Immunogenicity and safety of Sinovac-CoronaVac booster vaccinations in 12-17- year-olds with clinically significant reactions from Pfizer-BNT162b2 vaccination.

Heterologous Sinovac-CoronaVac booster(s) in 12-17-year-olds who had a moderate/severe reaction to Pfizer-BNT162b2 mRNA vaccine was found to safe with no serious adverse events reported. In those primed with 1 dose of Pfizer-BNT162b2 vaccine, subsequent boosters with 2 doses of Sinovac-CoronaVac vaccines achieved neutralizing antibody levels which were comparable to those who had received 2 doses of Pfizer-BNT162b2 vaccines followed by 1 dose of Sinovac-CoronaVac vaccination. Adolescents with 1 Pfizer-BNT162b2 followed by 2 Sinovac-CoronaVac vaccines developed T-cell responses against broad peptides including membrane, nucleoprotein 1 and 2 but levels were highest for Spike protein and lasted until day 150 post-vaccination.

Use of a point-of-care test to rapidly assess levels of SARS-CoV-2 nasal neutralising antibodies in vaccines and breakthrough infected individuals.

Despite SARS-CoV-2 vaccines eliciting systemic neutralising antibodies (nAbs), breakthrough infections still regularly occur. Infection helps to generate mucosal immunity, possibly reducing disease transmission. Monitoring mucosal nAbs is predominantly restricted to lab-based assays, which have limited application to the public. In this multi-site study, we used lateral-flow surrogate neutralisation tests to measure mucosal and systemic nAbs in vaccinated and breakthrough infected individuals in Australia and Singapore. Using three lateral flow assays to detect SARS-CoV-2 nAbs, we demonstrated that nasal mucosal nAbs were present in 71.4 (95% CI 56.3-82.9%) to 85.7% (95% CI 71.8-93.7%) of individuals with breakthrough infection (positivity rate was dependent upon the type of test), whereas only 20.7 (95% CI 17.1-49.4%) to 34.5% (95% CI 19.8-52.7%) of vaccinated individuals without breakthrough infection had detectible nasal mucosal nAbs. Of the individuals with breakthrough infection, collective mucosal anti-S antibody detection in confirmatory assays was 92.9% (95% CI 80.3-98.2%) of samples, while 72.4% (95% CI 54.1-85.5%) of the vaccinated individuals who had not experienced a breakthrough infection were positive to anti-S antibody. All breakthrough infected individuals produced systemic anti-N antibodies; however, these antibodies were not detected in the nasal cavity. Mucosal immunity is likely to play a role in limiting the transmission of SARS-CoV-2 and lateral flow neutralisation tests provide a rapid readout of mucosal nAbs at the point-of-care.

BNT162b2 vaccine induced variant-specific immunity, safety and risk of Omicron breakthrough infection in children aged 5 to 11 years: a cohort study.

There is little information on BNT162b2 vaccine-induced variant-specific immunogenicity, safety data and dynamics of breakthrough infections in pediatric populations. We addressed these questions using a prospective two dose BNT162b2 (10 mcg) vaccination cohort study of healthy children 5-11 years in Singapore. Follow up included blood samples at scheduled visits, daily vaccination symptom diary and confirmation of SARS-CoV-2 infection. Surrogate virus neutralization test (sVNT) and spike-specific T cell responses against SARS-CoV-2 variants were performed. The mean age of 127 participants was 8.27 years (SD 1.95) and 51.2% were males. The median sVNT level against original variant after 1 dose and 2 dose vaccination was 61.4% and 95.1% respectively (p < 0.0001). Neutralizing antibodies against the Omicron variant was the lowest, median 22.4% (IQR 16.5-30.8). However, T cell IFN-γ cytokine response against Omicron variant was high and remained so about 4 months after vaccination. Fever rate increased significantly from 4% (dose 1) to 11.5% (dose 2). The risk of Omicron breakthrough infection decreased by 7.8% for every 1% increase in sVNT inhibition level measured after dose 2 vaccination. BNT162b2 vaccines were safe, induced good T cell responses but poor neutralizing antibodies against Omicron in children. Low neutralizing antibody levels post-vaccination was predictive of subsequent breakthrough infection.

Distinctive serotypes of SARS-related coronaviruses defined by convalescent sera from unvaccinated individuals.

Multiple Omicron sub-lineages have emerged, with Omicron XBB and XBB.1.5 subvariants becoming the dominant variants globally at the time of this study. The key feature of new variants is their ability to escape humoral immunity despite the fact that there are limited genetic changes from their preceding variants. This raises the question of whether Omicron should be regarded as a separate serotype from viruses serologically clustered with the ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Here, we present cross-neutralization data based on a pseudovirus neutralization test using convalescent sera from naïve individuals who had recovered from primary infection by SARS-CoV-1 and SARS-CoV-2 strains/variants including the ancestral virus and variants Beta, Delta, Omicron BA.1, Omicron BA.2 and Omicron BA.5. The results revealed no significant cross-neutralization in any of the three-way testing for SARS-CoV-1, ancestral SARS-CoV-2 and SARS-CoV-2 Omicron subvariants. The data argue for the assignment of three distinct serotypes for the currently known human-infecting SARS-related coronaviruses.

SARS-CoV-2 Omicron variant emerged under immune selection.

The SARS-CoV-2 Omicron variant (B.1.1.529 lineage) escapes antibodies that neutralize the ancestral virus. We tested human serum panels from participants with differing infection and vaccination status using a multiplex surrogate virus neutralization assay targeting 20 sarbecoviruses. We found that bat and pangolin sarbecoviruses showed significantly less neutralization escape than the Omicron variant. We propose that SARS-CoV-2 variants have emerged under immune selection pressure and are evolving differently from animal sarbecoviruses.

Differential escape of neutralizing antibodies by SARS-CoV-2 Omicron and pre-emergent sarbecoviruses.

The SARS-CoV-2 B.1.1.529 lineage, Omicron variant, was first detected in November 2021 and carries 32 amino acid mutations in the spike protein (15 in RBD) and exhibits significant escape of neutralizing antibodies targeting the parental SARS-CoV-2 virus. Here, we performed a high-resolution multiplex (16-plex) surrogate virus neutralization assay covering all major SARS-CoV-2 variants and pre-emergent ACE2-binding sarbecoviruses against 20 different human serum panels from infected, vaccinated and hybrid immune individuals which had vaccine-breakthrough infections or infection followed by vaccination. Among all sarbecoviruses tested, we observed 1.1 to 4.7-, 2.3 to 10.3- and 0.7 to 33.3-fold reduction in neutralization activities to SARS-CoV-2 Beta, Omicron and SARS-CoV-1, respectively. Among the SARS-CoV-2 related sarbecoviruses, it is found that the genetically more distant bat RaTG13 and pangolin GX-P5L sarbecoviruses had less neutralization escape than Omicron. Our data suggest that the SARS-CoV-2 variants emerged from the changed immune landscape of human populations are more potent in escaping neutralizing antibodies, from infection or vaccination, than pre-emergent sarbecoviruses naturally evolved in animal populations with no or less immune selection pressure.