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Summary: Despite global vaccination efforts, the SARS-CoV-2 virus causing COVID-19 continues to mutate and spread. The Omicron variant, with 50 genetic mutations including 15 in the receptor-binding domain (RBD) of the spike protein, has become dominant worldwide. This study used molecular dynamics simulation and thermophoresis methods to analyze the interaction between Omicron RBD and ACE2. The results show that the Omicron variant has enhanced binding to ACE2 compared to the original strain, potentially leading to increased infectivity.
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Alexandre Nicolas et al.
Summary: Spacing the first two doses of SARS-CoV-2 mRNA vaccines beyond 3-4 weeks raises concerns about vaccine efficacy, but studies have shown that long-interval regimens induce robust antibody responses. However, their impact on B and T cell immunity is still unclear.
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Eun Kim et al.
Summary: The study evaluates the booster effect of an S1 subunit vaccine in aged mice previously primed with adenoviral vaccines. It demonstrates that a booster dose of the rS1Beta subunit vaccine, given to mice, induces strong and long-lived S1-specific immune responses and significantly increases neutralizing antibodies against Wuhan, Beta, and Delta strains, including cross-reactive antibodies against Omicron variants. The findings suggest that the rS1Beta subunit vaccine can offer cross-neutralization against broad variants, providing important implications for controlling breakthrough SARS-CoV-2 variants in elderly individuals primed with adenovirus-based vaccines.
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Summary: Older people have suboptimal responses to primary series vaccines, but booster vaccines can increase antibody levels in the short term. However, antibody levels decline within 100 days after the booster shots and breakthrough infections can still occur. This study highlights the strong immunogenicity of a third vaccine dose in vulnerable older populations and supports widespread vaccination in this group.
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Matthew A. Spinelli et al.
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Immunology
Paul Moss
Summary: T cell immunity plays a central role in controlling SARS-CoV-2 infection, with early responses correlating with protection. T cell memory provides broad recognition of viral proteins, limiting the impact of viral variants and offering protection against severe disease. Current COVID-19 vaccines elicit robust T cell responses, contributing to the prevention of hospitalization or death. Therefore, the importance of T cell immunity may have been underestimated.
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Helen Parry et al.
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Juliet R. C. Pulliam et al.
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Ariane Volkmann et al.
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Infectious Diseases
Li Guo et al.
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Suresh Kumar et al.
Summary: This study used computational tools to evaluate the infectivity, transmission, and pathogenicity of the Omicron variant and its sub-variants. The research found that the Omicron and sub-variants have multiple mutations in the receptor-binding domain, increasing their affinity for human ACE2 and potential for transmission. However, mutations in the spike protein's N-terminal domain may result in less impact on the lower respiratory tract. Some mutations in the sub-variants of Omicron seemed to restore the binding effectiveness to ACE2.
JOURNAL OF MEDICAL VIROLOGY
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Mohsen Heidary et al.
Summary: Efforts to develop a safe and efficient vaccine for COVID-19 are ongoing globally. Currently, there are 161 vaccine candidates in different clinical phases worldwide, as reported by the World Health Organization.
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Robert H. Shaw et al.
Summary: This study conducted exploratory analyses on the priming intervals of COVID-19 vaccines and found that longer intervals can reduce reactogenicity for the BNT162b2 vaccine as the second dose and enhance humoral immunogenicity in homologous priming schedules, but result in overall lower T-cell responses across all schedules. These findings support the flexibility of priming intervals in COVID-19 vaccine schedules.
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Immunology
Jinyi Tang et al.
Summary: SARS-CoV-2 mRNA vaccination induces strong immune responses in the circulation, but its effectiveness in the respiratory tract, especially against variants of concern like Omicron, is still uncertain. This study found lower neutralizing antibody responses in the respiratory tract of vaccinated individuals compared to COVID-19 convalescents, despite robust antibody responses in the blood. Vaccination also induced circulating B and T cell immunity, but these responses were absent in the respiratory tract. Mouse immunization experiments showed that systemic mRNA vaccination alone resulted in weak respiratory mucosal neutralizing antibody responses, but combining it with mucosal adenovirus-S immunization produced strong neutralizing antibody responses against both the ancestral virus and the Omicron variant. Overall, this study suggests that current COVID-19 vaccines are highly effective against severe disease, but provide limited protection against breakthrough infections, particularly by the Omicron sublineage.
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Antonio Bertoletti et al.
Summary: This review summarizes the evidence supporting the role of SARS-CoV-2-specific T cells in disease protection and analyzes the different factors that may influence the magnitude, function, and anatomical localization of these T cells, as well as their impact on protecting the host from severe COVID-19 development.
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Sebastian A. Wellford et al.
Summary: In this study, using multiple viral infection models in mice, researchers found that blood-borne antibodies were unable to protect the olfactory epithelium in the upper airway. They identified a restrictive blood-endothelial barrier that excluded circulating antibodies from the olfactory mucosa, and demonstrated that plasma cells must reside within olfactory tissue to achieve sterilizing immunity. The study has important implications for vaccinology, respiratory and CNS pathogen transmission, and B cell fate decisions.
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Medicine, General & Internal
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NEW ENGLAND JOURNAL OF MEDICINE
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Kathryn S. Hensley et al.
Summary: This study aimed to investigate the immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV (PLWH) in the Netherlands. The results showed that PLWH had lower antibody levels compared to HIV-negative controls after completion of the vaccination schedule. Additional vaccinations may be required for PLWH to achieve and maintain similar levels of protection against SARS-CoV-2 as HIV-negative controls.
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Immunology
Mallory L. L. Myers et al.
Summary: As new vaccine technologies are developed, studying traditional influenza split/subunit vaccines is important. In this study, three commercial influenza HA split/subunit vaccines were compared for their antibody responses and protection against different influenza B viruses. The results showed that one four-valent vaccine and one three-valent vaccine performed similarly in protecting against a cross-lineage influenza B challenge, while another three-valent vaccine failed to elicit a strong immune response.
FRONTIERS IN IMMUNOLOGY
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Xiuyuan Lu et al.
Summary: T cells play a crucial role in the defense against SARS-CoV-2 infection and generating immunity. CD4(+) T cells support antibody production, while CD8(+) T cells protect against infection. The role of cross-reactive T cells in SARS-CoV-2 immunity is still debated. T cell responses are less affected by the mutations of SARS-CoV-2 variants compared to antibodies.
INFLAMMATION AND REGENERATION
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Xiangchuan He et al.
Summary: The recent emergence of Hand, Foot, and Mouth Disease (HFMD) as a global public threat has prompted the development of a vaccine for control. Challenges include changes in pathogen spectrum and the need for multivalent vaccines against different serotypes. Recent advances in HFMD vaccine development aim to establish a cross-protective antibody response.
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Wilfredo F. Garcia-Beltran et al.
Summary: Severe cases of COVID-19 show increased inflammatory markers, lymphopenia, pro-inflammatory cytokines, and high antibody levels. High neutralization potency is a predictor of survival. Patient sera can neutralize different strains, indicating cross-protection from reinfection.
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Biochemistry & Molecular Biology
Guido Forni et al.
Summary: The development of vaccines has made significant progress, but still faces various challenges, including different target populations, immunological adaptability of vaccines, and production and distribution issues. To ensure equitable access, protection of diverse subjects, and immunity against viral variants, multiple vaccines may be needed in the long run.
CELL DEATH AND DIFFERENTIATION
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Yair Goldberg et al.
Summary: The immunity against the delta variant of SARS-CoV-2 waned in all age groups in Israel a few months after receiving the second dose of the vaccine, leading to an increase in infection and severe cases.
NEW ENGLAND JOURNAL OF MEDICINE
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Einav G. Levin et al.
Summary: A study in Israel revealed that waning immunity after receiving two doses of the BNT162b2 vaccine led to an increase in the incidence of SARS-CoV-2 infection. Levels of spike-binding IgG and neutralizing antibodies decreased more significantly in men, individuals aged 65 or older, and immunosuppressed individuals in a longitudinal study involving nearly 4000 healthcare workers.
NEW ENGLAND JOURNAL OF MEDICINE
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Annette B. Vogel et al.
Summary: The two vaccine candidates, BNT162b1 and BNT162b2, developed contain modified messenger RNA encoding immunogens derived from the spike glycoprotein of SARS-CoV-2. They have shown promising immune responses in mice and rhesus macaques, with ongoing phase I trials in Germany and the USA and a global phase II/III trial for BNT162b2.
Review
Immunology
Kim Tien Ng et al.
Summary: In the SARS-CoV-2 virus, the S2 subunit of the S protein holds potential as an attractive and promising target for the development of prophylactic vaccines and therapeutic agents against COVID-19, offering an important avenue for research.
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Markus Hoffmann et al.
Summary: The emerging SARS-CoV-2 variants may exhibit resistance to existing neutralizing antibodies and treatments, which could have significant implications for pandemic containment efforts.
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Eun Kim et al.
Summary: The Ad5-vectored SARS-CoV-2 vaccine candidate showed promising immunogenicity in mice following delivery via S.C. and I.N. routes, inducing robust antibody and cellular immune responses with long-lasting immunity. This supports further development of Ad-based vaccines for sustainable global immunization programs against COVID-19 and other infectious diseases.
EUROPEAN JOURNAL OF IMMUNOLOGY
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Review
Immunology
Liyana Ahmad
Summary: This article discusses the pressures leading to the emergence of new SARS-CoV-2 variants and key mutations that promote immune escape mechanisms, highlighting the potential threats to the efficacy of current COVID-19 vaccines. It cautions on the risks of reinfection, vaccine breakthrough infections, and therapeutic values.
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Prabhu S. Arunachalam et al.
Summary: This study demonstrated the effectiveness of an adjuvanted RBD-NP vaccine in inducing robust and durable neutralizing antibody responses, providing protection against SARS-CoV-2 infection, and cross-neutralizing various variants. Adjuvants such as AS03 and AS37 significantly enhanced the immunogenicity of the vaccine and have the potential to be candidates for COVID-19 vaccines.
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David S. Khoury et al.
Summary: The level of neutralizing antibodies is closely related to immune protection against COVID-19, playing a crucial role in protecting against detected infection and severe infection. Studies have shown that neutralizing titers will decline over time after vaccination, leading to decreased protection against SARS-CoV-2 infection.
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Yongjun Sui et al.
Summary: Comparing two adjuvanted subunit vaccines in rhesus macaques, the study found that both vaccines were effective in protecting against respiratory SARS-CoV-2 exposure, despite potential differences in mucosal and systemic protective mechanisms. The mucosal vaccine was shown to be safe after multiple doses, efficiently clearing the input virus from the nasal cavity, and may serve as a potent complementary boost to conventional systemic vaccines for overall better protection.
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Health Care Sciences & Services
Alberto Migliore et al.
Summary: The narrative review suggests that fractional intradermal vaccination can be an effective and efficient strategy for certain vaccines such as influenza, rabies, and hepatitis B. More research is needed for vaccines against other pathogens, but initial findings are promising. During a shortage of COVID-19 vaccines, exploring fractional dosing schemes could help save doses and achieve herd immunity quickly.
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Microbiology
Alba Grifoni et al.
Summary: This review summarizes recent studies on SARS-CoV-2 T cell epitopes, highlighting the significant correlation between epitope number and antigen size. It also presents an analysis of 1,400 different reported SARS-CoV-2 epitopes and identifies discrete immunodominant regions of the virus and more prevalently recognized epitopes.
CELL HOST & MICROBE
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Min-Seok Rha et al.
Summary: CD8(+) T cells play a protective role in the immune response against COVID-19, exhibiting activated phenotypes in patients despite a decrease in absolute numbers. The upregulation of inhibitory immune checkpoint receptors and expression of exhaustion-associated gene signatures in these cells have been reported, but the true exhaustion of CD8(+) T cells during COVID-19 remains controversial.
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Microbiology
William T. Harvey et al.
Summary: The evolution of SARS-CoV-2 has been characterized by the emergence of mutations and variants that impact virus characteristics. Manufacturers are preparing for possible updates to vaccines in response to changes in the virus population, and it is crucial to monitor genetic and antigenic changes alongside experiments to understand the impacts of mutations.
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Kristen A. Earle et al.
Summary: The study found a strong correlation between antibody titers and efficacy when assessing different COVID-19 vaccines, supporting the use of post-immunization antibody titers as the basis for establishing a correlate of protection for COVID-19 vaccines.
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Jenny E. Hernandez-Davies et al.
Summary: Combining variant antigens into a multivalent vaccine is a traditional approach to provide broad coverage against antigenically variable pathogens. The use of a potent combination adjuvant can enhance the breadth of antibody response to different HA subtypes, potentially future-proofing vaccines against newly-emerging variants.
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