Humoral responses to wild type and ancient BA.1 SARS-CoV-2 variant after heterologous priming vaccination with ChAdOx1 nCoV-19 and BNT162b2 booster dose.

Several countries have recommended a booster dose of Pfizer BNT162b2 vaccine for subjects under the age of 60, who have already received the first dose of ChAdOx1. This is due to several ChAdOx1 vaccine-associated adverse vascular events and thrombocytopenia. Neutralization assay and quantitative IgG anti-SARS-CoV-2 Spike antibody (anti-S-IgG) were conducted to investigate the long-term responses to vaccine treatment in a cohort of Sardinian participants, who have received heterologous Prime-Boost Vaccination via ChAdOx1 vector vaccine and a booster dose via BNT162b2. The obtained results were compared with those of a cohort of healthcare workers (HCW) who received homologous BNT162b2 (BNT/BNT/BNT) vaccination. One month (T2) and five months after the second and before the third dose (T3), anti-spike antibody or neutralizing titers in the subjects vaccinated with ChAdOx1-S/BNT162b2 were significantly higher than those who experienced the ChAdOx1-S/ChAdOx1-S or BNT162b2/BNT162b2 schedule. These results suggest that a ChAdOx1-S/BNT162b2 regimen provides a more robust antibody response than either of the homologous regimens. However, the anti-spike antibodies or neutralizing titers after the third injection (mRNA vaccine) of ChAdOx1-S as a second dose and BNT162b2 were not statistically different. Homologous and heterologous vaccination provided a strong antibody response. Neutralizing activities were also described against the Omicron BA.1 variant in a sub-group (40) representative of the three vaccination regimens among our cohort.

Safety of heterologous ChAdOx1-S/BNT162b2 primary schedule versus homologous BNT162b2 vaccination: Insights from an Italian post-marketing study, 2021.

During COVID-19 vaccination campaign, possible ChAdOx1-S-associated risks of thrombosis with thrombocytopenia syndrome led to implement ChAdOx1-S/BNT162b2 heterologous vaccination, despite the limited information on its reactogenicity and safety. We conducted a prospective observational post-marketing surveillance study to assess the safety of this heterologous schedule. A casually selected sample of recipients (n: 85; age: 18-60 years) of ChAdOx1-S/BNT162b2 at the vaccination hub of the Foggia Hospital, Italy, was matched with an equal sample of recipients of homologous BNT162b2. Safety was evaluated 7 days, 1 month and 14 weeks after the primary vaccination series using an adapted version of the "V-safe active surveillance for COVID-19 vaccine safety" CDC standardized questionnaire. After 7 days, local reactions were highly frequent (>80%) in both groups, and systemic reactions were less common (<70%). Moderate or severe pain at the injection site (OR = 3.62; 95%CI, 1.45-9.33), moderate/severe fatigue (OR = 3.40; 95%CI, 1.22-9.49), moderate/severe headache (OR = 4.72; 95%CI, 1.37-16.23), intake of antipyretics (OR = 3.05; 95 CI%, 1.35-6.88), inability to perform daily activities and work (OR = 2.64; 95%CI, 1.24-5.62) were significantly more common with heterologous than homologous vaccination. No significant difference in self-reported health status was recorded 1 month or 14 weeks after the second dose with BNT162b2 or ChAdOx1-S/BNT162b2. Our study confirms the safety of both heterologous and homologous vaccination, with a slight increase in some short-term adverse events for the heterologous regimen. Therefore, administering a second dose of a mRNA vaccine to the recipients of a previous dose of viral vector vaccine may have represented an advantageous strategy to improve flexibility and to accelerate the vaccination campaign.

Humoral and T Cell Immune Responses against SARS-CoV-2 after Primary and Homologous or Heterologous Booster Vaccinations and Breakthrough Infection: A Longitudinal Cohort Study in Malaysia.

Vaccine efficacy against SARS-CoV-2 could be compromised by the emergence of SARS-CoV-2 variants and it is important to study how it impacts the booster vaccination regime. We investigated the humoral and T cell responses longitudinally in vaccinated uninfected (n = 25) and post-COVID-19 individuals (n = 8), and those who had received a BNT162b2 booster following complete two-doses regimes of either BNT162b2 (homologous) (n = 14) or ChAdOx1-S (heterologous) (n = 15) vaccines, by means of a SARS-CoV-2 pseudovirus neutralization test and QuantiFERON SARS-CoV-2 assay. Vaccinated post-COVID-19 individuals showed higher neutralizing antibodies with longer durability against SARS-CoV-2 wild type (WT) and Omicron spikes, but demonstrated similar declining T cell responses compared to the uninfected vaccinated. Two doses of BNT162b2 induced higher neutralizing antibodies against WT and T cell responses than ChAdOx1-S for six months. The BNT162b2 booster confers a greater humoral response against WT, but a similar cross-neutralizing antibody against Omicron and T cell responses in the homologous booster group compared to the heterologous booster group. Breakthrough infection in the homologous booster group (n = 11) significantly increased the neutralizing antibody, but T cell responses remained low. Our data may impact government public health policy regarding the administration of mix-and-match vaccines, where both vaccination regimes can be employed should there be shortages of certain vaccines.

Potential Anionic Substances Binding to Platelet Factor 4 in Vaccine-Induced Thrombotic Thrombocytopenia of ChAdOx1-S Vaccine for SARS-CoV-2.

Recent reports of rare ChAdOx1-S vaccine-related venous thrombosis led to the suspension of its usage in several countries. Vaccine-induced thrombotic thrombocytopenia (VITT) is characterized by thrombocytopenia and thrombosis in association with anti-platelet factor 4 (PF4) antibodies. Herein, we propose five potential anionic substances of the ChAdOx1-S vaccine that can combine with PF4 and trigger VITT, including (1) the proteins on the surface of adenovirus, e.g., negative charged glycoprotein, (2) the adjuvant components of the vaccine, e.g., Tween 80, (3) the DNA of adenovirus, (4) the S protein antigen expressed by the vaccine, and (5) the negatively charged impurity proteins expressed by the vaccine, e.g., adenovirus skeleton proteins. After analysis of each case, we consider the most possible trigger to be the negatively charged impurity proteins expressed by the vaccine. Then, we display the possible extravascular route and intravascular route of the formation of PF4 autoantibodies triggered by the negatively charged impurity proteins, which is accordant with the clinical situation. Accordingly, the susceptible individuals of VITT after ChAdOx1-S vaccination may be people who express negatively charged impurity proteins and reach a certain high titer.