scholarly journals A Novel Live Pichinde Virus-Based Vaccine Vector Induces Enhanced Humoral and Cellular Immunity after a Booster Dose

2015 ◽  
Vol 90 (5) ◽  
pp. 2551-2560 ◽  
Author(s):  
Rekha Dhanwani ◽  
Yanqin Zhou ◽  
Qinfeng Huang ◽  
Vikram Verma ◽  
Mythili Dileepan ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Cellular Immunity ◽  
Booster Dose ◽  
Vaccination Strategy ◽  
Vaccine Vector ◽  
Humoral And Cellular Immunity ◽  
Pichinde Virus ◽  
Boost Vaccination ◽  
Foreign Genes

ABSTRACTPichinde virus (PICV) is a bisegmented enveloped RNA virus that targets macrophages and dendritic cells (DCs) early in infection and induces strong innate and adaptive immunity in mice. We have developed a reverse genetics system to produce live recombinant PICV (strain P18) with a trisegmented RNA genome (rP18tri), which encodes all four PICV gene products and as many as two foreign genes. We have engineered the vector to express the green fluorescent protein (GFP) reporter gene (abbreviated as G in virus designations) and either the hemagglutination (HA [H]) or the nucleoprotein (NP [P]) gene of the influenza A/PR8 virus. The trisegmented viruses rP18tri-G/H and rP18tri-G/P showed slightly reduced growthin vitroand expressed HA and NP, respectively. Mice immunized with rP18tri-G/H were completely protected against lethal influenza virus challenge even 120 days after immunization. These rP18tri-based vectors could efficiently induce both neutralizing antibodies and antigen-specific T cell responses via different immunization routes. Interestingly, the immune responses were significantly increased upon a booster dose and remained at high levels even after three booster doses. In summary, we have developed a novel PICV-based live vaccine vector that can express foreign antigens to induce strong humoral and cell-mediated immunity and is ideal for a prime-and-boost vaccination strategy.IMPORTANCEWe have developed a novel Pichinde virus (PICV)-based live viral vector, rP18tri, that packages three RNA segments and encodes as many as two foreign genes. Using the influenza virus HA and NP genes as model antigens, we show that this rP18tri vector can induce strong humoral and cellular immunity via different immunization routes and can lead to protection in mice. Interestingly, a booster dose further enhances the immune responses, a feature that distinguishes this from other known live viral vectors. In summary, our study demonstrates a unique feature of this live rP18tri vector to be used as a novel vaccine platform for a prime-and-boost vaccination strategy.

Evaluation of a new viral vaccine vector in mice and rhesus macaques: J paramyxovirus (JPV)-expressing HA of influenza A virus H5N1

2021 ◽  
Author(s):  
Mathew Abraham ◽  
Ashley C. Beavis ◽  
Peng Xiao ◽  
Francois J Villinger ◽  
Zhuo Li ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Immune Responses ◽  
Respiratory Tract ◽  
Rhesus Macaques ◽  
Host Genome ◽  
Vaccine Vector ◽  
Viral Vaccine ◽  
Hpai H5n1 ◽  
Foreign Genes ◽  
H5n1 Vaccine

H5N1, an avian influenza virus, is known to circulate in many Asian countries like Bangladesh, China, Cambodia, Indonesia, and Vietnam. The current FDA-approved H5N1 vaccine has a moderate level of efficacy. A safe and effective vaccine is needed to prevent the outbreaks of highly pathogenic avian influenza (HPAI) H5N1 in humans. Non-segmented negative-sense single-stranded viruses (NNSVs) are widely used as a vector to develop vaccines for humans, animals, and poultry. NNSVs stably express foreign genes without integrating with the host genome. J Paramyxovirus (JPV) is a non-segmented negative-strand RNA virus and a member of the proposed genus Jeilongvirus in the family Paramyxoviridae . JPV-specific antibodies have been detected in rodents, bats, humans, and pigs, but the virus is not associated with disease in any species other than mice. JPV replicates in the respiratory tract of mice and efficiently expresses the virus-vectored foreign genes in tissue culture cells. In this work, we explored JPV as a vector for developing an H5N1 vaccine using intranasal delivery. We incorporated hemagglutinin (HA) of H5N1 into the JPV genome by replacing the small hydrophobic (SH) gene to generate a recombinant JPV expressing HA (rJPV-ΔSH-H5). A single intranasal administration of rJPV-ΔSH-H5 protected mice from a lethal HPAI H5N1 challenge. Intranasal vaccination of rJPV-ΔSH-H5 in rhesus macaques elicited antigen-specific humoral and cell-mediated immune responses. This work demonstrates that JPV is a promising vaccine vector. IMPORTANCE HPAI H5N1 outbreak in Southeast Asia destroyed millions of birds. Transmission of H5N1 into humans resulted in deaths in many countries. In this work, we developed a novel H5N1 vaccine candidate using JPV as a vector and demonstrated that JPV is an efficacious vaccine vector in animals. NNSVs stably express foreign genes without integrating into the host genome. JPV, an NNSV, replicates efficiently in the respiratory tract and induces robust immune responses.

Humoral and cellular immunity to hepatitis B virus-derived antigens: comparative activity of Freund complete adjuvant alum, and liposomes

1980 ◽  
Vol 30 (3) ◽  
pp. 728-733
Author(s):  
Y Sanchez ◽  
I Ionescu-Matiu ◽  
G R Dreesman ◽  
W Kramp ◽  
H R Six ◽  
...  
Keyword(s):  
Immune Response ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Immune Responses ◽  
Lipid Bilayers ◽  
Cellular Immunity ◽  
Antigen Preparation ◽  
Humoral And Cellular Immunity ◽  
B Virus ◽  
Comparative Activity

Complete Freud adjuvant, aluminum gel, and liposomes were compared for their ability to enhance the immunogenicity of an intact 22-nm HBsAg particle vaccine and an HBsAg-derived polypeptide vaccine in guinea pigs. Both humoral and cell-mediated immune responses were evaluated. The greatest immune response was obtained with complete Freund adjuvant, regardless of the antigen preparation. Aluminum gel appeared to be a better adjuvant for 22-nm HBsAg particles, but the liposomes rendered polypeptide preparations more immunogenic. The possibility that various proportions were entrapped in aqueous compartments instead of being inserted into the lipid bilayers of liposomes might account for this difference. The development of both humoral and cellular immunity was dependent upon the use of an adjuvant, because aqueous preparations had poor immunogenicity.

Host Immune Responses Against CT Antigens in Multiple Myeloma Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3492-3492 ◽  
Author(s):  
Nikoletta Lendvai ◽  
Sacha Gnjatic ◽  
Erika Ritter ◽  
Yao-Tseng Chen ◽  
Christina Coughlin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Immune Responses ◽  
Humoral Immunity ◽  
Cellular Immunity ◽  
Therapeutic Vaccine ◽  
Type I ◽  
Humoral And Cellular Immunity ◽  
Ct Antigen ◽  
Ct Antigens

Abstract The type I Melanoma Antigen GEne (MAGE) proteins belong to the Cancer-Testis (CT) family of tumor-associated antigens and are widely expressed in solid and hematologic malignancies. They are immunogenic and frequently elicit spontaneous immune responses in patients with CT antigen-expressing tumors, particularly in malignant melanoma. In melanoma patients, there is high concordance between humoral and cellular immunity. Based on these findings, CT antigens are widely investigated as potential antigenic targets for tumor-specific therapeutic vaccines. We previously showed that the type I MAGE proteins CT7 (MAGE-C1), CT10 (MAGE-C2) and MAGE-A3 were commonly detected in primary myeloma specimens, and expression of CT7 and MAGE-A3 was correlated with abnormally elevated plasma cell proliferation. These findings suggest that type I MAGE may be rational targets for vaccine therapy in multiple myeloma. Therefore, it is important to determine if type I MAGE elicit cellular or humoral immune responses in myeloma patients. To investigate this hypothesis, we assessed cellular immunity against CT7 and humoral immunity against a broad panel of CT antigens. To quantify CT7-specific cellular immunity, expanded, polyclonal pools of T cells from the bone marrow, the tumor microenvironment, were co-cultured in interferon gamma (IFNγ) ELISpot assays with autologous antigen-presenting cells (APC) transduced with in vitro transcribed mRNA coding for CT7 or control antigens. CT antigen-specific humoral immunity was examined by ELISA assay using patient serum or plasma and recombinant CT antigens. This analysis demonstrated that 2/9 patients exhibited specific T cell immunity against CT7 in their bone marrow lymphocytes as measured by IFNγ secretion. These same two patients had positive titers for other CT antigens; one for MAGE-A1 (another type I MAGE), the other for SSX-1 (a structurally distinct CT antigen). Interestingly, neither patient had positive serology for CT7. Serum from 16 other myeloma patients did not have detectible antibody titers for a broad panel of CT antigens. These results show that CT antigens are immunogenic in myeloma patients, with cellular responses against CT7 and humoral responses against MAGE-A1 and SSX-1. However, unlike other types of cancer, there appears to be discordance between humoral and cellular immunity against CT7 in multiple myeloma. This may be due in part to the significant derangements of humoral immunity in this disease. These results support further investigation of immunologic therapies targeting type I MAGE in myeloma, especially therapeutic vaccine strategies.

scholarly journals Competent immune responses to SARS-CoV-2 variants in older adults following mRNA vaccination

2021 ◽  
Author(s):  
Mladen Jergović ◽  
Jennifer L. Uhrlaub ◽  
Makiko Watanabe ◽  
Christine M. Bradshaw ◽  
Lisa M. White ◽  
...  
Keyword(s):  
Older Adults ◽  
Immune Responses ◽  
Cellular Immunity ◽  
Neutralizing Antibody ◽  
Humoral And Cellular Immunity ◽  
Age Cohorts ◽  
Receptor Repertoire ◽  
Depth Analysis ◽  
Repertoire Diversity ◽  
Antibody Titers

Aging is associated with a reduced magnitude of primary immune responses to vaccination and constriction of immune receptor repertoire diversity. Clinical trials demonstrate high efficacy of mRNA based SARS-CoV-2 vaccines in older adults but concerns about virus variant escape have not been well addressed. We have conducted an in-depth analysis of humoral and cellular immunity against an early-pandemic viral isolate and compared that to the P.1. (Gamma) and B.1.617.2 (Delta) variants, as well to a B.1.595 SARS-CoV-2 isolate bearing Spike mutation E484Q, in <55 and >65 age cohorts of mRNA vaccine recipients. As reported, robust immunity required the second dose of vaccine. Older vaccine recipients exhibited an expected 3-5x reduction (but not a complete loss) in neutralizing antibody titers against both P.1. (Gamma) and the B.1.595 virus at the peak of the boosted response. However, older vaccinees manifest robust cellular immunity against early-pandemic SARS-CoV-2 and more recent variants, which remained statistically comparable to the adult group. While the duration of these immune responses remains to be determined over longer periods of time, these results provide reasons for optimism regarding vaccine protection of older adults against SARS-CoV-2 variants and inform thinking about boost vaccination with variant vaccines.

scholarly journals High Prevalence of Humoral and Cellular Immunity to Influenza Viruses in Preschool Children Living in Addis Ababa, Ethiopia

2017 ◽  
Vol 4 (1) ◽  
Author(s):  
Jennifer L. Dembinski ◽  
Adane Mihret ◽  
Solomon A. Yimer ◽  
Bamlak Tessema ◽  
Mai-Chi Trieu ◽  
...  
Keyword(s):  
Preschool Children ◽  
Immune Responses ◽  
Cellular Immunity ◽  
Influenza A ◽  
Addis Ababa ◽  
Interferon Γ ◽  
Influenza Viruses ◽  
Influenza B ◽  
Humoral And Cellular Immunity ◽  
Cellular Immune

Abstract Background Influenza in children who reside in tropical and subtropical regions has until recently been regarded as insignificant. However, new evidence suggests that it significantly impacts hospitalization and promotes secondary bacterial coinfections. Ethiopia is situated in a subtropical area where influenza viruses are likely to circulate year round. Methods Clinical data were recorded in a cohort of 103 healthy preschool children recruited in Addis Ababa, Ethiopia. Humoral and cellular immune responses to influenza virus were determined by hemagglutination inhibition (HI) and interferon-γ enzyme-linked immunospot assays. Results Ninety-six percent of the children (2–5 years old) had pre-existing HI antibody responses to 1 or more of the circulating influenza A subtypes, H1N1 (51%), H3N2 (86%), or influenza B (51%) strains. At the age of 4, all children had been infected with at least 1 strain, and 75% had been infected with 2–4 different viral strains. CD4+ and CD8+ T-cell responses against conserved viral antigens increased with repeated exposures, indicating boosting of cross-reactive cellular immunity. Malnutrition did not seem to affect these immune responses to influenza. Conclusions Influenza is highly prevalent among children in this area of Ethiopia. Due to the risk of secondary bacterial pneumonia, increased influenza awareness might benefit child health.

scholarly journals Protective Cellular Immunity Against Influenza Virus Induced by Plasmid Inoculation of Newborn Mice

1998 ◽  
Vol 5 (3) ◽  
pp. 197-210 ◽  
Author(s):  
Adrian Bot ◽  
Simona Bot ◽  
Adolfo García-Sastre ◽  
Constantin Bona
Keyword(s):  
Influenza Virus ◽  
Cellular Immunity ◽  
Early Period ◽  
Tolerance Induction ◽  
Vaccination Strategy ◽  
Influenza Viruses ◽  
Lethal Challenge ◽  
Newborn Mice ◽  
Adult Mice ◽  
Multiple Strains

Neonate organisms display an intrinsic disability to mount effective immune responses to infectious agents or conventional vaccines. Whereas low. doses of antigens trigger a suboptimal response, higher doses are frequently associated with tolerance induction. We investigated the ability of a plasmid-expressing nucleoprotein of influenza virus to prime a specific cellular immune response when administered to newborn mice. We found that persistent exposure to antigen following plasmid inoculation of neonates leads to a vigorous priming of specific CTLs rather than tolerance induction. The CTLs were cross-reactive against multiple strains of type A influenza viruses and produced IFNγbut no IL-4. The immunity triggered by plasmid inoculation of neonates was protective in terms of pulmonary virus clearance as well as survival rate following lethal challenge with influenza virus. Whereas the persistence of the plasmid at the site of injection was readily demonstrable in adult mice at 3 months after inoculation, mice immunized as newborns displayed no plasmid at 3 months and very little at 1 month after injection. Thus, DNA-based immunization of neonates may prove an effective and safe vaccination strategy for induction of cellular immunity against microbes that cause serious infectious diseases in the early period of life.

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