Initial Mix-and-Match COVID-19 Vaccination Perceptions, Concerns, and Side Effects across Canadians

Research indicates that mixing the first two doses of COVID-19 vaccine types (i.e., adenoviral vector and mRNA) produces potent immune responses against the coronavirus, but it is unclear how individuals may perceive these benefits, or whether there are different concerns compared to individuals who received two doses of the same vaccine. This research examines the demographic characteristics, psychological perceptions, and vaccination-related opinions and experiences of a large Canadian sample (N = 1002) who had received two initial doses of any COVID-19 vaccine combination. Participants included 791 (78.9%) who received two doses of the exact same brand and type of vaccine, 164 (16.4%) who received two doses of the same type of vaccine (i.e., either mRNA or adenoviral vector) but from different brands (e.g., Pfizer-BioNTech + Moderna), and 47 (4.7%) who received two doses from different types and brands of vaccine (e.g., Oxford-AstraZeneca + Pfizer-BioNTech). Results showed that, after the first vaccine dose, participants who received an adenoviral vector vaccine (e.g., Oxford-AstraZeneca) experienced the highest number of common side effects, and more severe levels of each side effect compared to those who received an mRNA vaccine (e.g., Pfizer-BioNTech or Moderna). After the second dose, participants who received Moderna as their second vaccine experienced the highest number of and most severe side effects, regardless of whether they received Moderna, Pfizer-BioNTech, or Oxford-AstraZeneca as their first dose. Real-world implications of these findings are discussed.

Safety and Immunogenicity of the Third Booster Dose with Inactivated, Viral Vector, and mRNA COVID-19 Vaccines in Fully Immunized Healthy Adults with Inactivated Vaccine

The coronavirus disease 2019 (COVID-19) pandemic has become a severe healthcare problem worldwide since the first outbreak in late December 2019. Currently, the COVID-19 vaccine has been used in many countries, but it is still unable to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, despite patients receiving full vaccination doses. Therefore, we aimed to appraise the booster effect of the different platforms of vaccines, including inactivated vaccine (BBIBP), viral vector vaccine (AZD122), and mRNA vaccine (BNT162b2), in healthy adults who received the full dose of inactivated vaccine (CoronaVac). The booster dose was safe with no serious adverse events. Moreover, the immunogenicity indicated that the booster dose with viral vector and mRNA vaccine achieved a significant proportion of Ig anti-receptor binding domain (RBD), IgG anti-RBD, and IgA anti-S1 booster response. In contrast, inactivated vaccine achieved a lower booster response than others. Consequently, the neutralization activity of vaccinated serum had a high inhibition of over 90% against SARS-CoV-2 wild-type and their variants (B.1.1.7–alpha, B.1.351–beta, and B.1.617.2–delta). In addition, IgG anti-nucleocapsid was observed only among the group that received the BBIBP booster. Our study found a significant increase in levels of IFN-ɣ secreting T-cell response after the additional viral vector or mRNA booster vaccination. This study showed that administration with either viral vector (AZD1222) or mRNA (BNT162b2) boosters in individuals with a history of two doses of inactivated vaccine (CoronaVac) obtained great immunogenicity with acceptable adverse events.

Timing of Breakthrough Infection Risk After Vaccination Against SARS-CoV-2

Background: Provision of safe and effective vaccines has been a remarkable public health achievement during the SARS-CoV-2 pandemic. The effectiveness and durability of protection of the first two doses of SARS-CoV-2 vaccines is an important area for study, as are questions related to optimal dose combinations and dosing intervals. Methods: We performed a case-cohort study to generate real-world evidence on efficacy of first and second dose of SARS-CoV-2 vaccines, using a population-based case line list and vaccination database for the province of Ontario, Canada between December 2020 and October 2021. Risk of infection after vaccination was evaluated in all laboratory-confirmed vaccinated SARS-CoV-2 cases, and a 2% sample of vaccinated controls, evaluated using survival analytic methods, including construction of Cox proportional hazards models. Vaccination status was treated as a time-varying covariate. Results: First and second doses of SARS-CoV-2 vaccine markedly reduced risk of infection (first dose efficacy 68%, 95% CI 67% to 69%; second dose efficacy 88%, 95% CI 87 to 88%). In multivariable models, extended dosing intervals were associated with lowest risk of breakthrough infection (HR for redosing 0.64 (95% CI 0.61 to 0.67) at 6-8 weeks). Heterologous vaccine schedules that mixed viral vector vaccine first doses with mRNA second doses were significantly more effective than mRNA only vaccines. Risk of infection largely vanished during the time period 4-6 months after the second vaccine dose, but rose markedly thereafter. Interpretation: A case-cohort design provided an efficient means to identify strong protective effects associated with SARS-CoV-2 vaccination, particularly after the second dose of vaccine. However, this effect appeared to wane once more than 6 months had elapsed since vaccination. Heterologous vaccination and extended dosing intervals improved the durability of immune response.

Immunogenicity and safety of adenovirus-based vector vaccines for COVID-19: a systematic review and meta-analysis

BACKGROUND Despite various research on vaccine development, severe acute respiratory syndrome coronavirus 2 infection continues to spread. Thus, developing a more effective vaccine for production and clinical efficacy is still in high demand. This review aimed to assess the immunogenicity and safety of adenovirus-based vector vaccine (Ad-vaccines) including Ad5-vectored, ChAdOx1 nCoV-19, rAd26-S or rAd5-S, and Ad26.COV2.S as the promising solutions for COVID-19. METHODS We conducted a systematic review and meta analysis of clinical trials based on the preferred reporting items for systematic reviews and meta-analyses guidelines through PubMed, Scopus, Cochrane, and EBSCOhost until August 17, 2021. We implemented inclusion and exclusion criteria and assessed the studies using OHAT risk of bias rating tool for human and animal studies. Pooled estimates of odds ratio (OR) were analyzed using fixed-effect model. RESULTS This systematic review yielded 12 clinical studies with a total of 75,105 subjects. Although the studies were heterogeneous, this meta-analysis showed that Ad-vaccine significantly increased protection and immune response against COVID-19 with a pooled efficacy of 84.68% compared to placebo (p<0.00001). Forest plot also indicated that Ad-vaccine conferred protection against moderate to severe COVID-19 with a pooled OR of 0.26 (p<0.00001). Ad-vaccine had also shown a good safety profile with local site pain and fever as the most common side effects. CONCLUSIONS Ad-vaccine had shown a good immunogenicity for COVID-19 with a good pooled efficacy and was proven safe for COVID-19 patients.

Evaluation of Antibody Response to Heterologous Prime–Boost Vaccination with ChAdOx1 nCoV-19 and BNT162b2: An Observational Study

In several countries, thrombotic events after vaccination with ChAdOx1 nCoV-19 have led to heterologous messenger RNA (mRNA) boosting. We tested the antibody response to SARS-CoV-2 spike protein four weeks after heterologous priming with the ChAdOx1 (ChAd) vector vaccine followed by boosting with BNT162b2(ChAd/BNT), comparing data of homologous regimen (BNT/BNT, ChAd/ChAd) subjects positive for SARS-CoV-2 after the first dose of BNT162b2 (BNT1dose/CoV2) and convalescent COVID-19. Methods: healthy subjects naïve for SARS-CoV-2 infection were assessed for serum IgG anti-S-RBD response 21 days after priming (T1), 4 (TFULL) and 15 (T15W) weeks after booster dose. Results: The median IgG anti-S-RBD levels at TFULL of Chad/BNT group were significantly higher than the BNT/BNT group and ChAd/ChAd. Those of BNT/BNT group were significantly higher than ChAd/ChAd. IgG anti-S-RBD of BNT1dose/CoV2 group were similar to BNT/BNT, ChAd/BNT and ChAd/Chad group. The levels among COVID-19 convalescents were significantly lower than ChAd/BNT, BNT/BNT, ChAd/Chad and BNT1dose/CoV2. The proportion of subjects reaching an anti-S-RBD titer >75 AU/mL, correlated with high neutralizing titer, was 94% in ChAd/BNT and BNT/BNT, 60% in BNT1dose/CoV2, 25% in ChAd/ChAd and 4.2% in convalescents. At T15W the titer of ChAd/BNT was still significantly higher than other vaccine schedules, while the anti-S-RBD decline was reduced for ChAd/ChAd and similar for other combinations. Conclusion: Our data highlight the magnitude of IgG anti-S-RBD response in ChAd/BNT dosing, supporting the current national guidelines for heterologous boosting

Safety and immunogenicity of a heterologous booster of protein subunit vaccine MVC-COV1901 after two doses of adenoviral vector vaccine AZD1222

We report the interim safety and immunogenicity results in participants administrated with a booster dose of protein subunit vaccine MVC-COV1901 at 12 or 24 weeks after two doses of AZD1222 (ChAdOx1 nCoV-19). In subjects fully vaccinated with two doses of AZD1222, waning antibody immunity was apparent within six months of the second dose of AZD1222. At one month after the MVC-COV1901 booster dose, anti-SARS-CoV-2 spike IgG antibody titers and neutralizing antibody titers were 14- and 8.6-fold increased, respectively, when compared to the titer levels on the day of the booster dose. These interim results support the use of MVC-COV1901 as a heterologous booster for individuals vaccinated with AZD1222.

A single intranasal dose of a live-attenuated parainfluenza virus-vectored SARS-CoV-2 vaccine is protective in hamsters

Single-dose vaccines with the ability to restrict SARS-CoV-2 replication in the respiratory tract are needed for all age groups, aiding efforts toward control of COVID-19. We developed a live intranasal vector vaccine for infants and children against COVID-19 based on replication-competent chimeric bovine/human parainfluenza virus type 3 (B/HPIV3) that express the native (S) or prefusion-stabilized (S-2P) SARS-CoV-2 S spike protein, the major protective and neutralization antigen of SARS-CoV-2. B/HPIV3/S and B/HPIV3/S-2P replicated as efficiently as B/HPIV3 in vitro and stably expressed SARS-CoV-2 S. Prefusion stabilization increased S expression by B/HPIV3 in vitro. In hamsters, a single intranasal dose of B/HPIV3/S-2P induced significantly higher titers compared to B/HPIV3/S of serum SARS-CoV-2–neutralizing antibodies (12-fold higher), serum IgA and IgG to SARS-CoV-2 S protein (5-fold and 13-fold), and IgG to the receptor binding domain (10-fold). Antibodies exhibited broad neutralizing activity against SARS-CoV-2 of lineages A, B.1.1.7, and B.1.351. Four weeks after immunization, hamsters were challenged intranasally with 104.5 50% tissue-culture infectious-dose (TCID50) of SARS-CoV-2. In B/HPIV3 empty vector-immunized hamsters, SARS-CoV-2 replicated to mean titers of 106.6 TCID50/g in lungs and 107 TCID50/g in nasal tissues and induced moderate weight loss. In B/HPIV3/S-immunized hamsters, SARS-CoV-2 challenge virus was reduced 20-fold in nasal tissues and undetectable in lungs. In B/HPIV3/S-2P–immunized hamsters, infectious challenge virus was undetectable in nasal tissues and lungs; B/HPIV3/S and B/HPIV3/S-2P completely protected against weight loss after SARS-CoV-2 challenge. B/HPIV3/S-2P is a promising vaccine candidate to protect infants and young children against HPIV3 and SARS-CoV-2.

Safety and immunogenicity of the third booster dose with inactivated, viral vector, and mRNA COVID-19 vaccines in fully immunized healthy adults with inactivated vaccine

The coronavirus disease-2019 (COVID-19) pandemic has become a severe healthcare problem worldwide since the first outbreak in late December 2019. Currently, the COVID-19 vaccine has been used in many countries, but it is still unable to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection despite patients receiving full vaccination doses. Therefore, we aimed to appraise the booster effect of the different platforms of vaccines, including inactivated vaccine (BBIBP), viral vector vaccine (AZD122), and mRNA vaccine (BNT162b2) in healthy adults who received the full dose of inactivated vaccine (CoronaVac). The booster dose was safe with no serious adverse events. Moreover, the immunogenicity indicated that the booster dose with viral vector and mRNA vaccine achieved a significant proportion of Ig anti-receptor binding domain (RBD), IgG anti-RBD, and IgA anti-S1 booster response. In contrast, inactivated vaccine achieved a lower booster response than others. Consequently, the neutralization activity of vaccinated serum had a high inhibition of over 90% against SARS-CoV-2 wild-type and their variants (B.1.1.7–alpha, B.1.351–beta, and B.1.617.2–delta). In addition, IgG anti-nucleocapsid was observed only among the group that received the BBIBP booster. Our study found a significant increase in levels of interferon gamma-secreting T-cell response after the additional viral vector or mRNA booster vaccination. This study showed that administration with either viral vector (AZD1222) or mRNA (BNT162b2) boosters in individuals with a history of two doses of inactivated vaccine (CoronaVac) obtained great immunogenicity with acceptable adverse events.

Immunogenicity, safety and reactogenicity of a heterogeneous booster following the CoronaVac inactivated SARS-CoV-2 vaccine in patients with SLE: a case series

Since the COVID-19 pandemic, CoronaVac, an inactivated SARS-CoV-2 vaccine, has been widely deployed in several countries for emergency use. However, the immunogenicity of the inactivated vaccine was relatively lower when compared to other vaccine types and was even more attenuated in autoimmune patients with rheumatic disease. A third-dose SARS-CoV-2 vaccination in immunosuppressed population is recommended in order to improve immune response. However, the data were limited to those initially received mRNA or viral vector SARS-CoV-2 vaccine. Thus, we aimed to describe the safety, reactogenicity and immunogenicity of patients with systemic lupus erythematosus (SLE) who received a heterogenous booster SARS-CoV-2 vaccine following the initial CoronaVac inactivated vaccine series. Our findings support that the third booster dose of mRNA or viral vector vaccine following the inactivated vaccine is well tolerated and elicited a substantial humoral and cellular immune response in inactive patients with SLE having maintenance immunosuppressive therapy without interruption of immunosuppressive medications.