Immunogenicity of BNT162b2 and CoronaVac boosters in fully vaccinated individuals with CoronaVac against SARS-CoV-2: A Longitudinal Study

Objective: There is a need for the immunogenicity of different boosters after widely used inactivated vaccine regimens. We aimed to determine the effects of BNT162b2 and CoronaVac boosters on the humoral and cellular immunity of individuals who had two doses of CoronaVac vaccination. Methods: The study was conducted in three centers (Koc University Hospital, Istanbul University Cerrahpasa Hospital, and Istanbul University, Istanbul Medical School Hospital) in Istanbul. Individuals who had two doses of CoronaVac and no history of COVID-19 were included. The baseline blood samples were collected three to five months after two doses of CoronaVac. Follow-up samples were taken one and three months after third doses of CoronaVac or one dose of mRNA BNT162b2 boosters. Neutralizing antibody titers were detected by plaque reduction assay. T cell responses were evaluated by Elispot assay and flow cytometry. Results: We found a 3.38-fold increase in neutralizing antibody titers (Geometric Mean Titer [GMT], 78.69) one month after BNT162b2 booster and maintained at the three months (GMT, 80). However, in the CoronaVac group, significantly lower GMTs than BNT162b2 after 1 month and 3 months (21.44 and 28.44, respectively) indicated the weak immunogenicity of the CoronaVac booster (p<0.001). In the ELISpot assay, IL-2 levels after BNT162b2 were higher than baseline and CoronaVac booster (p<0.001) and IFN-γ levels were significantly higher than baseline (P<0.001). The CD8+CD38+CD69+ and CD4+CD38+CD69+ T cells were stimulated significantly at the 3 month of the BNT162b2 boosters. Conclusion: The neutralizing antibody levels after three months of the BNT162b2 booster were higher than the antibody levels after CoronaVac. On the other hand, specific T cells might contribute to immune protection. By considering the waning immunity, we suggest a new booster dose with BNT162b2 for the countries that already have two doses of primary CoronaVac regimens.

Zika virus baculovirus-expressed envelope protein elicited humoral and cellular immunity in immunocompetent mice

Zika virus (ZIKV) is a mosquito-borne virus that has a high risk of inducing Guillain–Barré syndrome and microcephaly in newborns. Because vaccination is considered the most effective strategy against ZIKV infection, we designed a recombinant vaccine utilizing the baculovirus expression system with two strains of ZIKV envelope protein (MR766, Env_M; ZBRX6, Env_Z). Animals inoculated with Env_M and Env_Z produced ZIKV-specific antibodies and secreted effector cytokines such as interferon-γ, tumor necrosis factor-α, and interleukin-12. Moreover, the progeny of immunized females had detectable maternal antibodies that protected them against two ZIKV strains (MR766 and PRVABC59) and a Dengue virus strain. We propose that the baculovirus expression system ZIKV envelope protein recombinant provides a safe and effective vaccine strategy.

Temporary hold of mycophenolate boosts SARS-CoV-2 vaccination-specific humoral and cellular immunity in kidney transplant recipients

Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from autoimmune patients suggest that temporary MPA hold might significantly improve booster vaccination outcomes. We applied a fourth dose of SARS-CoV-2 vaccine during temporary (5 weeks) MPA hold to 29 kidney transplant recipients, who had not mounted a humoral immune-response to previous vaccinations. Seroconversion until day 32 after vaccination was observed in 76% of patients, associated with acquisition of virus neutralizing capacity. Interestingly, 21/25 (84%) CNI-treated patients responded, but only 1/4 Belatacept-treated patients. In line with humoral responses, counts and relative frequencies of spike receptor binding domain (RBD) specific B cells were significantly increased on day 7 after vaccination, with an increase in RBD specific CD27++CD38+ plasmablasts. Whereas overall proportions of spike-reactive CD4+ T cells remained unaltered after the fourth dose, frequencies were positively correlated with specific IgG levels. Importantly, antigen-specific proliferating Ki67+ and in vivo activated PD1+ T cells significantly increased after re-vaccination during MPA hold, whereas cytokine production and memory differentiation remained unaffected. In summary, MPA hold was safe and augmented all arms of immunity during booster vaccination, suggesting its implementation in vaccination protocols for clinically stable transplant recipients.

Effect of Long-Acting Selenium Preparation on Health and Productivity of Sheep

The aim of this study was to determine the effects of long-acting selenium (Se) preparation in sheep. The experimental material comprised Skudda ewes and their lambs. The animals were divided into two equal groups: C-control, and E-experimental. Between days 70 and 80 of pregnancy, group E ewes were injected with Se preparation (Barium Selenate Injection, BVP Animal Care, Ireland) at f 1 mL/50 kg body weight. Hematological, biochemical and immunological blood parameters as well as Se levels were analyzed in ewes. The growth rate of lambs, the dimensions of the musculus longissimus dorsi (MLD) cross-section, and fat thickness over the loin-eye area were also determined. It was found that barium selenate stimulated the mechanisms of humoral and cellular immunity. The injection was an effective form of Se supply, which was confirmed by its increased concentration in the blood serum of lactating ewes. The offspring of the experimental ewes were characterized by a faster growth rate, and they achieved significantly higher body weight (p ≤ 0.05) at 100 days of age. The lambs also had significantly higher parameters of MLD (p ≤ 0.05) at similar carcass fat content.

Long-lasting cellular immunity to SARS-CoV-2 following infection or vaccination and implications for booster strategies

Immunization against SARS-CoV-2, the causative agent of coronavirus disease-19 (COVID-19) occurs via natural infection or vaccination. However, it is currently unknown how long infection- or vaccination-induced immunological memory will last. We performed a longitudinal evaluation of immunological memory to SARS-CoV-2 following mRNA vaccination in naïve and COVID-19 recovered individuals. We found that cellular immunity is still detectable 8 months after vaccination, while antibody levels decline significantly especially in naïve subjects. We also found that a booster injection is more efficacious in reactivating immunological memory to spike protein in naïve than in previously SARS-CoV-2 infected subjects. Finally, we observed a similar kinetics of decay of humoral and cellular immunity to SARS-CoV-2 up to one year following natural infection in a cohort of unvaccinated individuals. Short-term persistence of humoral immunity may account for reinfections and breakthrough infections, although long-lived memory B and CD4+ T cells may protect from severe disease. A booster dose restores optimal anti-spike immunity in naïve subjects, while the need for vaccinated COVID-19 recovered subjects has yet to be defined.

Peptide Aggregation Induced Immunogenic Rupture (PAIIR)

Under the influence of stress and membrane damage, cells undergo immunogenic cell death (ICD), which involves the release of damage associated molecular patterns (DAMPs), natural adjuvants for enhancing an immune response. In the presence of an antigen, released DAMPs can determine the type and magnitude of the immune response, and therefore the longevity and efficacy of an antigen-specific immunity. In the last decade, the immune response effect of ICD has been shown, yet there is no tool that can induce controlled ICD with predictable results, regardless of the cell type. We designed a peptide-based tool, called [II], for controlled damage to cell membrane to induce ICD and DAMPs release. Herein we describe a series of experiments that determine that the mechanism of action of [II] includes a caspase-dependent ICD and subsequent release of immune stimulating DAMPs, on various cell types. Moreover, we tested the hypothesis that controlled DAMP release via [II] in vivo was associated with enhancement of antigen-specific adaptive immunity with influenza hemagglutinin (HA) subunit vaccine. HA and [II] showed significantly higher HA specific IgG1 and IgG2a antibodies, compared to HA-only immunized mice, while the peptide itself did not elicit antibodies. In this paper, we demonstrate the first peptide-aggregation induced immunogenic rupture (PAIIR) approach as vaccine adjuvants for increasing both humoral and cellular immunity. In consideration of its ability to enhance IgG2a responses that are associated with heterosubtypic influenza virus protection, PAIIR is a promising adjuvant to promote universal protection upon influenza HA vaccination.

Immunogenicity after Second ChAdOx1 nCoV-19 (AZD1222) Vaccination According to the Individual Reactogenicity, Health Status and Lifestyle

The immune-acquired responses after vaccination vary depending on the type of vaccine and the individual. The purpose of this study was to investigate the relationship between the acquisition of immunity and the side effects, health status, and lifestyle after completion of the second dose of AZD1222. Blood samples were collected after a second dose of AZD1222. The Euroimmun Anti-SARS-CoV-2 ELISA (IgG) for anti-S1 antibody, the cPASS SARS-CoV-2 neutralizing antibody detection kit for the surrogate virus neutralization test, and the T-spot Discovery SARS-CoV-2 kit were used to identify cellular immunogenicity. Patient experience of adverse effects was investigated using questionnaires. Information on health status and lifestyle were collected from the most recent health checkup data. Generally, females experience more reactogenicity in both intensity and duration. The rash of the first shot and chills of the second shot were associated with humoral immunity. However, comprehensive adverse effects had no correlation with humoral and cellular immunity. The T-spot-positive group had a higher creatinine level, which reflects muscle mass, than the T-spot-negative group. Males presented a higher level of T-spot assays. Body mass index and age were negatively correlated with the T-spot assay and anti-S1 antibody, respectively. Immune acquisition after the second AZD1222 shot was not associated with reactogenicity. However, individuals’ sex, age, and BMI were found to be associated with immunogenicity after vaccination.

Foxp3+ CD4+ regulatory T cells control dendritic cells in inducing antigen-specific immunity to emerging SARS-CoV-2 antigens

Regulatory T (Treg) cells, which constitute about 5–10% of CD4+T cells expressing Foxp3 transcription factor and CD25(IL-2 receptor α chain), are key regulators in controlling immunological self-tolerance and various immune responses. However, how Treg cells control antigen-specific immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains unclear. In this study, we examined the effect of transient breakdown of the immunological tolerance induced by Treg-cell depletion on adaptive immune responses against administered SARS-CoV-2 antigen, spike protein 1 (S1). Notably, without the use of adjuvants, transient Treg-cell depletion in mice induced anti-S1 antibodies that neutralized authentic SARS-CoV-2, follicular helper T cell formation and S1-binding germinal center B cell responses, but prevented the onset of developing autoimmune diseases. To further clarify the mechanisms, we investigated maturation of dendritic cells (DCs), which is essential to initiate antigen-specific immunity. We found that the transient Treg-cell depletion resulted in maturation of both migratory and resident DCs in draining lymph nodes that captured S1-antigen. Moreover, we observed S1-specific CD4+ T cells and CD8+ T cells with interferon-γ production. Thus, captured S1 was successfully presented by DCs, including cross-presentation to CD8+ T cells. These data indicate that transient Treg-cell depletion in the absence of adjuvants induces maturation of antigen-presenting DCs and succeeds in generating antigen-specific humoral and cellular immunity against emerging SARS-CoV-2 antigens. Finally, we showed that SARS-CoV-2 antigen-specific immune responses induced by transient Treg-cell depletion in the absence of adjuvants were compatible with those induced with an effective adjuvant, polyriboinosinic:polyribocytidyl acid (poly IC) and that the combination of transient Treg-cell depletion with poly IC induced potent responses. These findings highlight the capacity for manipulating Treg cells to induce protective adaptive immunity to SARS-CoV-2 with activating antigen-presenting DCs, which may improve the efficacy of ongoing vaccine therapies and help enhance responses to emerging SARS-CoV-2 variants.

Humoral and cellular responses to SARS-CoV-2 vaccination in patients with lymphoid malignancies

SUMMARYSARS-CoV-2 vaccination protects against COVID-19. Antibodies and antigen-specific T-cell responses against the spike domain can be used to measure vaccine immune response. Individuals with lymphoma have defects in humoral and cellular immunity that may compromise vaccine response. In this prospective observational study of 457 participants with lymphoma, 52% of participants vaccinated on treatment had undetectable anti-spike IgG antibodies compared to 9% who were not on treatment. Marked impairment was observed in those receiving anti- CD20 antibody within 12 months where 60% had undetectable antibodies compared to 11% on chemotherapy, which persisted despite three vaccine doses. Overall, 63% had positive T-cell responses irrespective of treatment. Individuals with indolent B-cell lymphoma have impaired antibody and cellular responses that were independent of treatment. The significant reduction and heterogeneity in immune responses in these individuals emphasise the urgent need for immune response monitoring and alternative prophylactic strategies to protect against COVID- 19.