AddaVax Formulated with PolyI:C as a Potential Adjuvant of MDCK-based Influenza Vaccine Enhances Local, Cellular, and Antibody Protective Immune Response in Mice

AbstractPoor immune responses to inactivated influenza vaccine can be improved by effective and safe adjuvants to increase antibody titers and cellular protective response. In our study, AddaVax and PolyI:C combined adjuvant (AP adjuvant) were used for influenza vaccine development. After immunizing BALB/c mice and Wistar rats intramuscularly, Split inactivated H3N2 vaccine adjuvanted with AP elicited higher serum hemagglutination-inhibition antibodies and IgG titers. We demonstrated that AP induced a transient innate immune cytokines production at the injection site, induced H3N2 uptake by DCs, increased recruitment of monocytes and DCs in LNs, and promoted H3N2 vaccine migration; AP facilitated vaccines to induce a vigorous adaptive immune response. Besides, AP showed good safety as shown by lymph nodes (LNs) size, spleens index of BALB/c mice, and weight changes and C-reaction protein level of BALB/c mice and Wistar rats after repeated administration of high-dose vaccine with or without adjuvant. These findings indicate that AP is a potential novel adjuvant and can be used as a safe and effective adjuvant for MDCK-based influenza inactivated vaccine to induce cellular and antibody protective response.

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LB14. Safety and Immunogenicity of High-Dose Quadrivalent Influenza Vaccine Administered by Intramuscular Route in Subjects Aged 65 Years and Older

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy229.2188 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S764-S764 ◽

Cited By ~ 1

Author(s):

Lee-Jah Chang ◽

Ya Meng ◽

Helene Janosczyk ◽

Victoria Landolfi ◽

H Keipp Talbot ◽

...

Keyword(s):

United States ◽

Immune Response ◽

Influenza Vaccine ◽

Standard Dose ◽

The United States ◽

Influenza Vaccines ◽

High Dose ◽

Post Vaccination ◽

B Lineage ◽

Research Grant

Abstract Background Older adults (≥65 years of age) remain at increased risk of influenza because they do not respond to standard dose influenza vaccines as well as younger adults. A high dose, inactivated trivalent influenza vaccine, IIV3-HD, containing four times the antigen content (60 µg hemagglutinin per influenza strain) of standard-dose influenza vaccines has been available in the United States since 2010. Two distinct B influenza lineages (Victoria and Yamagata) have co-circulated for over a decade, making it difficult to predict which will predominate the next season. IIV4-HD has been developed to address the frequent influenza B strain mismatches by incorporating a strain from each B lineage. This pivotal Phase III study evaluated the safety and immunogenicity of IIV4-HD as compared with two IIV3-HD vaccines. Method A randomized, modified double-blind, multicenter study (NCT03282240) was conducted in 2670 healthy subjects in the United States, who were randomly assigned to receive IIV4-HD, a licensed IIV3-HD, or an IIV3-HD with the alternate B influenza strain. Using the hemagglutinin inhibition (HAI) assay at baseline and 28 days after vaccination, post-vaccination geometric mean titers and seroconversion rates were measured. Safety data were collected through 6 months post-vaccination. Result IIV4-HD was noninferior to the licensed IIV3-HD and the investigational IIV3-HD (containing the alternate B strain) for all four influenza strains as assessed by HAI GMTs and seroconversion rates. Moreover, IIV4-HD induced a superior immune response (HAI GMTs and seroconversion rates) compared with the immune response induced by the IIV3-HD that does not contain the corresponding B strain. Reactogenicity profiles were comparable across all study groups. Most unsolicited adverse events were of Grade 1 or Grade 2 intensity. One serious adverse event considered related by the Investigator was reported in the IIV4-HD group. Conclusion Vaccination of adults 65 years of age and older with IIV4-HD was found to be noninferior to two IIV3-HD vaccines with a similar safety profile. The addition of a second B lineage strain does not adversely affect the safety or immunogenicity profile of IIV4-HD compared with IIV3-HD. Disclosures L. J. Chang, Sanofi Pasteur: Employee, Salary. Y. Meng, Sanofi Pasteur: Employee, Salary. H. Janosczyk, Sanofi Pasteur: Employee, Salary. V. Landolfi, Sanofi Pasteur: Employee, Salary. H. K. Talbot, Sanofi Pasteur: Investigator, Research grant. Gilead: Investigator, Research grant. MedImmune: Investigator, Research grant. Vaxinnate: Safety Board, none. Seqirus: Safety Board, none.

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Shigellosis: Innate Mechanisms of Inflammatory Destruction of the Intestinal Epithelium, Adaptive Immune Response, and Vaccine Development

Critical Reviews in Immunology ◽

10.1615/critrevimmunol.v23.i56.20 ◽

2003 ◽

Vol 23 (5-6) ◽

pp. 371-401 ◽

Cited By ~ 47

Author(s):

Armelle Phalipon ◽

P. J. Sansonetti

Keyword(s):

Immune Response ◽

Intestinal Epithelium ◽

Vaccine Development ◽

Adaptive Immune Response ◽

Adaptive Immune

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Immunogenicity Measures of Influenza Vaccines: A Study of 1164 Registered Clinical Trials

Vaccines ◽

10.3390/vaccines8020325 ◽

2020 ◽

Vol 8 (2) ◽

pp. 325 ◽

Cited By ~ 1

Author(s):

Alexander Domnich ◽

Ilaria Manini ◽

Donatella Panatto ◽

Giovanna Elisa Calabrò ◽

Emanuele Montomoli

Keyword(s):

Immune Response ◽

Influenza Vaccine ◽

Humoral Immune Response ◽

Adaptive Immune Response ◽

Point Of View ◽

Influenza Vaccines ◽

Study Phase ◽

Cell Mediated Immunity ◽

Humoral Immune ◽

Immunological Assays

Influenza carries an enormous burden each year. Annual influenza vaccination is the best means of reducing this burden. To be clinically effective, influenza vaccines must be immunogenic, and several immunological assays to test their immunogenicity have been developed. This study aimed to describe the patterns of use of the various immunological assays available to measure the influenza vaccine-induced adaptive immune response and to determine its correlates of protection. A total of 76.5% of the studies included in our analysis measured only the humoral immune response. Among these, the hemagglutination-inhibition assay was by far the most widely used. Other, less common, humoral immune response assays were: virus neutralization (21.7%), enzyme-linked immunosorbent (10.1%), single radial hemolysis (4.6%), and assays able to quantify anti-neuraminidase antibodies (1.7%). By contrast, cell-mediated immunity was quantified in only 23.5% of studies. Several variables were significantly associated with the use of single assays. Specifically, some influenza vaccine types (e.g., adjuvanted, live attenuated and cell culture-derived or recombinant), study phase and study sponsorship pattern were usually found to be statistically significant predictors. We discuss the principal findings and make some suggestions from the point of view of the various stakeholders.

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Will SARS-CoV-2 Infection Elicit Long-Lasting Protective or Sterilising Immunity? Implications for Vaccine Strategies (2020)

Frontiers in Immunology ◽

10.3389/fimmu.2020.571481 ◽

2020 ◽

Vol 11 ◽

Author(s):

David S. Kim ◽

Sarah Rowland-Jones ◽

Ester Gea-Mallorquí

Keyword(s):

Immune Response ◽

Protective Immunity ◽

Vaccine Development ◽

Adaptive Immune Response ◽

Human Immune System ◽

Adaptive Immune ◽

Global Pandemic ◽

Human Immune ◽

Novel Coronavirus

In December 2019, an outbreak of a novel coronavirus (SARS-CoV-2) in Wuhan, China resulted in the current COVID-19 global pandemic. The human immune system has not previously encountered this virus, raising the important question as to whether or not protective immunity is generated by infection. Growing evidence suggests that protective immunity can indeed be acquired post-infection—although a handful of reinfection cases have been reported. However, it is still unknown whether the immune response to SARS-CoV-2 leads to some degree of long-lasting protection against the disease or the infection. This review draws insights from previous knowledge regarding the nature and longevity of immunity to the related virus, SARS-CoV, to fill the gaps in our understanding of the immune response to SARS-CoV-2. Deciphering the immunological characteristics that give rise to protective immunity against SARS-CoV-2 is critical to guiding vaccine development and also predicting the course of the pandemic. Here we discuss the recent evidence that characterises the adaptive immune response against SARS-CoV-2 and its potential implications for the generation of memory responses and long-term protection.

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2737. Comparison of Antibody Responses to Vaccination with a Pure Hemagglutinin Influenza Vaccine (rHA) and Licensed Subvirion Influenza Vaccine Made in Eggs or Cell Culture in Adults 60 Years and Older

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2415 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S963-S963

Author(s):

Moumita Sarker ◽

Angela Branche ◽

Michael Peasley ◽

David Topham

Keyword(s):

Older Adults ◽

Influenza Vaccine ◽

Vaccine Development ◽

Standard Dose ◽

Geometric Mean ◽

The United States ◽

Antibody Responses ◽

Influenza B Virus ◽

Influenza B ◽

High Dose

Abstract Background Influenza is associated with increased mortality and morbidity for older adults. High-dose egg grown trivalent inactivated influenza vaccine (Fluzone HD) is safe and provides superior immune responses in older adults compared with standard dose (SD). Recently, two new vaccines have been licensed in the United States: cell cultured inactivated vaccine FluCelVax and baculovirus-expressed pure hemagglutinin (HA) vaccine FluBlok. Data from one study demonstrated higher efficacy with FluBlok than SD Fluzone in older adults. There is no data however comparing HD Fluzone to FluBlok and FluCelVax has not been studied at all. The purpose of this study was to assess hemagglutinin inhibition (HAI) antibody responses to vaccination with three vaccines in adults ≥ 60 years. Methods Adults ≥ 60 years were randomly assigned to receive one of the three vaccines: Fluzone HD, FluBlok and FluCelVax (Figure 1). Active influenza-like illness (ILI) surveillance was conducted with bi-weekly telephone calls. Serum samples were collected prior to vaccination and at day 7, 14, 28 and 180 and antibody responses assessed by HAI titer to A/Singapore/INFIMH-16–0019(H3N2), A/Michigan/45/2015(H1N1) and B/Colorado/6/2017 (Victoria) viruses as well as a circulating H3N2 strain. The primary endpoint was a 4-fold rise in antibody titer at day 28. Results 48 subjects were vaccinated in October 2018. Mean age was 69 and 65% were female. Two subjects reported ILI symptoms and one was positive for infection (H1N1). A majority of subjects demonstrated pre-existing antibody to all three viruses (Figure 2, Blue). Geometric mean titers (GMT) for antibody responses to the influenza A viruses were similar for FluBlok (FB) and HD Fluzone (FZ) but lower for FluCelVax(FCB) subjects (Figure 2, Orange). A higher percent of FlubBlok subjects demonstrated 4-fold rise in antibody responses to the Victoria influenza B virus (FB GMT 140 vs. FZ GMT 116, P = 0.26). Conclusion In this small study, antibody responses were similar or higher in older adults after vaccination with FluBlok compared with Fluzone HD with lower responses demonstrated with FluCelvax. Emerging concerns about HA egg adaptation during vaccine development compels further study to determine the appropriate vaccination strategy for this vulnerable population. Disclosures All authors: No reported disclosures.

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Role for Gr-1+Cells in the Control of High-Dose Mycobacterium bovis Recombinant BCG

Clinical and Vaccine Immunology ◽

10.1128/cvi.00363-14 ◽

2014 ◽

Vol 21 (8) ◽

pp. 1120-1127 ◽

Cited By ~ 1

Author(s):

Michael W. Panas ◽

Norman L. Letvin

Keyword(s):

Immune Response ◽

Mycobacterium Bovis ◽

Bioluminescence Imaging ◽

Adaptive Immune Response ◽

Vaccine Vector ◽

High Dose ◽

Mycobacterial Antigen ◽

Content Type ◽

Inflammatory Monocytes ◽

Recombinant Bcg

ABSTRACTMycobacterium bovisbacillus Calmette-Guérin (BCG) is an attractive target for development as a live vaccine vector delivering transgenic antigens from HIV and other pathogens. Most studies aimed at defining the clearance of BCG have been performed at doses between 102and 104CFU. Interestingly, however, recombinant BCG (rBCG) administered at doses of >106CFU effectively generates antigen-specific T-cell responses and primes for heterologous boost responses. Thus, defining clearance at high doses might aid in the optimization of rBCG as a vector. In this study, we used bioluminescence imaging to examine the kinetics of rBCG transgene expression and clearance in mice immunized with 5 × 107CFU rBCG expressing luciferase. Similar to studies using low-dose rBCG, our results demonstrate that the adaptive immune response is necessary for long-term control of rBCG beginning 9 days after immunizing mice. However, in contrast to these reports, we observed that the majority of mycobacterial antigen was eliminated prior to day 9. By examining knockout and antibody-mediated depletion mouse models, we demonstrate that the rapid clearance of rBCG occurs in the first 24 h and is mediated by Gr-1+cells. As Gr-1+granulocytes have been described as having no impact on BCG clearance at low doses, our results reveal an unappreciated role for Gr-1+neutrophils and inflammatory monocytes in the clearance of high-dose rBCG. This work demonstrates the potential of applying bioluminescence imaging to rBCG in order to gain an understanding of the immune response and increase the efficacy of rBCG as a vaccine vector.

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The humoral immune response to high-dose influenza vaccine in persons with monoclonal B-cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL)

Vaccine ◽

10.1016/j.vaccine.2021.01.001 ◽

2021 ◽

Vol 39 (7) ◽

pp. 1122-1130

Author(s):

Jennifer A. Whitaker ◽

Sameer A. Parikh ◽

Tait D. Shanafelt ◽

Neil E. Kay ◽

Richard B. Kennedy ◽

...

Keyword(s):

Immune Response ◽

Chronic Lymphocytic Leukemia ◽

Influenza Vaccine ◽

B Cell ◽

Humoral Immune Response ◽

Lymphocytic Leukemia ◽

High Dose ◽

Humoral Immune

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The Sex Differences of Morphology and Immunology of SIRS of Newborn Wistar Rats

International Scholarly Research Notices ◽

10.1155/2014/190749 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

A. M. Kosyreva

Keyword(s):

Immune Response ◽

Sex Differences ◽

Wistar Rats ◽

Inflammatory Diseases ◽

Reproductive Age ◽

Control Group ◽

High Dose ◽

Spleen Cells ◽

Male And Female ◽

Males And Females

The sex differences of infection and inflammatory diseases particularly appear at reproductive age and depend on the sex hormone level, varied between male and female. There are a few sets of data about the sex differences of infection and inflammatory diseases course, including systemic inflammatory response syndrome (SIRS) and sepsis, of newborns. The aim of our research was the estimation of morphological and immunological manifestation of SIRS of the newborn Wistar rats. Investigations were carried out on male and female two-day-old Wistar rats (10–12 g). SIRS was modeled by intraperitoneal injection of LPS (E. coli, O26: B6 strain, Sigma) in high dose—15 mg/kg. We did not find out any sex differences of the liver lesions severity between newborn males and females after LPS injection. The levels of endotoxin and estradiol in the serum, as the number of neutrophils in the intra-alveolar septa of the lungs, were higher in males than females with SIRS. Production of IL-2 and TNF-α by the spleen cells of males was higher than that in control group that reflects polarization predominantly on the Th1-type immune response. The secretion of IL-2, TNF-α, and IFN-γ by ConA activated spleen cells of females decreased that reflects the suppression of Th1-type immune response. We suppose that the LPS administration in the high dose causes the multidirectional reaction of the immune system of neonatal males and females Wistar rats.

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Hide and Seek: The Interplay Between Zika Virus and the Host Immune Response

Frontiers in Immunology ◽

10.3389/fimmu.2021.750365 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lim Jack Lee ◽

Thamil Vaani Komarasamy ◽

Nur Amelia Azreen Adnan ◽

William James ◽

Vinod RMT Balasubramaniam

Keyword(s):

Immune Response ◽

Zika Virus ◽

Large Scale ◽

Vaccine Development ◽

Sexual Transmission ◽

Adaptive Immune Response ◽

Host Immune Response ◽

Interferon Response ◽

Current Status ◽

Successful Infection

Zika virus (ZIKV) received worldwide attention over the past decade when outbreaks of the disease were found to be associated with severe neurological syndromes and congenital abnormalities. Unlike most other flaviviruses, ZIKV can spread through sexual and transplacental transmission, adding to the complexity of Zika pathogenesis and clinical outcomes. In addition, the spread of ZIKV in flavivirus-endemic regions, and the high degree of structural and sequence homology between Zika and its close cousin Dengue have raised questions on the interplay between ZIKV and the pre-existing immunity to other flaviviruses and the potential immunopathogenesis. The Zika epidemic peaked in 2016 and has affected over 80 countries worldwide. The re-emergence of large-scale outbreaks in the future is certainly a possibility. To date, there has been no approved antiviral or vaccine against the ZIKV. Therefore, continuing Zika research and developing an effective antiviral and vaccine is essential to prepare the world for a future Zika epidemic. For this purpose, an in-depth understanding of ZIKV interaction with many different pathways in the human host and how it exploits the host immune response is required. For successful infection, the virus has developed elaborate mechanisms to escape the host response, including blocking host interferon response and shutdown of certain host cell translation. This review provides a summary on the key host factors that facilitate ZIKV entry and replication and the mechanisms by which ZIKV antagonizes antiviral innate immune response and involvement of adaptive immune response leading to immunopathology. We also discuss how ZIKV modulates the host immune response during sexual transmission and pregnancy to induce infection, how the cross-reactive immunity from other flaviviruses impacts ZIKV infection, and provide an update on the current status of ZIKV vaccine development.

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