RESUMEN
In this South African phase 1/2b study, we demonstrated vaccine efficacy (VE) of two doses of AZD1222 for asymptomatic and symptomatic SARS-CoV-2 infection: 90.6% against wild-type and 77.1% against the Delta variant [≥]9 months after vaccination. VE against infection with the Beta variant, which preceded circulation of Delta, was 6.7%. Clinical trial identifierCT.gov NCT04444674
RESUMEN
We investigated Omicron infections among healthcare workers (HCW) presenting with symptoms of SARS-CoV-2 infection and evaluated the protective effect of vaccination or prior infection. Between 24th November and 31st December 2021, HCW in Johannesburg, South Africa, were tested for SARS-CoV-2 infection by Nucleic Acid Amplification Test (NAAT). Blood samples collected either at the symptomatic visit or within 3-months prior, were tested for spike protein immunoglobulin G (IgG). Overall, 433 symptomatic HCW were included in the analysis, with 190 (43.9%) having an Omicron infection; 69 (16.7%) were unvaccinated and 270 (62.4%) received a single dose of Ad26.COV.2 vaccine. There was no difference in the odds of identifying Omicron between unvaccinated and Ad26.COV.2 vaccinated HCW (adjusted odds ratio [aOR] 0.81, 95% confidence interval [CI]: 0.46, 1.43). One-hundred and fifty-four (35.3%) HCW had at least one SARS-CoV-2 NAAT-confirmed prior infection; these had lower odds of Omicron infection compared with those without past infection (aOR 0.55, 95%CI: 0.36, 0.84). Anti-spike IgG concentration of 1549 binding antibody unit/mL was suggestive of significant reduction in the risk of symptomatic Omicron infection. We found high reinfection and vaccine breakthrough infection rates with the Omicron variant among HCW. Prior infection and high anti-spike IgG concentration were protective against Omicron infection.
RESUMEN
On the 24th November 2021 the sequence of a new SARS CoV-2 viral isolate spreading rapidly in Southern Africa was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titres of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic as well as Alpha, Beta, Gamma, Delta are substantially reduced or fail to neutralize. Titres against Omicron are boosted by third vaccine doses and are high in cases both vaccinated and infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of a large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses, combining mutations conferring tight binding to ACE2 to unleash evolution driven by immune escape, leading to a large number of mutations in the ACE2 binding site which rebalance receptor affinity to that of early pandemic viruses.
RESUMEN
Global genomic surveillance of SARS-CoV-2 has identified variants associated with increased transmissibility, neutralization resistance and disease severity. Here we report the emergence of the PANGO lineage C.1.2, detected at low prevalence in South Africa and eleven other countries. The emergence of C.1.2, associated with a high substitution rate, includes changes within the spike protein that have been associated with increased transmissibility or reduced neutralization sensitivity in SARS-CoV-2 VOC/VOIs. Like Beta and Delta, C.1.2 shows significantly reduced neutralization sensitivity to plasma from vaccinees and individuals infected with the ancestral D614G virus. In contrast, convalescent donors infected with either Beta or Delta showed high plasma neutralization against C.1.2. These functional data suggest that vaccine efficacy against C.1.2 will be equivalent to Beta and Delta, and that prior infection with either Beta or Delta will likely offer protection against C.1.2.
RESUMEN
BackgroundThe emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants threatens progress toward control of the Covid-19 pandemic. Evaluation of Covid-19 vaccine efficacy against SARS-CoV-2 variants is urgently needed to inform vaccine development and use. MethodsIn this phase 2a/b, multicenter, randomized, observer-blinded, placebo-controlled trial in South Africa, healthy human immunodeficiency virus (HIV)-negative adults (18 to 84 years) or medically stable people living with HIV (PLWH) (18 to 84 years) were randomized in a 1:1 ratio to receive two doses, administered 21 days apart, of either NVX-CoV2373 nanoparticle vaccine (5 {micro}g recombinant spike protein with 50 {micro}g Matrix-M1 adjuvant) or placebo. The primary endpoints were safety and vaccine efficacy [≥]7 days following the second dose against laboratory-confirmed symptomatic Covid-19 in previously SARS-CoV-2 uninfected participants. ResultsA total of 4387 participants were randomized and dosed at least once, 2199 with NVX-CoV2373 and 2188 with placebo. Approximately 30% of participants were seropositive at baseline. Among 2684 baseline seronegative participants (94% HIV-negative; 6% PLWH), there were 15 and 29 predominantly mild to moderate Covid-19 cases in NVX-CoV2373 and placebo recipients, respectively; vaccine efficacy was 49.4% (95% confidence interval [CI]: 6.1 to 72.8). Efficacy in HIV-negative participants was 60.1% (95% CI: 19.9 to 80.1), and did not differ by baseline serostatus. Of the primary endpoint cases with available whole genome sequencing, 38 (92.7%) of 41 were the B.1.351 variant. Post-hoc vaccine efficacy against B.1.351 was 51.0% (95% CI: - 0.6 to 76.2) in HIV-negative participants. Among placebo recipients, the incidence of symptomatic Covid-19 was similar in baseline seronegative vs baseline seropositive participants during the first 2 months of follow-up (5.3% vs 5.2%). Preliminary local and systemic reactogenicity were primarily mild to moderate and transient, and higher with NVX-CoV2373; serious adverse events were rare in both groups. ConclusionsThe NVX-CoV2373 vaccine was efficacious in preventing Covid-19, which was predominantly mild to moderate and due to the B.1.351 variant, while evidence of prior infection with the presumptive original SARS-CoV-2 did not confer protection against probable B.1.351 disease. (Funded by Novavax, The Bill and Melinda Gates Foundation, and the Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number, NCT04533399)
