021 ◽

Vol 12 ◽

Author(s):

Archana Kulkarni-Munje ◽

Nandini Malshe ◽

Sonali Palkar ◽

Aniket Amlekar ◽

Sanjay Lalwani ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Dendritic Cells ◽

Hepatitis B ◽

Immune Responses ◽

Antibody Response ◽

Preterm Infants ◽

Gestational Age ◽

Childhood Vaccination ◽

Pentavalent Vaccine

Childhood vaccination plays critical role in protecting infants from several dreaded diseases. Of the global 15 million preterm (PT) infants with compromised immune system born annually, India contributes to >3.5 million. Generation of adequate vaccine-induced immune response needs to be ensured of their protection. Immune response of Indian PT (n = 113) and full-term (FT, n = 80) infants to pentavalent vaccine administered as per the national recommendation was studied. Antibody titers against component antigens of pentavalent vaccine, immune cells profiling (T and B cells, monocytes and dendritic cells) and plasma cytokines were determined pre- and post-vaccination. Additionally, cell-mediated recall immune responses to pentavalent antigens were evaluated after short time antigenic exposure to infant PBMCs. Irrespective of gestational age (GA), all the infants developed adequate antibody response against tetanus, diphtheria, and protective but lower antibody levels for Haemophilus influenzae type-b and hepatitis B in preterm infants. Lower (~74%) protective antibody response to pertussis was independent of gestational age. PT-infants exhibited lower frequencies of CD4 T cells/dendritic cells/monocytes, increased plasma IL-10 levels and lower proliferation of central and effector memory T cells than in term-infants. Proliferative central memory response of FT-infants without anti-pertussis antibodies suggests protection from subsequent infection. Responder/non-responder PT-infants lacked immunological memory and could be infected with Bordetella. For hepatitis B, the recall response was gestational age-dependent and antibody status-independent. Humoral/cellular immune responses of PT-infants were dependent on the type of the immunogen. Preterm infants born before 32 weeks of gestation may need an extra dose of pentavalent vaccine for long lived robust immune response.

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Induction of Multifunctional Broadly Reactive T Cell Responses by a Plasmodium vivax Circumsporozoite Protein Recombinant Chimera

Infection and Immunity ◽

10.1128/iai.00480-15 ◽

2015 ◽

Vol 83 (9) ◽

pp. 3749-3761 ◽

Cited By ~ 7

Author(s):

Monica Cabrera-Mora ◽

Jairo Andres Fonseca ◽

Balwan Singh ◽

Joseli Oliveira-Ferreira ◽

Josué da Costa Lima-Junior ◽

...

Keyword(s):

Immune Response ◽

T Cell ◽

Immune Responses ◽

Plasmodium Vivax ◽

Vaccine Candidate ◽

Chimeric Protein ◽

Plasmodium Yoelii ◽

Circumsporozoite Protein ◽

Soluble Form ◽

Content Type

Plasmodium vivaxis the most widespread species ofPlasmodium, causing up to 50% of the malaria cases occurring outside sub-Saharan Africa. An effective vaccine is essential for successful control and potential eradication. A well-characterized vaccine candidate is the circumsporozoite protein (CSP). Preclinical and clinical trials have shown that both antibodies and cellular immune responses have been correlated with protection induced by immunization with CSP. On the basis of our reported approach of developing chimericPlasmodium yoeliiproteins to enhance protective efficacy, we designed PvRMC-CSP, a recombinant chimeric protein based on theP. vivaxCSP (PvCSP). In this engineered protein, regions of the PvCSP predicted to contain human T cell epitopes were genetically fused to an immunodominant B cell epitope derived from the N-terminal region I and to repeat sequences representing the two types of PvCSP repeats. The chimeric protein was expressed in soluble form with high yield. As the immune response to PvCSP has been reported to be genetically restricted in the murine model, we tested the immunogenicity of PvRMC-CSP in groups of six inbred strains of mice. PvRMC-CSP was able to induce robust antibody responses in all the mouse strains tested. Synthetic peptides representing the allelic forms of theP. vivaxCSP were also recognized to a similar extent regardless of the mouse strain. Furthermore, the immunization regimen induced high frequencies of multifunctional CD4+and CD8+PvRMC-CSP-specific T cells. The depth and breadth of the immune responses elicited suggest that immunization with PvRMC-CSP can circumvent the genetic restriction of the immune response toP. vivaxCSP. Interestingly, PvRMC-CSP was also recognized by naturally acquired antibodies from individuals living in areas where malaria is endemic. These features make PvRMC-CSP a promising vaccine candidate for further development.

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Adjuvant-dependent immune response to malarial transmission-blocking vaccine candidate antigens.

Journal of Experimental Medicine ◽

10.1084/jem.176.5.1483 ◽

1992 ◽

Vol 176 (5) ◽

pp. 1483-1487 ◽

Cited By ~ 24

Author(s):

D J Rawlings ◽

D C Kaslow

Keyword(s):

Immune Response ◽

Recombinant Protein ◽

Antibody Response ◽

Vaccine Candidate ◽

Congenic Mouse ◽

Mouse Strains ◽

Transmission Blocking ◽

Freund's Adjuvant ◽

Congenic Mouse Strains ◽

Transmission Blocking Vaccine

Immune responses in major histocompatibility complex (MHC)-disparate congenic mouse strains immunized with sexual stage malaria parasites or purified recombinant protein were adjuvant dependent. Whereas mice exhibited a limited antibody response to immunization with newly emerged Plasmodium falciparum gametes in Freund's adjuvant, all five congenic mouse strains responded to several transmission-blocking vaccine candidate antigens, when parasites were emulsified in a monophosphoryl lipid A (MPL) and trehalose dimycolate (TDM) adjuvant. The humoral response in those animals immunized with the antigen in a MPL/TDM adjuvant was helper T cell dependent, as evident by boosting of the antibody response after a second immunization. If the immunogen consisted of purified recombinant protein, then the immune response was not MHC class II limited in mice immunized with either complete Freund's adjuvant or TDM/MPL. The potential role of adjuvants in overcoming apparent immune nonresponsiveness and the implications for development of a malaria transmission-blocking vaccine are discussed.

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A Prime-Boost Strategy Using the Novel Vaccine Candidate, LemA, Protects Hamsters against Leptospirosis

Clinical and Vaccine Immunology ◽

10.1128/cvi.00034-13 ◽

2013 ◽

Vol 20 (5) ◽

pp. 747-752 ◽

Cited By ~ 25

Author(s):

Daiane D. Hartwig ◽

Karine M. Forster ◽

Thaís L. Oliveira ◽

Marta Amaral ◽

Alan J. A. McBride ◽

...

Keyword(s):

Immune Response ◽

Antibody Response ◽

Dna Vaccine ◽

Subunit Vaccine ◽

Vaccine Candidate ◽

Virulent Strain ◽

Effective Vaccine ◽

Pairwise Identity ◽

Content Type ◽

Vaccine Preparation

ABSTRACTToward developing an effective vaccine capable of conferring heterologous protection, the putative lipoprotein LemA, which presents an M3 epitope similar to that ofListeria, was evaluated as a vaccine candidate in the hamster model of leptospirosis. LemA is conserved (>70% pairwise identity) among the pathogenicLeptospiraspp., indicating its potential in stimulating a cross-protective immune response. Using different vaccination strategies, including prime-boost, DNA vaccine, and a subunit preparation, recombinant LemA conferred different levels of protection in hamsters. Significant protection against mortality was observed for the prime-boost and the DNA vaccine strategies, which showed 87.5% (P< 0.01) and 62.5% (P< 0.05) efficacy, respectively. Although the subunit vaccine preparation protected 50.0% of immunized hamsters, the level of protection was not significant. None of the hamsters in the control groups survived challenge with a virulent strain ofLeptospira interrogansserogroup Icterohaemorrhagiae. Characterization of the immune response found that the strongest antibody response was stimulated by the subunit vaccine preparation, followed by the prime-boost strategy. The DNA vaccine failed to elicit an antibody response in immunized hamsters.

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Use of Moraxella catarrhalis Lipooligosaccharide Mutants To Identify Specific Oligosaccharide Epitopes Recognized by Human Serum Antibodies

Infection and Immunity ◽

10.1128/iai.00294-09 ◽

2009 ◽

Vol 77 (10) ◽

pp. 4548-4558 ◽

Cited By ~ 12

Author(s):

Johanna M. Schwingel ◽

Katie J. Edwards ◽

Andrew D. Cox ◽

Hussein Masoud ◽

James C. Richards ◽

...

Keyword(s):

Immune Response ◽

Antibody Response ◽

Human Serum ◽

Moraxella Catarrhalis ◽

Enzyme Linked Immunosorbent Assay ◽

Human Antibody ◽

Serum Antibodies ◽

Serum Samples ◽

Carbohydrate Epitopes ◽

Tract Infections

ABSTRACT Moraxella catarrhalis is a causative agent of otitis media in children and lower respiratory tract infections in adults suffering from chronic obstructive pulmonary disease (COPD). This strict human pathogen continues to be a significant cause of disease in this broad spectrum of patients because there is no available vaccine. Although numerous putative vaccine antigens have been described, little is known about the human immune response to M. catarrhalis infection in vivo. Human serum antibodies are directed at a number of surface proteins, and lipooligosaccharides (LOS) and detoxified LOS may be an effective immunogen in mice. In this study, we used a specific LOS-based enzyme-linked immunosorbent assay (ELISA), containing the three major M. catarrhalis serotypes together with a complete series of truncated LOS mutants, to detect the development of new antibodies to specific regions of the oligosaccharide molecule. We compared serum samples from COPD patients who had recently cleared an M. catarrhalis infection to serum samples collected prior to their infection. Variability in the antibody response to LOS was observed, as some patients developed serotype-specific antibodies, others developed antibodies to the LOS of each serotype, others developed broadly cross-reactive antibodies, and some did not develop new antibodies. These newly developed human antibodies are directed at both side chains and core structures in the LOS molecule. This LOS-based ELISA can be used to dissect the human antibody response to both internal and external carbohydrate epitopes, thus providing a better understanding of the humoral immune response to M. catarrhalis LOS epitopes developed during natural infection.

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Global Stability of Delayed Viral Infection Models with Nonlinear Antibody and CTL Immune Responses and General Incidence Rate

Computational and Mathematical Methods in Medicine ◽

10.1155/2016/3903726 ◽

2016 ◽

Vol 2016 ◽

pp. 1-21 ◽

Cited By ~ 4

Author(s):

Hui Miao ◽

Zhidong Teng ◽

Zhiming Li

Keyword(s):

Immune Response ◽

Immune Responses ◽

Antibody Response ◽

Viral Infection ◽

Global Stability ◽

Incidence Rate ◽

Cytotoxic T Lymphocyte ◽

Dynamical Behavior ◽

Infection Model ◽

Ctl Immune Response

The dynamical behaviors for a five-dimensional viral infection model with three delays which describes the interactions of antibody, cytotoxic T-lymphocyte (CTL) immune responses, and nonlinear incidence rate are investigated. The threshold values for viral infection, antibody response, CTL immune response, CTL immune competition, and antibody competition, respectively, are established. Under certain assumptions, the threshold value conditions on the global stability of the infection-free, immune-free, antibody response, CTL immune response, and interior equilibria are proved by using the Lyapunov functionals method, respectively. Immune delay as a bifurcation parameter is further investigated. The numerical simulations are performed in order to illustrate the dynamical behavior of the model.

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Immune responses to inactivated and vector-based vaccines in individuals previously infected with SARS-CoV-2

10.1101/2022.01.03.22268704 ◽

2022 ◽

Author(s):

Nungruthai Suntronwong ◽

Ritthideach Yorsaeng ◽

Chompoonut Auphimai ◽

Thanunrat Thongmee ◽

Preeyaporn Vichaiwattana ◽

...

Keyword(s):

Immune Response ◽

Single Dose ◽

Immune Responses ◽

Antibody Response ◽

Specific Binding ◽

Specific Antibodies ◽

Neutralizing Activity ◽

Cell Responses ◽

Interferon Gamma Response ◽

Dose Vaccine

AbstractImmunity wanes in individuals previously infected with SARS-CoV-2, and vaccinating those individuals may help reduce reinfection. Herein, reactogenicity and immunogenicity following vaccination with inactivated (CoronaVac) and vector-based (ChAdOx1-S, AZD1222) vaccines were examined in previously infected individuals. Immune response was also compared between short and long intervals between first date of detection and vaccination. Adverse events were mild but were higher with AZD1222 than with CoronaVac. Baseline IgG-specific antibodies and neutralizing activity were significantly higher with shorter than longer intervals. With a single-dose vaccine, IgG and IgA-specific binding antibodies, neutralizing activity, and total interferon-gamma response peaked at 14 days. Immune response was significantly higher in recovered individuals than in infection-naïve individuals. Antibody response was greater with longer than shorter intervals. AZD1222 induced higher antibody and T cell responses than those of CoronaVac. Thus, to achieve immunity, individuals with prior SARS-CoV-2 exposure may require only a single dose of AZD1222 or two doses of CoronaVac to achieve the immune response. These findings supported vaccine strategies in previously infected individuals.

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