scholarly journals Boosting of SARS-CoV-2 immunity in nonhuman primates using an oral rhabdoviral vaccine

2021 ◽  
Author(s):  
Kah Whye Peng ◽  
Timothy Carey ◽  
Patrcyja Lech ◽  
Rianna Vandergaast ◽  
Miguel A Munoz-Alia ◽  
...  
Keyword(s):  
Immune Responses ◽  
Nonhuman Primates ◽  
Herd Immunity ◽  
Neutralizing Antibody ◽  
Lipid Nanoparticles ◽  
Cell Tropism ◽  
Cynomolgus Macaques ◽  
Antibody Titers ◽  
Vesicular Stomatitis ◽  
Orally Active

An orally active vaccine capable of boosting SARS-CoV-2 immune responses in previously infected or vaccinated individuals would help efforts to achieve and sustain herd immunity. Unlike mRNA-loaded lipid nanoparticles and recombinant replication-defective adenoviruses, replicating vesicular stomatitis viruses with SARS-CoV-2 spike glycoproteins (VSV-SARS2) were poorly immunogenic after intramuscular administration in clinical trials. Here, by G protein trans-complementation, we generated VSV-SARS2(+G) virions with expanded target cell tropism. Compared to parental VSV-SARS2, G-supplemented viruses were orally active in virus-naive and vaccine-primed cynomolgus macaques, powerfully boosting SARS-CoV-2 neutralizing antibody titers. Clinical testing of this oral VSV-SARS2(+G) vaccine is planned.

scholarly journals Recombinant adenovirus expressing vesicular stomatitis virus G proteins induce both humoral and cell-mediated immune responses in mice and goats

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Xiaojuan Xue ◽  
Zhaorong Yu ◽  
Hongyan Jin ◽  
Lin Liang ◽  
Jiayang Li ◽  
...  
Keyword(s):  
Immune Responses ◽  
G Proteins ◽  
Vesicular Stomatitis Virus ◽  
Neutralizing Antibodies ◽  
Recombinant Adenovirus ◽  
Neutralizing Antibody ◽  
Negative Control ◽  
Antibody Titers ◽  
Vesicular Stomatitis ◽  
Cellular Immune

Abstract Background Vesicular stomatitis (VS) is an acute, highly contagious and economically important zoonotic disease caused by the vesicular stomatitis virus (VSV). There is a need for effective and safe stable recombinant vaccine for the control of the disease. The human type 5 replication-defective adenovirus expression vector is a good way to construct recombinant vaccines. Results Three recombinant adenoviruses (rAd) were successfully constructed that expressed the VSV Indiana serotype glycoprotein (VSV-IN-G), VSV New Jersey serotype glycoprotein (VSV-NJ-G), and the G fusion protein (both serotypes of G [VSV-IN-G-NJ-G]) with potentiality to induce protective immunity. G proteins were successfully expressed with good immunogenicity. The rAds could induce the production of VSV antibodies in mice, and VSV neutralizing antibodies in goats, respectively. The neutralizing antibody titers could reach 1:32 in mice and 1:64 in goats. The rAds induced strong lymphocyte proliferation in mice and goats, which was significantly higher compared to the negative control groups. Conclusions The three rAds constructed in the study expressed VSV-G proteins and induced both humoral and cellular immune responses in mice and goats. These results lay the foundation for further studies on the use of rAds in vaccines expressing VSV-G.

scholarly journals Recombinant Adenovirus Expressing Vesicular Stomatitis Virus G Proteins Induce both Humoral and Cell-mediated Immune Responses in Mice and Goats

2021 ◽  
Author(s):  
Xiaojuan Xue ◽  
Zhaorong Yu ◽  
Hongyan Jin ◽  
Lin Liang ◽  
Jiayang Li ◽  
...  
Keyword(s):  
Immune Responses ◽  
G Proteins ◽  
Vesicular Stomatitis Virus ◽  
Neutralizing Antibodies ◽  
Recombinant Adenovirus ◽  
Neutralizing Antibody ◽  
Negative Control ◽  
Antibody Titers ◽  
Vesicular Stomatitis ◽  
Cellular Immune

Abstract Background: Vesicular stomatitis (VS) is an acute, highly contagious and economically important zoonotic disease caused by the vesicular stomatitis virus (VSV). There is a need for effective and safe stable recombinant vaccine for the control of the disease. The human type 5 replication-defective adenovirus expression vector is a good way to construct recombinant vaccines.Results: Three recombinant adenoviruses (rAd) were successfully constructed that expressed the VSV Indiana serotype glycoprotein (VSV-IN-G), VSV New Jersey serotype glycoprotein (VSV-NJ-G), and the G fusion protein (both serotypes of G [VSV-IN-G-NJ-G]) with potentiality to induce protective immunity. G proteins were successfully expressed with good immunogenicity. The rAds could induce the production of VSV antibodies in mice, and VSV neutralizing antibodies in goats, respectively. The neutralizing antibody titers could reach 1:32 in mice and 1:64 in goats. The rAds induced strong lymphocyte proliferation in mice and goats, which was significantly higher compared to the negative control groups. Conclusions: The three rAds constructed in the study expressed VSV-G proteins and induced both humoral and cellular immune responses in mice and goats. These results lay the foundation for further studies on the use of rAds in vaccines expressing VSV-G.

scholarly journals Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers

Immunity ◽  
2019 ◽  
Vol 50 (1) ◽  
pp. 241-252.e6 ◽  
Author(s):  
Matthias G. Pauthner ◽  
Joseph P. Nkolola ◽  
Colin Havenar-Daughton ◽  
Ben Murrell ◽  
Samantha M. Reiss ◽  
...  
Keyword(s):  
Nonhuman Primates ◽  
Neutralizing Antibody ◽  
Tier 2 ◽  
Antibody Titers

scholarly journals Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients

2020 ◽  
Vol 12 (564) ◽  
pp. eabd5487 ◽  
Author(s):  
Carl A. Pierce ◽  
Paula Preston-Hurlburt ◽  
Yile Dai ◽  
Clare Burn Aschner ◽  
Natalia Cheshenko ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Pediatric Patients ◽  
Neutralizing Antibody ◽  
Children And Youth ◽  
Spike Protein ◽  
Serum Concentrations ◽  
Antiviral Immune Response ◽  
Antibody Titers ◽  
Ifn Γ

Children and youth infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have milder disease than do adults, and even among those with the recently described multisystem inflammatory syndrome, mortality is rare. The reasons for the differences in clinical manifestations are unknown but suggest that age-dependent factors may modulate the antiviral immune response. We compared cytokine, humoral, and cellular immune responses in pediatric (children and youth, age <24 years) (n = 65) and adult (n = 60) patients with coronavirus disease 2019 (COVID-19) at a metropolitan hospital system in New York City. The pediatric patients had a shorter length of stay, decreased requirement for mechanical ventilation, and lower mortality compared to adults. The serum concentrations of interleukin-17A (IL-17A) and interferon-γ (IFN-γ), but not tumor necrosis factor–α (TNF-α) or IL-6, were inversely related to age. Adults mounted a more robust T cell response to the viral spike protein compared to pediatric patients as evidenced by increased expression of CD25+ on CD4+ T cells and the frequency of IFN-γ+ CD4+ T cells. Moreover, serum neutralizing antibody titers and antibody-dependent cellular phagocytosis were higher in adults compared to pediatric patients with COVID-19. The neutralizing antibody titer correlated positively with age and negatively with IL-17A and IFN-γ serum concentrations. There were no differences in anti-spike protein antibody titers to other human coronaviruses. Together, these findings demonstrate that the poor outcome in hospitalized adults with COVID-19 compared to children may not be attributable to a failure to generate adaptive immune responses.

scholarly journals Statistical Approach To Estimate Vaccinia-Specific Neutralizing Antibody Titers Using a High-Throughput Assay

2009 ◽  
Vol 16 (8) ◽  
pp. 1105-1112 ◽  
Author(s):  
Richard Kennedy ◽  
V. Shane Pankratz ◽  
Eric Swanson ◽  
David Watson ◽  
Hana Golding ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccinia Virus ◽  
High Throughput ◽  
Large Scale ◽  
Statistical Approach ◽  
Neutralizing Antibody ◽  
Neutralization Assay ◽  
Virus Neutralization Assay ◽  
Antibody Titers ◽  
High Throughput Assay

ABSTRACT Because of the bioterrorism threat posed by agents such as variola virus, considerable time, resources, and effort have been devoted to biodefense preparation. One avenue of this research has been the development of rapid, sensitive, high-throughput assays to validate immune responses to poxviruses. Here we describe the adaptation of a β-galactosidase reporter-based vaccinia virus neutralization assay to large-scale use in a study that included over 1,000 subjects. We also describe the statistical methods involved in analyzing the large quantity of data generated. The assay and its associated methods should prove useful tools in monitoring immune responses to next-generation smallpox vaccines, studying poxvirus immunity, and evaluating therapeutic agents such as vaccinia virus immune globulin.

scholarly journals IMMUNO-COV v2.0: Development and Validation of a High-Throughput Clinical Assay for Measuring SARS-CoV-2-Neutralizing Antibody Titers

mSphere ◽  
2021 ◽  
Author(s):  
Rianna Vandergaast ◽  
Timothy Carey ◽  
Samantha Reiter ◽  
Chase Lathrum ◽  
Patrycja Lech ◽  
...  
Keyword(s):  
Immune Responses ◽  
High Throughput ◽  
Causative Agent ◽  
Neutralizing Antibody ◽  
Clinical Assay ◽  
Antibody Titers ◽  
Development And Validation

Since its emergence at the end of 2019, SARS-CoV-2, the causative agent of COVID-19, has caused over 100 million infections and 2.4 million deaths worldwide. Recently, countries have begun administering approved COVID-19 vaccines, which elicit strong immune responses and prevent disease in most vaccinated individuals.

scholarly journals Recombinant protein subunit SARS-CoV-2 vaccines formulated with CoVaccine HT adjuvant induce broad, Th1 biased, humoral and cellular immune responses in mice

2021 ◽  
Author(s):  
Chih-Yun Lai ◽  
Albert To ◽  
Teri Ann S. Wong ◽  
Michael M. Lieberman ◽  
David E. Clements ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Herd Immunity ◽  
Neutralizing Antibody ◽  
Protein Subunit ◽  
Cellular Immune Responses ◽  
Oil In Water ◽  
History Of ◽  
Antibody Titers ◽  
Outbred Mice ◽  
Cellular Immune

ABSTRACTThe speed at which several COVID-19 vaccines went from conception to receiving FDA and EMA approval for emergency use is an achievement unrivaled in the history of vaccine development. Mass vaccination efforts using the highly effective vaccines are currently underway to generate sufficient herd immunity and reduce transmission of the SARS-CoV-2 virus. Despite the most advanced vaccine technology, global recipient coverage, especially in resource-poor areas remains a challenge as genetic drift in naïve population pockets threatens overall vaccine efficacy. In this study, we described the production of insect-cell expressed SARS-CoV-2 spike protein ectodomain and examined its immunogenicity in mice. We demonstrated that, when formulated with CoVaccine HT™adjuvant, an oil-in-water nanoemulsion compatible with lyophilization, our vaccine candidates elicit a broad-spectrum IgG response, high neutralizing antibody titers, and a robust, antigen-specific IFN-γ secreting response from immune splenocytes in outbred mice. Our findings lay the foundation for the development of a dry-thermostabilized vaccine that is deployable without refrigeration.

scholarly journals A Combination Adjuvant for the Induction of Potent Antiviral Immune Responses for a Recombinant SARS-CoV-2 Protein Vaccine

2021 ◽  
Vol 12 ◽  
Author(s):  
Sonia Jangra ◽  
Jeffrey J. Landers ◽  
Raveen Rathnasinghe ◽  
Jessica J. O’Konek ◽  
Katarzyna W. Janczak ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibody ◽  
Cellular Responses ◽  
Cross Protection ◽  
Protein Vaccine ◽  
Mucosal Vaccination ◽  
Adaptive Immune ◽  
Antibody Titers ◽  
High Virus

Several SARS-CoV-2 vaccines have received EUAs, but many issues remain unresolved, including duration of conferred immunity and breadth of cross-protection. Adjuvants that enhance and shape adaptive immune responses that confer broad protection against SARS-CoV-2 variants will be pivotal for long-term protection as drift variants continue to emerge. We developed an intranasal, rationally designed adjuvant integrating a nanoemulsion (NE) that activates TLRs and NLRP3 with an RNA agonist of RIG-I (IVT DI). The combination adjuvant with spike protein antigen elicited robust responses to SARS-CoV-2 in mice, with markedly enhanced TH1-biased cellular responses and high virus-neutralizing antibody titers towards both homologous SARS-CoV-2 and a variant harboring the N501Y mutation shared by B1.1.7, B.1.351 and P.1 variants. Furthermore, passive transfer of vaccination-induced antibodies protected naive mice against heterologous viral challenge. NE/IVT DI enables mucosal vaccination, and has the potential to improve the immune profile of a variety of SARS-CoV-2 vaccine candidates to provide effective cross-protection against future drift variants.

scholarly journals Immunogenicity of a Live-Attenuated Dengue Vaccine Using a Heterologous Prime-Boost Strategy in a Phase 1 Randomized Clinical Trial

2020 ◽  
Author(s):  
Leyi Lin ◽  
Michael A Koren ◽  
Kristopher M Paolino ◽  
Kenneth H Eckels ◽  
Rafael De La Barrera ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dengue Virus ◽  
Phase 1 ◽  
Vaccination Strategy ◽  
Neutralizing Antibody ◽  
Dengue Vaccine ◽  
Serious Adverse Events ◽  
Live Attenuated Vaccine ◽  
Antibody Titers ◽  
Global Health Problem

Abstract Background Dengue is a global health problem and the development of a tetravalent dengue vaccine with durable protection is a high priority. A heterologous prime-boost strategy has the advantage of eliciting immune responses through different mechanisms and therefore may be superior to homologous prime-boost strategies for generating durable tetravalent immunity. Methods In this phase 1 first-in-human heterologous prime-boost study, 80 volunteers were assigned to 4 groups and received a tetravalent dengue virus (DENV-1–4) purified inactivated vaccine (TDENV-PIV) with alum adjuvant and a tetravalent dengue virus (DENV-1–4) live attenuated vaccine (TDENV-LAV) in different orders and dosing schedules (28 or 180 days apart). Results All vaccination regimens had acceptable safety profiles and there were no vaccine-related serious adverse events. TDEN-PIV followed by TDEN-LAV induced higher neutralizing antibody titers and a higher rate of tetravalent seroconversions compared to TDEN-LAV followed by TDEN-PIV. Both TDEN-PIV followed by TDEN-LAV groups demonstrated 100% tetravalent seroconversion 28 days following the booster dose, which was maintained for most of these subjects through the day 180 measurement. Conclusions A heterologous prime-boost vaccination strategy for dengue merits additional evaluation for safety, immunogenicity, and potential for clinical benefit. Clinical Trials Registration NCT02239614.

scholarly journals Potential SARS-CoV-2 Immune Correlates of Protection in Infection and Vaccine Immunization

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 138
Author(s):  
Yongjun Sui ◽  
Yonas Bekele ◽  
Jay A. Berzofsky
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibody ◽  
Current Data ◽  
Innate Immune ◽  
Type I Interferons ◽  
Type I ◽  
Risk Of Infection ◽  
Correlates Of Protection ◽  
Immune Correlates ◽  
Antibody Titers

Both SARS-CoV-2 infections and vaccines induce robust immune responses. Current data suggested that high neutralizing antibody titers with sustained Th1 responses might correlate with protection against viral transmission and disease development and severity. In addition, genetic and innate immune factors, including higher levels of type I interferons, as well as the induction of trained immunity and local mucosal immunity also contribute to lower risk of infection and amelioration of disease severity. The identification of immune correlates of protection will facilitate the development of effective vaccines and therapeutics strategies.

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