scholarly journals Intratumoral injection of the seasonal flu shot converts immunologically cold tumors to hot and serves as an immunotherapy for cancer

2019 ◽  
Vol 117 (2) ◽  
pp. 1119-1128 ◽  
Author(s):  
Jenna H. Newman ◽  
C. Brent Chesson ◽  
Nora L. Herzog ◽  
Praveen K. Bommareddy ◽  
Salvatore M. Aspromonte ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Antitumor Immunity ◽  
Infection Prevention ◽  
Seasonal Influenza ◽  
Lung Infection ◽  
Intratumoral Injection ◽  
B Cell Depletion ◽  
Regulatory B Cells ◽  
Immune Mediated ◽  
Seasonal Flu

Reprogramming the tumor microenvironment to increase immune-mediated responses is currently of intense interest. Patients with immune-infiltrated “hot” tumors demonstrate higher treatment response rates and improved survival. However, only the minority of tumors are hot, and a limited proportion of patients benefit from immunotherapies. Innovative approaches that make tumors hot can have immediate impact particularly if they repurpose drugs with additional cancer-unrelated benefits. The seasonal influenza vaccine is recommended for all persons over 6 mo without prohibitive contraindications, including most cancer patients. Here, we report that unadjuvanted seasonal influenza vaccination via intratumoral, but not intramuscular, injection converts “cold” tumors to hot, generates systemic CD8+ T cell-mediated antitumor immunity, and sensitizes resistant tumors to checkpoint blockade. Importantly, intratumoral vaccination also provides protection against subsequent active influenza virus lung infection. Surprisingly, a squalene-based adjuvanted vaccine maintains intratumoral regulatory B cells and fails to improve antitumor responses, even while protecting against active influenza virus lung infection. Adjuvant removal, B cell depletion, or IL-10 blockade recovers its antitumor effectiveness. Our findings propose that antipathogen vaccines may be utilized for both infection prevention and repurposing as a cancer immunotherapy.

scholarly journals The Usage of Influenza Vaccine to Prevent Seasonal Influenza during Pandemic COVID-19

2021 ◽  
Vol 8 (2) ◽  
pp. 93
Author(s):  
Yelvi Levani ◽  
Ayu Lidya Paramita
Keyword(s):  
Influenza Virus ◽  
Influenza Vaccine ◽  
Elderly People ◽  
Seasonal Influenza ◽  
Morbidity And Mortality ◽  
Acute Respiratory Disease ◽  
Seasonal Flu ◽  
Airborne Disease ◽  
Live Attenuated Influenza Virus ◽  
Virus Influenza

Influenza is an acute respiratory disease caused by influenza virus. Influenza can affect million people in every year and causing morbidity. Some of cases can be severe and need hospitalized, especially in elderly people. Influenza is an airborne disease and can spread rapidly. Every seasonal flu can be different because Influenza virus do mutation. Influenza vaccine can reduce morbidity and mortality. There are two types of influenza vaccine; live attenuated influenza virus (LAIV) and inactivated influenza virus (IIV). The newest type of influenza vaccine consists four types of virus (quadrivalent), therefore it gives more protection compared to the older one. Influeza vaccine is still recommended during pandemic COVID-19 because it can prevent co-infection between Influenza and COVID-19. In addition, it can reduce the morbidity and mortality during pandemic COVID-19.

scholarly journals Next generation methodology for updating HA vaccines against emerging human seasonal influenza A(H3N2) viruses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
James D. Allen ◽  
Ted M. Ross
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Next Generation ◽  
Virus Infections ◽  
Wild Type ◽  
Influenza Hemagglutinin ◽  
H3n2 Influenza

AbstractWhile vaccines remain the best tool for preventing influenza virus infections, they have demonstrated low to moderate effectiveness in recent years. Seasonal influenza vaccines typically consist of wild-type influenza A and B viruses that are limited in their ability to elicit protective immune responses against co-circulating influenza virus variant strains. Improved influenza virus vaccines need to elicit protective immune responses against multiple influenza virus drift variants within each season. Broadly reactive vaccine candidates potentially provide a solution to this problem, but their efficacy may begin to wane as influenza viruses naturally mutate through processes that mediates drift. Thus, it is necessary to develop a method that commercial vaccine manufacturers can use to update broadly reactive vaccine antigens to better protect against future and currently circulating viral variants. Building upon the COBRA technology, nine next-generation H3N2 influenza hemagglutinin (HA) vaccines were designed using a next generation algorithm and design methodology. These next-generation broadly reactive COBRA H3 HA vaccines were superior to wild-type HA vaccines at eliciting antibodies with high HAI activity against a panel of historical and co-circulating H3N2 influenza viruses isolated over the last 15 years, as well as the ability to neutralize future emerging H3N2 isolates.

scholarly journals Intratumoral injection of activated B lymphoblast in combination with PD-1 blockade induces systemic antitumor immunity with reduction of local and distal tumors

2018 ◽  
pp. e1450711 ◽  
Author(s):  
Mario M Soldevilla ◽  
Helena Villanueva ◽  
Naiara Martinez-Velez ◽  
Daniel Meraviglia-Crivelli ◽  
Marta M Alonso ◽  
...  
Keyword(s):  
Antitumor Immunity ◽  
Intratumoral Injection

scholarly journals Influenza Virus Vaccination Induces Interleukin-12/23 Receptor β1 (IL-12/23Rβ1)-Independent Production of Gamma Interferon (IFN-γ) and Humoral Immunity in Patients with Genetic Deficiencies in IL-12/23Rβ1 or IFN-γ Receptor I

2008 ◽  
Vol 15 (8) ◽  
pp. 1171-1175 ◽  
Author(s):  
Tjitske de Boer ◽  
Jaap T. van Dissel ◽  
Taco W. J. Kuijpers ◽  
Guus F. Rimmelzwaan ◽  
Frank P. Kroon ◽  
...  
Keyword(s):  
Influenza Virus ◽  
T Cell ◽  
Seasonal Influenza ◽  
Gamma Interferon ◽  
Interleukin 12 ◽  
Virus Vaccination ◽  
Cell Responses ◽  
Antibody Titers ◽  
Ifn Γ ◽  
Striking Contrast

ABSTRACT To investigate whether protective immune responses can be induced in the absence of normal interleukin-12/23/gamma interferon (IL-12/23/IFN-γ) axis signaling, we vaccinated with the seasonal influenza virus subunit vaccine two patients with complete IL-12/23 receptor β1 (IL-12/23Rβ1) deficiencies, two patients with partial IFN-γ receptor I (pIFN-γRI) deficiencies, and five healthy controls. Blood samples were analyzed before, 7 days after, and 28 days after vaccination. In most cases, antibody titers reached protective levels. Moreover, although T-cell responses in patients were lower than those observed in controls, significant influenza virus-specific T-cell proliferation, IFN-γ production, and numbers of IFN-γ-producing cells were found in all patients 7 days after the vaccination. Interestingly, influenza virus-specific IFN-γ responses were IL-12/23 independent, in striking contrast to mycobacterium-induced IFN-γ production. In conclusion, influenza virus vaccination induces IL-12/23-independent IFN-γ production by T cells and can result in sufficient humoral protection in both IL-12/23Rβ1- and pIFN-γRI-deficient individuals.

scholarly journals Broadly Reactive H2 Hemagglutinin Vaccines Elicit Cross-Reactive Antibodies in Ferrets Preimmune to Seasonal Influenza A Viruses

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Z. Beau Reneer ◽  
Amanda L. Skarlupka ◽  
Parker J. Jamieson ◽  
Ted M. Ross
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Recombinant Proteins ◽  
Human Population ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Wild Type ◽  
Influenza A Viruses ◽  
Global Pandemic

ABSTRACT Influenza vaccines have traditionally been tested in naive mice and ferrets. However, humans are first exposed to influenza viruses within the first few years of their lives. Therefore, there is a pressing need to test influenza virus vaccines in animal models that have been previously exposed to influenza viruses before being vaccinated. In this study, previously described H2 computationally optimized broadly reactive antigen (COBRA) hemagglutinin (HA) vaccines (Z1 and Z5) were tested in influenza virus “preimmune” ferret models. Ferrets were infected with historical, seasonal influenza viruses to establish preimmunity. These preimmune ferrets were then vaccinated with either COBRA H2 HA recombinant proteins or wild-type H2 HA recombinant proteins in a prime-boost regimen. A set of naive preimmune or nonpreimmune ferrets were also vaccinated to control for the effects of the multiple different preimmunities. All of the ferrets were then challenged with a swine H2N3 influenza virus. Ferrets with preexisting immune responses influenced recombinant H2 HA-elicited antibodies following vaccination, as measured by hemagglutination inhibition (HAI) and classical neutralization assays. Having both H3N2 and H1N1 immunological memory regardless of the order of exposure significantly decreased viral nasal wash titers and completely protected all ferrets from both morbidity and mortality, including the mock-vaccinated ferrets in the group. While the vast majority of the preimmune ferrets were protected from both morbidity and mortality across all of the different preimmunities, the Z1 COBRA HA-vaccinated ferrets had significantly higher antibody titers and recognized the highest number of H2 influenza viruses in a classical neutralization assay compared to the other H2 HA vaccines. IMPORTANCE H1N1 and H3N2 influenza viruses have cocirculated in the human population since 1977. Nearly every human alive today has antibodies and memory B and T cells against these two subtypes of influenza viruses. H2N2 influenza viruses caused the 1957 global pandemic and people born after 1968 have never been exposed to H2 influenza viruses. It is quite likely that a future H2 influenza virus could transmit within the human population and start a new global pandemic, since the majority of people alive today are immunologically naive to viruses of this subtype. Therefore, an effective vaccine for H2 influenza viruses should be tested in an animal model with previous exposure to influenza viruses that have circulated in humans. Ferrets were infected with historical influenza A viruses to more accurately mimic the immune responses in people who have preexisting immune responses to seasonal influenza viruses. In this study, preimmune ferrets were vaccinated with wild-type (WT) and COBRA H2 recombinant HA proteins in order to examine the effects that preexisting immunity to seasonal human influenza viruses have on the elicitation of broadly cross-reactive antibodies from heterologous vaccination.

scholarly journals Prediction, dynamics, and visualization of antigenic phenotypes of seasonal influenza viruses

2016 ◽  
Vol 113 (12) ◽  
pp. E1701-E1709 ◽  
Author(s):  
Richard A. Neher ◽  
Trevor Bedford ◽  
Rodney S. Daniels ◽  
Colin A. Russell ◽  
Boris I. Shraiman
Keyword(s):  
Influenza Virus ◽  
Seasonal Influenza ◽  
Sequence Data ◽  
Influenza Viruses ◽  
Surface Glycoprotein ◽  
Amino Acid Substitutions ◽  
Model Output ◽  
Virus Population ◽  
Web Browser ◽  
Antigenic Properties

Human seasonal influenza viruses evolve rapidly, enabling the virus population to evade immunity and reinfect previously infected individuals. Antigenic properties are largely determined by the surface glycoprotein hemagglutinin (HA), and amino acid substitutions at exposed epitope sites in HA mediate loss of recognition by antibodies. Here, we show that antigenic differences measured through serological assay data are well described by a sum of antigenic changes along the path connecting viruses in a phylogenetic tree. This mapping onto the tree allows prediction of antigenicity from HA sequence data alone. The mapping can further be used to make predictions about the makeup of the future A(H3N2) seasonal influenza virus population, and we compare predictions between models with serological and sequence data. To make timely model output readily available, we developed a web browser-based application that visualizes antigenic data on a continuously updated phylogeny.

scholarly journals The Promise of Immunotherapy in the Treatment of Hepatocellular Carcinoma

2017 ◽  
pp. 311-317 ◽  
Author(s):  
Anthony El-Khoueiry
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Therapy ◽  
Antitumor Immunity ◽  
Advanced Hepatocellular Carcinoma ◽  
Checkpoint Inhibition ◽  
Cell Infiltrate ◽  
Immune Mediated ◽  
Viral Therapy ◽  
Excellent Candidate ◽  
Tumor Environment

Advanced hepatocellular carcinoma (HCC) has presented a therapeutic challenge. Despite its heterogeneity, which is partially related to its various etiologies, it frequently arises in a background of chronic inflammation, which makes it a potentially excellent candidate for immunotherapeutic approaches. There is evidence of antitumor immunity in HCC as manifested by the cell infiltrate and its association with prognosis, the presence of tumor-associated antigens, and the reports of immune-mediated spontaneous regressions. However, both the liver itself and the tumor environment possess a diverse armamentarium of mechanisms that suppress antitumor immunity. Here, we describe the rationale for immunotherapy in HCC and discuss the emerging clinical data from various immunotherapeutic approaches including checkpoint inhibition, cell therapy, oncolytic viral therapy, and various combinatorial approaches. We also highlight the potential for various modalities to be adapted across different stages of the disease.

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