Effects of the induction of humoral and cellular immunity by third vaccination for SARS-CoV-2.

To control the spread of severe disease caused by mutant strains of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), it is necessary to determine whether continued vaccination enhances humoral and cellular immunity. In this study, we examined the changes in humoral and cellular immunity to SARS-CoV-2 after administration of the third vaccination in Japanese adults who had received the second dose of messenger ribonucleic acid (mRNA)-1273 vaccine and the third vaccination (BNT162b2 or mRNA-1273). We measured anti-spike antibodies in immunoglobulin G (IgG) and anti-nucleocapsid IgG titers in the serum of the vaccinated subjects. To evaluate cellular immunity, the peripheral blood mononuclear cells of inoculated individuals were cultured with spiked proteins, including those of the SARS-CoV-2 conventional strain and Omicron strain, and then subjected to enzyme-linked immunospot (ELISPOT). The results revealed that the anti-SARS-CoV-2 spike protein antibody titer increased after the third vaccination and was maintained; however, a decrease was observed at 6 months after vaccination. SARS-CoV-2 antigen-specific T helper (Th)1 and Th2 cell responses were also induced after the third vaccination and were maintained for 6 months after vaccination. Furthermore, induction of cellular immunity against Omicron strains by the omicron non-compliant vaccines, BNT162b2 or mRNA-1273, was observed. These findings demonstrate the effectiveness of vaccination against unknown mutant strains that may occur in the future and provide important insights into vaccination strategies.

Murayama G ，Kusaoi M ，Horiuchi Y ，Tabe Y ，Naito T ，Ito S ，Yamaji K ，Tamura N ... -  《-》

Heterologous and homologous COVID-19 mRNA vaccination schemes for induction of basic immunity show similar immunogenicity regarding long-term spike-specific cellular immunity in healthcare workers.

Healthcare workers (HCWs) are recommended to receive at least three spike-antigen exposures to generate basic immunity and to mediate herd protection of vulnerable patients. So far, less attention has been put on the cellular immune response induced by homologous (three BTN162b2mRNA doses) or heterologous (mRNA-1273 as third dose building on two BTN162bmRNA doses) and the immunological impact of breakthrough infections (BTIs). Therefore, in 356 vaccinated HCWs with or without BTIs the Anti-SARS-CoV-2-Spike-IgG concentrations and avidities and B- and T-cell-reactivity against SARS-CoV-2-Spike-S1- and Nucleocapsid-antigens were assessed with Interferon-gamma-ELISpot and by flow-cytometry. HCWs who had hybrid immunity due to BTIs exhibited strong T-cell-reactivity against the Spike-S1-antigen. A lasso regression model revealed a significant reduction in T-cell immune responses among smokers (p < 0.0001), with less significant impact observed for age, sex, heterologous vaccination, body-mass-index, Anti-Nucleocapsid T-cell reactivity, days since last COVID-19-immunization, and Anti-SARS-CoV-2-Spike-IgG. Although subgroup analysis revealed higher Anti-SARS-CoV-2-Spike-IgG after heterologous vaccination, similar cellular reactivity and percentages of Spike-reactive T- and B-cells were found between homologous and heterologous vaccination. Anti-SARS-CoV-2-Spike-IgG concentrations and avidity significantly correlated with activated T-cells. CD4 + and CD8 + responses correlated with each other. A strong long-term cellular immune response should be considered as baseline for recommendations of booster doses in HCWs with prioritization of smokers. HCWs presented significant T-cellular reactivity towards Spike-S1-antigen with particularly strong responses in hybrid immunized HCWs who had BTIs. HCWs without BTI presented similar percentages of Spike-specific B- and T-cells between homologous or heterologous vaccination indicating similar immunogenicity for both mRNA vaccines, BNT162b2mRNA and mRNA-1273.

Wagenhäuser I ，Almanzar G ，Förg FB ，Stein A ，Eiter I ，Reusch J ，Mees J ，Herzog A ，Vogel U ，Frey A ，Lâm TT ，Schubert-Unkmeir A ，Dölken L ，Kurzai O ，Frantz S ，Gabel A ，Petri N ，Prelog M ，Krone M ... -  《-》

Effectiveness and evolution of anti-SARS-CoV-2 spike protein titers after three doses of COVID-19 vaccination in people with HIV.

Real-world vaccine effectiveness following the third dose of vaccination against SARS-CoV-2 remains less investigated among people with HIV (PWH). PWH receiving the third dose of BNT162b2 and mRNA-1273 (either 50- or 100-μg) were enrolled. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, SARS-CoV-2 infection, seroconversion of anti-nucleocapsid IgG, death, or loss to follow-up. Anti-spike IgG was determined every 1-3 months. Of 1427 participants undergoing the third-dose COVID-19 vaccination, 632 (44.3%) received 100-μg mRNA-1273, 467 (32.8%) 50-μg mRNA-1273, and 328 (23.0%) BNT162b2 vaccine and the respective rate of SARS-CoV-2 infection or seroconversion of anti-nucleocapsid IgG was 246.1, 280.8 and 245.2 per 1000 person-months of follow-up (log-rank test, p = 0.28). Factors associated with achieving anti-S IgG titers >1047 BAU/mL included CD4 count <200 cells/mm3 (adjusted odds ratio [aOR], 0.11; 95% CI, 0.04-0.31), plasma HIV RNA >200 copies/mL (aOR, 0.27; 95% CI, 0.09-0.80), having achieved anti-spike IgG >141 BAU/mL within 3 months after primary vaccination (aOR, 3.69; 95% CI, 2.68-5.07), receiving BNT162b2 vaccine as the third dose (aOR, 0.20; 95% CI, 0.10-0.41; reference, 100-μg mRNA-1273), and having previously received two doses of mRNA vaccine in primary vaccination (aOR, 2.46; 95% CI, 1,75-3.45; reference, no exposure to mRNA vaccine). PWH receiving different types of the third dose of COVID-19 vaccine showed similar vaccine effectiveness against SARS-CoV-2 infection. An additional dose with 100-μg mRNA-1273 could generate a higher antibody response than with 50-μg mRNA-1273 and BNT162b2 vaccine.

Liu WD ，Lin MS ，Sun HY ，Shih MC ，Chuang YC ，Huang YS ，Lin KY ，Li GC ，Wu PY ，Chen LY ，Liu WC ，Su YC ，He PC ，Chen YT ，Lin CY ，Cheng YC ，Yao Y ，Yeh YC ，Liu CC ，Pan MY ，Luo YZ ，Chang HY ，Wang JT ，Sheng WH ，Hsieh SM ，Chang SY ，Hung CC ... -  《-》

Antigen-specific T helper cells and cytokine profiles predict intensity and longevity of cellular and humoral responses to SARS-CoV-2 booster vaccination.

Page L ，Dennehy K ，Mueller K ，Girl P ，Loell E ，Buijze H ，Classen JM ，Messmann H ，Roemmele C ，Hoffmann R ，Wurster S ，Fuchs A ... -  《Frontiers in Immunology》

First SARS-CoV-2 Omicron infection as an effective immune booster among mRNA vaccinated individuals: final results from the first phase of the PRIBIVAC randomised clinical trial.

Understanding how SARS-CoV-2 breakthrough infections impacts the breadth of immune responses against existing and pre-emergent SARS-CoV-2 strains is needed to develop an evidence-based long-term immunisation strategy. We performed a randomised, controlled trial to assess the immunogenicity of homologous (BNT162b2) versus heterologous (mRNA-1273) booster vaccination in 100 BNT162b2-vaccinated infection-naïve individuals enrolled from October 2021. Post hoc analysis was performed to assess the impact of SARS-CoV-2 infection on humoral and cellular immune responses against wild-type SARS-CoV-2 and/or Omicron subvariants. 93 participants completed the study at day 360. 71% (66/93) of participants reported first SARS-CoV-2 Omicron infection by the end of the study with similar proportions of infections between homologous and heterologous booster groups (72.3% [34/47] vs 69.6% [32/46]; p = 0.82). Mean wildtype SARS-CoV-2 anti-S-RBD antibody level was significantly higher in heterologous booster group compared with homologous group at day 180 (14,588 IU/mL; 95% CI, 10,186-20,893 vs 7447 IU/mL; 4646-11,912; p = 0.025). Participants who experienced breakthrough infections during the Omicron BA.1/2 wave had significantly higher anti-S-RBD antibody levels against wildtype SARS-CoV-2 and antibody neutralisation against BA.1 and pre-emergent BA.5 compared with infection-naïve participants. Regardless of hybrid immunity status, wildtype SARS-CoV-2 anti-S-RBD antibody level declined significantly after six months post-booster or post-SARS-CoV-2 infection. Booster vaccination with mRNA-1273 was associated with significantly higher antibody levels compared with BNT162b2. Antibody responses are narrower and decline faster among uninfected, vaccinated individuals. Boosters may be more effective if administered shortly before infection outbreaks and at least six months after last infection or booster. Singapore NMRC, USFDA, MRC.

Poh XY ，Lee IR ，Tan CW ，Chavatte JM ，Fong SW ，Goh YS ，Rouers A ，Wong N ，Torres-Ruesta A ，Mah SYY ，Yeoh AYY ，Gandhi M ，Rahman N ，Chin YQ ，Lim JJ ，Yoong TJK ，Rao S ，Chia PY ，Ong SWX ，Lee TH ，Sadarangani SP ，Lin RJH ，Lim DRX ，Chia W ，Renia L ，Ren EC ，Lin RTP ，Lye DC ，Wang LF ，Ng LFP ，Young BE ... -  《EBioMedicine》