Immune Responses to SARS-CoV-2 Infection and Vaccination

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "COVID-19 Vaccines and Vaccination".

Deadline for manuscript submissions: closed (10 July 2023) | Viewed by 18828

Special Issue Editor

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Interests: antibody response; immune evasion; cellular response; innate immunity

Special Issue Information

Dear Colleagues,

The COVID-19 pandemic has caused unprecedented health crises and economic losses worldwide. Its etiological agent, SARS-CoV-2, a new virus in the coronavirus family, has infected hundreds of millions of people in the past 2 years. The SARS-CoV-2 variants evolved with escape mutations and have led to the occurrence of several COVID-19 surge peaks in the past. While the virus continues to evolve with escape mutations, understanding the immune response and antigen recognition to SARS-CoV-2 variants are urgently needed for next-generation vaccine design.

This Special Issue aims to understand viral entry mechanisms, immune responses, and antigen recognition in the context of SARS-CoV-2 variants and how broad-spectrum immunity can be archived with current knowledge. We are hoping this Special Issue provides information on developing antibody therapeutics and next-generation vaccine design, which will likely prevent SARS-CoV-2 transmission and stop the COVID-19 pandemic.

We are pleased to invite you to present your latest research, perspectives, communications, and reviews to this Special Issue. All immune-related themes regarding SARS-CoV-2 and other related coronaviruses will be considered. However, we are particularly interested in understanding adaptive immune responses to SARS-CoV-2 infection, vaccination, and other related coronaviruses.

I look forward to receiving your contributions to ending this unprecedented pandemic.

Dr. Hejun Liu
Guest Editor

Manuscript Submission Information

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Keywords

  • immune response
  • antibody
  • SARS-CoV-2
  • variant
  • escape mutation
  • vaccine

Published Papers (9 papers)

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Research

Jump to: Review

16 pages, 1937 KiB  
Article
Sex Differences and Cytokine Profiles among Patients Hospitalized for COVID-19 and during Their Recovery: The Predominance of Adhesion Molecules in Females and Oxidative Stress in Males
by Olivera Mitrović-Ajtić, Dragoslava Đikić, Tijana Subotički, Sandra Bižić-Radulović, Bojana Beleslin-Čokić, Teodora Dragojević, Emilija Živković, Sanja Miljatović, Milica Vukotić, Dejana Stanisavljević, Juan Santibanez and Vladan P. Čokić
Vaccines 2023, 11(10), 1560; https://doi.org/10.3390/vaccines11101560 - 03 Oct 2023
Viewed by 1225
Abstract
The severity and mortality of coronavirus disease 2019 (COVID-19) are greater in males than in females, though the infection rate is the same in the two sexes. We investigated sex hormone differences associated with the hyperinflammatory immune response to SARS-CoV-2 on the basis [...] Read more.
The severity and mortality of coronavirus disease 2019 (COVID-19) are greater in males than in females, though the infection rate is the same in the two sexes. We investigated sex hormone differences associated with the hyperinflammatory immune response to SARS-CoV-2 on the basis of patients’ cytokine profiles and vaccination statuses. Clinical and laboratory data of 117 patients with COVID-19 were collected to examine sex differences associated with oxidative stress markers, neutrophil extracellular traps (NETs), and plasma cytokine levels up to 5 months from hospital admission. The testosterone and free testosterone levels were low in male patients with COVID-19 and returned to normal values after recovery from the disease. The dihydrotestosterone (DHT) levels were transiently reduced, while the sex hormone-binding globulin levels were decreased in post-COVID-19 male patients. The levels of the inflammatory cytokines interleukin-6 (IL-6) and IL-10 appeared generally increased at diagnosis and decreased in post-COVID-19 patients. In females, the concentration of tumor necrosis factor-alpha was increased by four times at diagnosis. The levels of the coagulation markers intercellular adhesion molecule-1 (ICAM-1) and E-selectin were consistently upregulated in post-COVID-19 female patients, in contrast to those of vascular cell adhesion molecule-1 (VCAM-1), P-selectin, and chemokine IL-8. DHT increased the levels of reactive oxygen species in the neutrophils of male patients, while estradiol decreased them in females. Markers for NET, such as circulating DNA and myeloperoxidase, were significantly more abundant in the patients’ plasma. Sex hormones have a potential protective role during SARS-CoV-2 infection, which is weakened by impaired testosterone synthesis in men. Full article
(This article belongs to the Special Issue Immune Responses to SARS-CoV-2 Infection and Vaccination)
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11 pages, 1642 KiB  
Article
Neutralizing Activity against BQ.1.1, BN.1, and XBB.1 in Bivalent COVID-19 Vaccine Recipients: Comparison by the Types of Prior Infection and Vaccine Formulations
by Hak-Jun Hyun, Min-Joo Choi, Eliel Nham, Hye Seong, Jin-Gu Yoon, Ji-Yun Noh, Hee-Jin Cheong, Woo-Joo Kim, Sun-Kyung Yoon, Se-Jin Park, Won-Seok Gwak, June-Woo Lee, Byoung-Guk Kim and Joon-Young Song
Vaccines 2023, 11(8), 1320; https://doi.org/10.3390/vaccines11081320 - 04 Aug 2023
Viewed by 1260
Abstract
Bivalent COVID-19 vaccines that contain BA.1 or BA.4/BA.5 have been introduced worldwide in response to pandemic waves of Omicron subvariants. This prospective cohort study was aimed to compare neutralizing antibodies (Nabs) against Omicron subvariants (BA.1, BA.5, BQ.1.1, BN.1, and XBB.1) before and 3–4 [...] Read more.
Bivalent COVID-19 vaccines that contain BA.1 or BA.4/BA.5 have been introduced worldwide in response to pandemic waves of Omicron subvariants. This prospective cohort study was aimed to compare neutralizing antibodies (Nabs) against Omicron subvariants (BA.1, BA.5, BQ.1.1, BN.1, and XBB.1) before and 3–4 weeks after bivalent booster by the types of SARS-CoV-2 variants in prior infections and bivalent vaccine formulations. A total of 21 participants were included. Prior BA.1/BA.2-infected, and BA.5-infected participants showed significantly higher geometric mean titers of Nab compared to SARS-CoV-2-non-infected participants after bivalent booster (BA.1, 8156 vs. 4861 vs. 1636; BA.5, 6515 vs. 4861 vs. 915; BQ.1.1, 697 vs. 628 vs. 115; BN.1, 1402 vs. 1289 vs. 490; XBB.1, 434 vs. 355 vs. 144). When compared by bivalent vaccine formulations, Nab titers against studied subvariants after bivalent booster did not differ between BA.1 and BA.4/BA.5 bivalent vaccine (BA.1, 4886 vs. 5285; BA.5, 3320 vs. 4118; BQ.1.1, 311 vs. 572; BN.1, 1028 vs. 1095; XBB.1, 262 vs. 362). Both BA.1 and BA.4/BA.5 bivalent vaccines are immunogenic and provide enhanced neutralizing activities against Omicron subvariants. However, even after the bivalent booster, neutralizing activities against the later Omicron strains (BQ.1.1, BN.1, and XBB.1) would be insufficient to provide protection. Full article
(This article belongs to the Special Issue Immune Responses to SARS-CoV-2 Infection and Vaccination)
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17 pages, 2572 KiB  
Article
Combination of Recombinant Proteins S1/N and RBD/N as Potential Vaccine Candidates
by Noe Juvenal Mendoza-Ramírez, Julio García-Cordero, Sandra Paola Martínez-Frías, Daniela Roa-Velázquez, Rosendo Luria-Pérez, José Bustos-Arriaga, Jesús Hernández-Lopez, Carlos Cabello-Gutiérrez, Joaquín Alejandro Zúñiga-Ramos, Edgar Morales-Ríos, Sonia Mayra Pérez-Tapia, Martha Espinosa-Cantellano and Leticia Cedillo-Barrón
Vaccines 2023, 11(4), 864; https://doi.org/10.3390/vaccines11040864 - 18 Apr 2023
Viewed by 1972
Abstract
Despite all successful efforts to develop a COVID-19 vaccine, the need to evaluate alternative antigens to produce next-generation vaccines is imperative to target emerging variants. Thus, the second generation of COVID-19 vaccines employ more than one antigen from severe acute respiratory syndrome coronavirus [...] Read more.
Despite all successful efforts to develop a COVID-19 vaccine, the need to evaluate alternative antigens to produce next-generation vaccines is imperative to target emerging variants. Thus, the second generation of COVID-19 vaccines employ more than one antigen from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to induce an effective and lasting immune response. Here, we analyzed the combination of two SARS-CoV-2 viral antigens that could elicit a more durable immune response in both T- and B-cells. The nucleocapsid (N) protein, Spike protein S1 domain, and receptor binding domain (RBD) of the SARS-CoV-2 spike surface glycoproteins were expressed and purified in a mammalian expression system, taking into consideration the posttranscriptional modifications and structural characteristics. The immunogenicity of these combined proteins was evaluated in a murine model. Immunization combining S1 or RBD with the N protein induced higher levels of IgG antibodies, increased the percentage of neutralization, and elevated the production of cytokines TNF-α, IFN-γ, and IL-2 compared to the administration of a single antigen. Furthermore, sera from immunized mice recognized alpha and beta variants of SARS-CoV-2, which supports ongoing clinical results on partial protection in vaccinated populations, despite mutations. This study identifies potential antigens for second-generation COVID-19 vaccines. Full article
(This article belongs to the Special Issue Immune Responses to SARS-CoV-2 Infection and Vaccination)
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13 pages, 2439 KiB  
Article
Potent NTD-Targeting Neutralizing Antibodies against SARS-CoV-2 Selected from a Synthetic Immune System
by Wenping Li, Fulian Wang, Yu Li, Lei Yan, Lili Liu, Wei Zhu, Peixiang Ma, Xiaojie Shi and Guang Yang
Vaccines 2023, 11(4), 771; https://doi.org/10.3390/vaccines11040771 - 31 Mar 2023
Cited by 4 | Viewed by 1443
Abstract
The majority of neutralizing antibodies (NAbs) against SARS-CoV-2 recognize the receptor-binding domain (RBD) of the spike (S) protein. As an escaping strategy, the RBD of the virus is highly variable, evolving mutations to thwart a natural immune response or vaccination. Targeting non-RBD regions [...] Read more.
The majority of neutralizing antibodies (NAbs) against SARS-CoV-2 recognize the receptor-binding domain (RBD) of the spike (S) protein. As an escaping strategy, the RBD of the virus is highly variable, evolving mutations to thwart a natural immune response or vaccination. Targeting non-RBD regions of the S protein thus provides a viable alternative to generating potential, robust NAbs. Using a pre-pandemic combinatorial antibody library of 1011, through an alternate negative and positive screening strategy, 11 non-RBD-targeting antibodies are identified. Amongst one NAb that binds specifically to the N-terminal domain of the S protein, SA3, shows mutually non-exclusive binding of the angiotensin-converting enzyme 2 receptor with the S protein. SA3 appears to be insensitive to the conformational change and to interact with both the “open” and “closed” configurations of the trimeric S protein. SA3 shows compatible neutralization as S-E6, an RBD-targeting NAb, against the wild type and variant of concern (VOC) B.1.351 (Beta) of the SARS-CoV-2 pseudo virus. More importantly, the combination of SA3 with S-E6 is synergistic and recovers from the 10-fold loss in neutralization efficacy against the VOC B.1.351 pseudo virus. Full article
(This article belongs to the Special Issue Immune Responses to SARS-CoV-2 Infection and Vaccination)
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15 pages, 1119 KiB  
Article
T-Cell Response and Antibody Production Induced by the COVID-19 Booster Vaccine in Japanese Chronic Kidney Disease Patients Treated with Hemodialysis
by Ayumi Yoshifuji, Masataro Toda, Munekazu Ryuzaki, Emi Oyama, Kan Kikuchi, Toru Kawai, Ken Sakai, Masayoshi Koinuma, Kazuhiko Katayama, Takashi Yokoyama, Yuki Uehara, Norio Ohmagari, Yoshihiko Kanno, Hirofumi Kon, Toshio Shinoda, Yaoko Takano, Junko Tanaka, Kazuhiko Hora, Yasushi Nakazawa, Naoki Hasegawa, Norio Hanafusa, Fumihiko Hinoshita, Keita Morikane, Shu Wakino, Hidetomo Nakamoto and Yoshiaki Takemotoadd Show full author list remove Hide full author list
Vaccines 2023, 11(3), 653; https://doi.org/10.3390/vaccines11030653 - 14 Mar 2023
Cited by 5 | Viewed by 1356
Abstract
Humoral and cellular responses are critical in understanding immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Here, we evaluated these responses in hemodialysis (HD) patients after the booster vaccination. SARS-CoV-2 immunoglobulin (IgG) levels, neutralizing antibody titers, and the T-SPOT® [...] Read more.
Humoral and cellular responses are critical in understanding immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Here, we evaluated these responses in hemodialysis (HD) patients after the booster vaccination. SARS-CoV-2 immunoglobulin (IgG) levels, neutralizing antibody titers, and the T-SPOT®.COVID test (T-SPOT) were measured prior to, three weeks after, and three months after the booster administration. The HD group had significantly higher SARS-CoV-2 IgG levels and neutralizing antibody titers against the original strain at three weeks and three months after the booster vaccination compared to the control group, albeit the HD group had lower SARS-CoV-2 IgG levels and neutralizing antibody titers before the booster administration. Moreover, the HD group had significantly higher T-SPOT levels at all three time points compared to the control group. The HD group also had significantly higher local and systemic adverse reaction rates than the control group. By booster vaccination, HD patients could acquire more effective SARS-CoV-2-specific humoral and cellular immunity than the control group. Full article
(This article belongs to the Special Issue Immune Responses to SARS-CoV-2 Infection and Vaccination)
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14 pages, 1344 KiB  
Article
Near-Complete SARS-CoV-2 Seroprevalence among Rural and Urban Kenyans despite Significant Vaccine Hesitancy and Refusal
by Carolyne Nasimiyu, Isaac Ngere, Jeanette Dawa, Patrick Amoth, Ouma Oluga, Carol Ngunu, Harriet Mirieri, John Gachohi, Moshe Dayan, Nzisa Liku, Ruth Njoroge, Raymond Odinoh, Samuel Owaka, Samoel A. Khamadi, Samson L. Konongoi, Sudi Galo, Linet Elamenya, Marianne Mureithi, Omu Anzala, Robert Breiman, Eric Osoro and M. Kariuki Njengaadd Show full author list remove Hide full author list
Vaccines 2023, 11(1), 68; https://doi.org/10.3390/vaccines11010068 - 28 Dec 2022
Cited by 4 | Viewed by 1628
Abstract
Considering the early inequity in global COVID-19 vaccine distribution, we compared the level of population immunity to SARS-CoV-2 with vaccine uptake and refusal between rural and urban Kenya two years after the pandemic onset. A population-based seroprevalence study was conducted in the city [...] Read more.
Considering the early inequity in global COVID-19 vaccine distribution, we compared the level of population immunity to SARS-CoV-2 with vaccine uptake and refusal between rural and urban Kenya two years after the pandemic onset. A population-based seroprevalence study was conducted in the city of Nairobi (n = 781) and a rural western county (n = 810) between January and February 2022. The overall SARS-CoV-2 seroprevalence was 90.2% (95% CI, 88.6–91.2%), including 96.7% (95% CI, 95.2–97.9%) among urban and 83.6% (95% CI, 80.6–86.0%) among rural populations. A comparison of immunity profiles showed that >50% of the rural population were strongly immunoreactive compared to <20% of the urban population, suggesting more recent infections or vaccinations in the rural population. More than 45% of the vaccine-eligible (≥18 years old) persons had not taken a single dose of the vaccine (hesitancy), including 47.6% and 46.9% of urban and rural participants, respectively. Vaccine refusal was reported in 19.6% of urban and 15.6% of rural participants, attributed to concern about vaccine safety (>75%), inadequate information (26%), and concern about vaccine effectiveness (9%). Less than 2% of vaccine refusers cited religious or cultural beliefs. These findings indicate that despite vaccine inequity, hesitancy, and refusal, herd immunity had been achieved in Kenya and likely other African countries by early 2022, with natural infections likely contributing to most of this immunity. However, vaccine campaigns should be sustained due to the need for repeat boosters associated with waning of SARS-CoV-2 immunity and emergence of immune-evading virus variants. Full article
(This article belongs to the Special Issue Immune Responses to SARS-CoV-2 Infection and Vaccination)
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Review

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15 pages, 1176 KiB  
Review
Cellular and Molecular Mechanisms of Pathogenic and Protective Immune Responses to SARS-CoV-2 and Implications of COVID-19 Vaccines
by Sheikh Mohammad Fazle Akbar, Mamun Al Mahtab and Sakirul Khan
Vaccines 2023, 11(3), 615; https://doi.org/10.3390/vaccines11030615 - 08 Mar 2023
Cited by 2 | Viewed by 1685
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has devastated the world with coronavirus disease 2019 (COVID-19), which has imparted a toll of at least 631 million reported cases with 6.57 million reported deaths. In order to handle this pandemic, vaccines against SARS-CoV-2 [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has devastated the world with coronavirus disease 2019 (COVID-19), which has imparted a toll of at least 631 million reported cases with 6.57 million reported deaths. In order to handle this pandemic, vaccines against SARS-CoV-2 have been developed and billions of doses of various vaccines have been administered. In the meantime, several antiviral drugs and other treatment modalities have been developed to treat COVID-19 patients. At the end of the day, it seems that anti-SARS-CoV-2 vaccines and newly developed antiviral drugs may be improved based on various new developments. COVID-19 represents a virus-induced, immune-mediated pathological process. The severity of the disease is related to the nature and properties of the host immune responses. In addition, host immunity plays a dominant role in regulating the extent of COVID-19. The present reality regarding the role of anti-SARS-CoV-2 vaccines, persistence of SARS-CoV-2 infection even three years after the initiation of the pandemic, and divergent faces of COVID-19 have initiated several queries among huge populations, policy makers, general physicians, and scientific communities. The present review aims to provide some information regarding the molecular and cellular mechanisms underlying SARS-CoV-2 infection. Full article
(This article belongs to the Special Issue Immune Responses to SARS-CoV-2 Infection and Vaccination)
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15 pages, 840 KiB  
Review
Molecular Determinants of the Early Life Immune Response to COVID-19 Infection and Immunization
by Elisabeth M. S. Beijnen, Oludare A. Odumade and Simon D. van Haren
Vaccines 2023, 11(3), 509; https://doi.org/10.3390/vaccines11030509 - 22 Feb 2023
Cited by 1 | Viewed by 1415
Abstract
Clinical manifestations from primary COVID infection in children are generally less severe as compared to adults, and severe pediatric cases occur predominantly in children with underlying medical conditions. However, despite the lower incidence of disease severity, the burden of COVID-19 in children is [...] Read more.
Clinical manifestations from primary COVID infection in children are generally less severe as compared to adults, and severe pediatric cases occur predominantly in children with underlying medical conditions. However, despite the lower incidence of disease severity, the burden of COVID-19 in children is not negligible. Throughout the course of the pandemic, the case incidence in children has substantially increased, with estimated cumulative rates of SARS-CoV-2 infection and COVID-19 symptomatic illness in children comparable to those in adults. Vaccination is a key approach to enhance immunogenicity and protection against SARS-CoV-2. Although the immune system of children is functionally distinct from that of other age groups, vaccine development specific for the pediatric population has mostly been limited to dose-titration of formulations that were developed primarily for adults. In this review, we summarize the literature pertaining to age-specific differences in COVID-19 pathogenesis and clinical manifestation. In addition, we review molecular distinctions in how the early life immune system responds to infection and vaccination. Finally, we discuss recent advances in development of pediatric COVID-19 vaccines and provide future directions for basic and translational research in this area. Full article
(This article belongs to the Special Issue Immune Responses to SARS-CoV-2 Infection and Vaccination)
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17 pages, 1040 KiB  
Review
The Vaccine World of COVID-19: India’s Contribution
by Vivek P. Chavda, Disha R. Vihol, Hetvi K. Solanki and Vasso Apostolopoulos
Vaccines 2022, 10(11), 1943; https://doi.org/10.3390/vaccines10111943 - 17 Nov 2022
Cited by 8 | Viewed by 5492
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) eruption has left not only illness and mortality in its wake, but also an overwhelming threat to health policy, human regality, food security, and struggle worldwide. The accessibility and potential distribution of a protective and [...] Read more.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) eruption has left not only illness and mortality in its wake, but also an overwhelming threat to health policy, human regality, food security, and struggle worldwide. The accessibility and potential distribution of a protective and successful vaccination to communities throughout the world are being considered now not just, as a potential of overcoming these hurdles, but also as an example of human perseverance in the face of catastrophe. A vaccine is the only tool that can efficaciously deal with the COVID-19 catastrophe. Currently, more than 47 vaccines are permitted for emergency use in distinct parts of the world. India will play a significant role in the development of the high-priced Moderna shots and Pfizer Inc, therefore assisting in the immunization of a large portion of the world. Moreover, many of the internationally researched and developed vaccine laboratories seek manufacturing in Indian firms and companies for efficient and low-cost production of vaccines intending to provide to the world, hence, making India, a major role player during these pandemic times. This review highlights the Indian contribution to the globe for COVID-19 management. Full article
(This article belongs to the Special Issue Immune Responses to SARS-CoV-2 Infection and Vaccination)
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