Vaccines

Research

14 pages, 2647 KiB

Open AccessArticle

Stimulation of Potent Humoral and Cellular Immunity via Synthetic Dual-Antigen MVA-Based COVID-19 Vaccine COH04S1 in Cancer Patients Post Hematopoietic Cell Transplantation and Cellular Therapy

by Flavia Chiuppesi, Sandra Ortega-Francisco, Miguel-Angel Gutierrez, Jing Li, Minh Ly, Katelyn Faircloth, Jada Mack-Onyeike, Corinna La Rosa, Sandra Thomas, Qiao Zhou, Jennifer Drake, Cynthia Slape, Paolo Fernando, Wasima Rida, Teodora Kaltcheva, Alba Grifoni, Alessandro Sette, Angela Patterson, Shannon Dempsey, Brian Ball, Haris Ali, Amandeep Salhotra, Anthony Stein, Nitya Nathwani, Michael Rosenzweig, Liana Nikolaenko, Monzr M. Al Malki, Jana Dickter, Deepa D. Nanayakkara, Alfredo Puing, Stephen J. Forman, Randy A. Taplitz, John A. Zaia, Ryotaro Nakamura, Felix Wussow, Don J. Diamond and Sanjeet S. Dadwal Show full author list Hide full author list

Vaccines 2023, 11(9), 1492; https://doi.org/10.3390/vaccines11091492 - 15 Sep 2023

Viewed by 3653

Abstract

Hematopoietic cell transplantation (HCT) and chimeric antigen receptor (CAR)-T cell patients are immunocompromised, remain at high risk following SARS-CoV-2 infection, and are less likely than immunocompetent individuals to respond to vaccination. As part of the safety lead-in portion of a phase 2 clinical [...] Read more.

Hematopoietic cell transplantation (HCT) and chimeric antigen receptor (CAR)-T cell patients are immunocompromised, remain at high risk following SARS-CoV-2 infection, and are less likely than immunocompetent individuals to respond to vaccination. As part of the safety lead-in portion of a phase 2 clinical trial in patients post HCT/CAR-T for hematological malignancies (HM), we tested the immunogenicity of the synthetic modified vaccinia Ankara-based COVID-19 vaccine COH04S1 co-expressing spike (S) and nucleocapsid (N) antigens. Thirteen patients were vaccinated 3–12 months post HCT/CAR-T with two to four doses of COH04S1. SARS-CoV-2 antigen-specific humoral and cellular immune responses, including neutralizing antibodies to ancestral virus and variants of concern (VOC), were measured up to six months post vaccination and compared to immune responses in historical cohorts of naïve healthy volunteers (HV) vaccinated with COH04S1 and naïve healthcare workers (HCW) vaccinated with the FDA-approved mRNA vaccine Comirnaty^® (Pfizer, New York, NY, USA). After one or two COH04S1 vaccine doses, HCT/CAR-T recipients showed a significant increase in S- and N-specific binding antibody titers and neutralizing antibodies with potent activity against SARS-CoV-2 ancestral virus and VOC, including the highly immune evasive Omicron XBB.1.5 variant. Furthermore, vaccination with COH04S1 resulted in a significant increase in S- and N-specific T cells, predominantly CD4⁺ T lymphocytes. Elevated S- and N-specific immune responses continued to persist at six months post vaccination. Furthermore, both humoral and cellular immune responses in COH04S1-vaccinated HCT/CAR-T patients were superior or comparable to those measured in COH04S1-vaccinated HV or Comirnaty^®-vaccinated HCW. These results demonstrate robust stimulation of SARS-CoV-2 S- and N-specific immune responses including cross-reactive neutralizing antibodies by COH04S1 in HM patients post HCT/CAR-T, supporting further testing of COH04S1 in immunocompromised populations. Full article

(This article belongs to the Special Issue New Trends in SARS-CoV-2 Variants and Vaccines)

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15 pages, 3326 KiB

Open AccessArticle

Heterologous COVID-19 Vaccination and Booster with mRNA Vaccine Provide Enhanced Immune Response in Patients with Cirrhosis: A Prospective Observational Study

by Pimsiri Sripongpun, Nawamin Pinpathomrat, Ratchanon Sophonmanee, Jomkwan Ongarj, Purilap Seepathomnarong, Bunya Seeyankem, Naichaya Chamroonkul, Teerha Piratvisuth and Apichat Kaewdech

Vaccines 2023, 11(9), 1455; https://doi.org/10.3390/vaccines11091455 - 4 Sep 2023

Cited by 1 | Viewed by 1127

Abstract

This study aimed to evaluate the antibody and cellular responses to different coronavirus 2019 (COVID-19) vaccination regimens in patients with cirrhosis and to assess the antibody response after a vaccine booster. We conducted a prospective observational study of 89 patients with cirrhosis and [...] Read more.

This study aimed to evaluate the antibody and cellular responses to different coronavirus 2019 (COVID-19) vaccination regimens in patients with cirrhosis and to assess the antibody response after a vaccine booster. We conducted a prospective observational study of 89 patients with cirrhosis and 41 healthy volunteers who received two COVID-19 vaccine doses. Next, we prospectively evaluated 24 patients with cirrhosis who received a booster COVID-19 vaccine dose. In both studies, blood samples were collected before and 4 weeks after vaccination, and anti-spike receptor-binding domain protein IgG levels, T-cell phenotypes, and effector functions were assessed. The heterologous vaccine regimen (CoronaVac [SV]/AstraZeneca [AZ]) produced a better antibody response and CD4+IFNg+ T cell response compared to homogeneous vaccine regimens. The antibody response after the second dose of the vaccine was similar in patients with cirrhosis and healthy volunteers. Patients who received a booster dose of the mRNA vaccine had significantly increased antibody titers compared to those who received the AZ vaccine. In patients with cirrhosis, heterologous vaccination with SV/AZ resulted in a better immune response than the AZ/AZ and SV/SV regimens. Moreover, a booster dose of the mRNA vaccine led to a greater increase in antibody titers compared to the AZ vaccine. Full article

(This article belongs to the Special Issue New Trends in SARS-CoV-2 Variants and Vaccines)

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17 pages, 2673 KiB

Open AccessArticle

Oral Immunization with rVSV Bivalent Vaccine Elicits Protective Immune Responses, Including ADCC, against Both SARS-CoV-2 and Influenza A Viruses

by Maggie Jing Ouyang, Zhujun Ao, Titus A. Olukitibi, Peter Lawrynuik, Christopher Shieh, Sam K. P. Kung, Keith R. Fowke, Darwyn Kobasa and Xiaojian Yao

Vaccines 2023, 11(9), 1404; https://doi.org/10.3390/vaccines11091404 - 23 Aug 2023

Cited by 1 | Viewed by 1905

Abstract

COVID-19 and influenza both cause enormous disease burdens, and vaccines are the primary measures for their control. Since these viral diseases are transmitted through the mucosal surface of the respiratory tract, developing an effective and convenient mucosal vaccine should be a high priority. [...] Read more.

COVID-19 and influenza both cause enormous disease burdens, and vaccines are the primary measures for their control. Since these viral diseases are transmitted through the mucosal surface of the respiratory tract, developing an effective and convenient mucosal vaccine should be a high priority. We previously reported a recombinant vesicular stomatitis virus (rVSV)-based bivalent vaccine (v-EM2/SPΔC1_Delta) that protects animals from both SARS-CoV-2 and influenza viruses via intramuscular and intranasal immunization. Here, we further investigated the immune response induced by oral immunization with this vaccine and its protective efficacy in mice. The results demonstrated that the oral delivery, like the intranasal route, elicited strong and protective systemic immune responses against SARS-CoV-2 and influenza A virus. This included high levels of neutralizing antibodies (NAbs) against SARS-CoV-2, as well as strong anti-SARS-CoV-2 spike protein (SP) antibody-dependent cellular cytotoxicity (ADCC) and anti-influenza M2 ADCC responses in mice sera. Furthermore, it provided efficient protection against challenge with influenza H1N1 virus in a mouse model, with a 100% survival rate and a significantly low lung viral load of influenza virus. All these findings provide substantial evidence for the effectiveness of oral immunization with the rVSV bivalent vaccine. Full article

(This article belongs to the Special Issue New Trends in SARS-CoV-2 Variants and Vaccines)

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19 pages, 5048 KiB

Open AccessArticle

Deep Structural Analysis of Myriads of Omicron Sub-Variants Revealed Hotspot for Vaccine Escape Immunity

by Valeria Gerardi, Mohammed A. Rohaim, Rania F. El Naggar, Mustafa O. Atasoy and Muhammad Munir

Vaccines 2023, 11(3), 668; https://doi.org/10.3390/vaccines11030668 - 15 Mar 2023

Cited by 3 | Viewed by 2057

Abstract

The emergence of the Omicron variant has reinforced the importance of continued SARS-CoV-2 evolution and its possible impact on vaccine effectiveness. Specifically, mutations in the receptor-binding domain (RBD) are critical to comprehend the flexibility and dynamicity of the viral interaction with the human [...] Read more.

The emergence of the Omicron variant has reinforced the importance of continued SARS-CoV-2 evolution and its possible impact on vaccine effectiveness. Specifically, mutations in the receptor-binding domain (RBD) are critical to comprehend the flexibility and dynamicity of the viral interaction with the human agniotensin-converting enzyme 2 (hACE2) receptor. To this end, we have applied a string of deep structural and genetic analysis tools to map the substitution patterns in the S protein of major Omicron sub-variants (n = 51) with a primary focus on the RBD mutations. This head-to-head comparison of Omicron sub-variants revealed multiple simultaneous mutations that are attributed to antibody escape, and increased affinity and binding to hACE2. Our deep mapping of the substitution matrix indicated a high level of diversity at the N-terminal and RBD domains compared with other regions of the S protein, highlighting the importance of these two domains in a matched vaccination approach. Structural mapping identified highly variable mutations in the up confirmation of the S protein and at sites that critically define the function of the S protein in the virus pathobiology. These substitutional trends offer support in tracking mutations along the evolutionary trajectories of SAR-CoV-2. Collectively, the findings highlight critical areas of mutations across the major Omicron sub-variants and propose several hotspots in the S proteins of SARS-CoV-2 sub-variants to train the future design and development of COVID-19 vaccines. Full article

(This article belongs to the Special Issue New Trends in SARS-CoV-2 Variants and Vaccines)

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19 pages, 1439 KiB

Open AccessArticle

Homologous and Heterologous Prime-Boost Vaccination: Impact on Clinical Severity of SARS-CoV-2 Omicron Infection among Hospitalized COVID-19 Patients in Belgium

by Marjan Meurisse, Lucy Catteau, Joris A. F. van Loenhout, Toon Braeye, Laurane De Mot, Ben Serrien, Koen Blot, Emilie Cauët, Herman Van Oyen, Lize Cuypers, Belgian Collaborative Group on COVID-19 Hospital Surveillance, COVID-19 Genomics Belgium Consortium, Annie Robert and Nina Van Goethem

Vaccines 2023, 11(2), 378; https://doi.org/10.3390/vaccines11020378 - 7 Feb 2023

Cited by 2 | Viewed by 2147

Abstract

We investigated effectiveness of (1) mRNA booster vaccination versus primary vaccination only and (2) heterologous (viral vector–mRNA) versus homologous (mRNA–mRNA) prime-boost vaccination against severe outcomes of BA.1, BA.2, BA.4 or BA.5 Omicron infection (confirmed by whole genome sequencing) among hospitalized COVID-19 patients using [...] Read more.

We investigated effectiveness of (1) mRNA booster vaccination versus primary vaccination only and (2) heterologous (viral vector–mRNA) versus homologous (mRNA–mRNA) prime-boost vaccination against severe outcomes of BA.1, BA.2, BA.4 or BA.5 Omicron infection (confirmed by whole genome sequencing) among hospitalized COVID-19 patients using observational data from national COVID-19 registries. In addition, it was investigated whether the difference between the heterologous and homologous prime-boost vaccination was homogenous across Omicron sub-lineages. Regression standardization (parametric g-formula) was used to estimate counterfactual risks for severe COVID-19 (combination of severity indicators), intensive care unit (ICU) admission, and in-hospital mortality under exposure to different vaccination schedules. The estimated risk for severe COVID-19 and in-hospital mortality was significantly lower with an mRNA booster vaccination as compared to only a primary vaccination schedule (RR = 0.59 [0.33; 0.85] and RR = 0.47 [0.15; 0.79], respectively). No significance difference was observed in the estimated risk for severe COVID-19, ICU admission and in-hospital mortality with a heterologous compared to a homologous prime-boost vaccination schedule, and this difference was not significantly modified by the Omicron sub-lineage. Our results support evidence that mRNA booster vaccination reduced the risk of severe COVID-19 disease during the Omicron-predominant period. Full article

(This article belongs to the Special Issue New Trends in SARS-CoV-2 Variants and Vaccines)

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11 pages, 1441 KiB

Open AccessArticle

SARS-CoV-2 Seroprevalence in Unvaccinated Adults in Thailand in November 2021

by Surakameth Mahasirimongkol, Ballang Uppapong, Wiroj Puangtubtim, Panadda Dhepakson, Parnuphan Panyajai, Naphatcha Thawong, Nadthanan Pinyosukhee, Archawin Rojanawiwat, Nuanjun Wichukchinda, Sakulrat Soonthorncharttrawat, Kanisorn Larpardisorn, Sumet Amonyingcharoen, Kritchai Juntaped, Tassanee Chaiyakum, Chayada Tongkamsen, Jeerapa Srilaket, Jiratikamon Chipatoom, Rattanawadee Wichajarn, Nutchanat Chatchawankanpanich, Lapasrada Pattarapreeyakul, Porntip Chaiya, Kaveewan Mongkolsiri, Suthida Tuntigumthon, Kritsamon Sophondilok, Nalinee Saengtong, Kodcharad Jongpitisub and Supakit Sirilak Show full author list Hide full author list

Vaccines 2022, 10(12), 2169; https://doi.org/10.3390/vaccines10122169 - 16 Dec 2022

Viewed by 1301

Abstract

Between the first case of COVID-19 in January 2020 and the end of 2021, Thailand experienced four waves of the epidemic. The third and fourth waves were caused by the alpha and delta strains from April 2021 to November 2021. Serosurveillance studies provide [...] Read more.

Between the first case of COVID-19 in January 2020 and the end of 2021, Thailand experienced four waves of the epidemic. The third and fourth waves were caused by the alpha and delta strains from April 2021 to November 2021. Serosurveillance studies provide snapshots of the true scale of the outbreak, including the asymptomatic infections that could not be fully captured by a hospital-based case detection system. We aimed to investigate the distribution of SARs-CoV-2 seroprevalence in unvaccinated adults after the delta wave outbreak. From November to December 2021, we conducted a cross-sectional survey study in 12 public health areas (PHAs) across Thailand. A total of 26,717 blood samples were collected and tested for SARs-CoV-2 antibodies (anti-S IgG) using a qualitative immunoassay. The results showed that seropositive prevalence in this cohort was 1.4% (95% CI: 1.24 to 1.52). The lowest prevalence was in the northern region (PHA 1) and in central Thailand (PHA 3) at 0.4% (95% CI: 0.15 to 0.95), while the highest was in the southern region of Thailand (PHA 12) at 5.8% (95% CI: 4.48 to 7.29). This seropositive prevalence was strikingly lower than the reports from other countries. Our serosurveillance results suggest that the vaccination of unvaccinated groups should be accelerated, especially in the public health areas with the lowest seroprevalence. Full article

(This article belongs to the Special Issue New Trends in SARS-CoV-2 Variants and Vaccines)

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Review

Jump to: Research, Other

19 pages, 1428 KiB

Open AccessReview

Significance of Conserved Regions in Coronavirus Spike Protein for Developing a Novel Vaccine against SARS-CoV-2 Infection

by Titus A. Olukitibi, Zhujun Ao, Bryce Warner, Rodrigo Unat, Darwyn Kobasa and Xiaojian Yao

Vaccines 2023, 11(3), 545; https://doi.org/10.3390/vaccines11030545 - 24 Feb 2023

Cited by 4 | Viewed by 2915

Abstract

Over the years, several distinct pathogenic coronaviruses have emerged, including the pandemic SARS-CoV-2, which is difficult to curtail despite the availability of licensed vaccines. The difficulty in managing SARS-CoV-2 is linked to changes in the variants’ proteins, especially in the spike protein (SP) [...] Read more.

Over the years, several distinct pathogenic coronaviruses have emerged, including the pandemic SARS-CoV-2, which is difficult to curtail despite the availability of licensed vaccines. The difficulty in managing SARS-CoV-2 is linked to changes in the variants’ proteins, especially in the spike protein (SP) used for viral entry. These mutations, especially in the SP, enable the virus to evade immune responses induced by natural infection or vaccination. However, some parts of the SP in the S1 subunit and the S2 subunit are considered conserved among coronaviruses. In this review, we will discuss the epitopes in the SARS-CoV-2 S1 and S2 subunit proteins that have been demonstrated by various studies to be conserved among coronaviruses and may be immunogenic for the development of a vaccine. Considering the higher conservancy of the S2, we will further discuss the likely challenges that could limit the S2 subunit from inducing robust immune responses and the promising approaches to increase its immunogenicity. Full article

(This article belongs to the Special Issue New Trends in SARS-CoV-2 Variants and Vaccines)

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Other

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14 pages, 2429 KiB

Open AccessBrief Report

Virological Traits of the SARS-CoV-2 BA.2.87.1 Lineage

by Lu Zhang, Alexandra Dopfer-Jablonka, Inga Nehlmeier, Amy Kempf, Luise Graichen, Noemí Calderón Hampel, Anne Cossmann, Metodi V. Stankov, Gema Morillas Ramos, Sebastian R. Schulz, Hans-Martin Jäck, Georg M. N. Behrens, Stefan Pöhlmann and Markus Hoffmann

Vaccines 2024, 12(5), 487; https://doi.org/10.3390/vaccines12050487 - 1 May 2024

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Abstract

Transmissibility and immune evasion of the recently emerged, highly mutated SARS-CoV-2 BA.2.87.1 are unknown. Here, we report that BA.2.87.1 efficiently enters human cells but is more sensitive to antibody-mediated neutralization than the currently dominating JN.1 variant. Acquisition of adaptive mutations might thus be [...] Read more.

Transmissibility and immune evasion of the recently emerged, highly mutated SARS-CoV-2 BA.2.87.1 are unknown. Here, we report that BA.2.87.1 efficiently enters human cells but is more sensitive to antibody-mediated neutralization than the currently dominating JN.1 variant. Acquisition of adaptive mutations might thus be needed for efficient spread in the population. Full article

(This article belongs to the Special Issue New Trends in SARS-CoV-2 Variants and Vaccines)

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