INTRODUCTION: This review aims to provide evidence-based recommendations for an enhanced primary series (third dose) coronavirus disease 2019 (COVID-19) vaccination in people with rheumatic diseases (PRDs) in the local and regional context. METHODS: Literature reviews were performed regarding the necessity, efficacy, safety and strategies for enhanced primary series COVID-19 vaccination in PRDs. Recommendations were developed based on evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Evidence was synthesised by eight working group members, and the consensus was achieved by a Delphi method with nine members of an expert task force panel. RESULTS: Two graded recommendations and one ungraded position statement were developed. PRDs have impaired immunogenicity from the COVID-19 vaccine and are at an increased risk of postvaccine breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and poor clinical outcomes, compared to the general population. We strongly recommend that PRDs on immunomodulatory drugs be offered a third dose of the messenger RNA (mRNA) vaccine as part of an enhanced primary series, after the standard two-dose regimen. We conditionally recommend that the third dose of mRNA vaccine against SARS-CoV-2 be given at least 4 weeks after the second dose or as soon as possible thereafter. There is insufficient data to inform whether the third mRNA vaccine should be homologous or heterologous in PRDs. CONCLUSION These recommendations that were developed through evidence synthesis and formal consensus process provide guidance for an enhanced primary series COVID-19 vaccination in PRDs.
Humans ; COVID-19/prevention & control* ; COVID-19 Vaccines/administration & dosage* ; Rheumatic Diseases/immunology* ; Singapore ; SARS-CoV-2 ; Vaccination/methods* ; Delphi Technique ; Immunization, Secondary

All pandemic viruses have eventually adapted to human hosts so that they become more transmissible and less virulent. The XBB Omicron subvariant is rapidly becoming the dominant strain of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Singapore from October 2022 and is one of several variants circulating globally with the potential to dominate autumn/winter waves in different countries. The XBB Omicron subvariant has demonstrated increased transmissibility through an apparent propensity for immune evasion. This is to be expected in the natural evolution of a virus in a population highly vaccinated with a vaccine targeting the spike protein of the original Wuhan strain of the virus. This review explores the important implications of the rising prevalence of the SARS-CoV-2 Omicron subvariant for public health in Singapore and beyond.
Humans ; COVID-19/epidemiology* ; SARS-CoV-2 ; Singapore/epidemiology* ; Pandemics ; COVID-19 Vaccines ; Immune Evasion ; Spike Glycoprotein, Coronavirus/immunology*

OBJECTIVE: The present study aimed to evaluate the immunogenicity of BA.2 variant receptor binding domain (RBD) recombinant protein formulated with CpG 1826 plus alum dual adjuvant. METHODS: The BA.2 variant RBD (residues 308-548) fusing TT-P ₂ epitope was obtained from prokaryotic expression system, purification technology and dialysis renaturation, which was designated as Sot protein. The soluble Sot protein formulated with CpG 1826 plus alum dual adjuvant was designated as Sot/CA subunit vaccine and then the BALB/c mice were intramuscularly administrated with two doses of the Sot/CA subunit vaccine at 14-day interval (day 0 and 14). On day 28, the number of effector T lymphocytes secreting IFN-γ and IL-4 in mice spleen were determined by enzyme-linked immunospot (ELISpot) assay. The serum IgG, IgG1 and IgG2a antibodies were examined by enzyme-linked immunosorbent assay (ELISA). In addition, the level of neutralizing antibodies (NAbs) induced by Sot/CA subunit vaccine was also evaluated by the microneutralization assay. RESULTS: The high-purity soluble Sot protein with antigenicity was successfully obtained by the prokaryotic expression, protein purification and dialysis renaturation. The Sot/CA subunit vaccine induced a high level of IgG antibodies and NAbs, which were of cross-neutralizing activity against SARS-CoV-2 BA.2 and XBB.1.5 variants. Meanwhile, Sot/CA subunit vaccine also induced a high level of effector T lymphocytes secreting IFN-γ (635.00 ± 17.62) and IL-4 (279.20 ± 13.10), respectively. Combined with a decreased IgG1/IgG2a ratio in the serum, which indicating Sot/CA subunit vaccine induced a Th1-type predominant immune response. CONCLUSION The Sot protein formulated with CpG 1826 plus alum dual adjuvant showed that the excellent cellular and humoral immunogenicity, which provided a scientific basis for the development of BA.2 variant subunit vaccines and references for the adjuvant application of subunit vaccines.
Animals ; COVID-19 Vaccines/immunology* ; Alum Compounds/pharmacology* ; Mice, Inbred BALB C ; Vaccines, Subunit/immunology* ; Mice ; SARS-CoV-2/immunology* ; Oligodeoxyribonucleotides/administration & dosage* ; Female ; Adjuvants, Immunologic ; COVID-19/immunology* ; Antibodies, Viral/blood* ; Immunogenicity, Vaccine ; Spike Glycoprotein, Coronavirus/immunology* ; Antibodies, Neutralizing/blood* ; Adjuvants, Vaccine ; Immunoglobulin G/blood*

Compared with conventional vaccines, mRNA vaccines have considerable advantages in design, production, and application, especially in dealing with emerging infectious diseases. Particularly, mRNA vaccines were the first to be recommended by the World Health Organization for emergency use during the COVID-19 pandemic. A key to the design of mRNA vaccines is to ensure the stable and sufficient expression of the encoded protein in the recipient. In recent years, advances have been attained in the experimental and computational research in this area. This review focused on the progress and problems in improving the translation efficiency of mRNA vaccines in recent years, aiming to promote related research.
mRNA Vaccines ; Humans ; Protein Biosynthesis ; Vaccines, Synthetic/immunology* ; COVID-19 Vaccines/immunology* ; COVID-19/prevention & control* ; SARS-CoV-2/genetics* ; RNA, Messenger/genetics*

BACKGROUND: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines. METHODS: Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT + CD4 + and TIGIT + CD8 + T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose. RESULTS: Compared to that in HCs, the frequency of TIGIT + CD8 + T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT + CD8 + T cells also increased. A decrease in the ratio of both T naïve (T N ) and central memory (T CM ) cells among TIGIT + CD8 + T cells and an increase in the ratio of the effector memory (T EM ) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT + CD8 + T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT + CD8 + T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT + CD8 + T cells in PLWH were significantly weaker than those of TIGIT - CD8 + T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT + CD8 + T cells and TIGIT - CD8 + T cells was insignificant at 4W and 12W, except at 0W. CONCLUSIONS TIGIT expression on CD8 + T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8 + T cells, thereby enhancing the effectiveness of vaccination.
Humans ; Antibodies, Viral ; CD8-Positive T-Lymphocytes ; COVID-19/complications* ; COVID-19 Vaccines/immunology* ; HIV Infections/complications* ; Receptors, Immunologic ; SARS-CoV-2

OBJECTIVES: In this article, we aim to share our experience in the hospital reorganization made to conduct the SARS-CoV-2 vaccination campaign, based on the principles of flexibility and adaptability. STUDY DESIGN: A descriptive study. METHODS: The data concerning the organization of the vaccination campaign were taken from the operative protocol developed by the hospital dedicated task force, composed by experts in hygiene, public health, occupational medicine, pharmacists, nurses, hospital quality, and disaster managers. Data about the numbers of vaccine administered daily were collected by the Innovation and Development Operative Unit database. RESULTS: Vaccinations against COVID-19 started across the EU on the 27th of December 2020. The first phase of the vaccination campaign carried out in our hospital was directed to healthcare workers immunization including medical residents, social care operators, administrative staff and technicians, students of medicine, and health professions trainees. The second phase was enlarged to the coverage of extremely fragile subjects. Thanks to the massive employment of healthcare workers and the establishment of dynamic pathways, it was possible to achieve short turnaround times and a large number of doses administered daily, with peaks of 870 vaccines per day. From the 27th of December up to the 14th of March a total of 26,341 doses of Pfizer have been administered. 13,584 were first doses and 12,757 were second doses. From the 4th to the 14th of March, 296 first doses of Moderna were dispensed. It was necessary to implement adequate spaces and areas adopting anti-contagion safety measures: waiting area for subjects to be vaccinated, working rooms for the dilution of the vaccine and the storage of the material, vaccination rooms, post-vaccination observation areas, room for observation, and treatment of any adverse reactions, with an emergency cart available in each working area. CONCLUSIONS The teaching hospital of Pisa faced the beginning of the immunization campaign readjusting its spaces, planning an adequate hospital vaccination area and providing an organization plan to ensure the achievement of the targets of the campaign. This represented a challenge due to limited vaccine doses supplied and the multisectoral teams of professionals to coordinate in the shortest time and the safest way possible. The organizational model adopted proved to be adequate and therefore exploited also for the second phase aimed to extremely fragile subjects.
2019-nCoV Vaccine mRNA-1273 ; BNT162 Vaccine ; COVID-19/prevention & control* ; COVID-19 Vaccines/administration & dosage* ; Hospitals, Teaching/organization & administration* ; Humans ; Immunization Programs/organization & administration* ; Italy/epidemiology* ; SARS-CoV-2/immunology*

Antibodies, Neutralizing/immunology* ; Antibodies, Viral/immunology* ; COVID-19/virology* ; COVID-19 Vaccines/immunology* ; Humans ; SARS-CoV-2/pathogenicity* ; Spike Glycoprotein, Coronavirus/immunology* ; Vaccines, Inactivated/immunology*