The SARS-CoV-2 Omicron (B.1.1.529) Variant of Concern (VOC) and its sub-lineages (including BA.2, BA.4/5, BA.2.12.1) contain spike mutations that confer high level resistance to neutralizing antibodies. The NVX-CoV2373 vaccine, a protein nanoparticle vaccine, has value in countries with constrained cold-chain requirements. Here we report neutralizing titers following two or three doses of NVX-CoV2373. We show that after two doses, Omicron sub-lineages BA.1 and BA.4 were resistant to neutralization by 72% (21/29) and 59% (17/29) of samples. However, after a third dose of NVX-CoV2373, we observed high titers against Omicron BA.1 (GMT: 1,197) and BA.4 (GMT: 582), with responses similar in magnitude to those triggered by three doses of an mRNA vaccine. These data are of particular relevance as BA.4 is emerging to become the dominant strain in many locations, and highlight the potential utility of the NVX-CoV2373 vaccine as a booster in resource-limited environments.
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
BackgroundThe B.1.1.529 (Omicron BA.1) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global resurgence of coronavirus disease 2019 (Covid-19). The contribution of BA.1 infection to population immunity and its effect on subsequent resurgence of B.1.1.529 sub-lineages warrant investigation. MethodsWe conducted an epidemiologic survey to determine the sero-prevalence of SARS-CoV-2 IgG from March 1 to April 11, 2022, after the BA.1-dominant wave had subsided in Gauteng (South Africa), and prior to a resurgence of Covid-19 dominated by the BA.4 and BA.5 (BA.4/BA.5) sub-lineages. Population-based sampling included households in an earlier survey from October 22 to December 9, 2021 preceding the BA.1 dominant wave. Dried-blood-spot samples were quantitatively tested for IgG against SARS-CoV-2 spike protein and nucleocapsid protein. Epidemiologic trends in Gauteng for cases, hospitalizations, recorded deaths, and excess deaths were evaluated from the inception of the pandemic to the onset of the BA.1 dominant wave (pre-BA.1), during the BA.1 dominant wave, and for the BA.4/BA.5 dominant wave through June 6, 2022. ResultsThe 7510 participants included 2420 with paired samples from the earlier survey. Despite only 26.7% (1995/7470) of individuals having received a Covid-19 vaccine, the overall sero-prevalence was 90.9% (95% confidence interval [CI], 90.2 to 91.5), including 89.5% in Covid-19 unvaccinated individuals. Sixty-four percent (95%CI, 61.8-65.9) of individuals with paired samples had serological evidence of SARS-CoV-2 infection during the BA.1 dominant wave. Of all cumulative recorded hospitalisations and deaths, 14.1% and 5.9% were contributed by the BA.1 dominant wave, and 5.1% and 1.6% by the BA.4/BA.5 dominant wave. The SARS-CoV-2 infection fatality risk was lower in the BA.1 compared with pre-BA.1 waves for recorded deaths (0.02% vs. 0.33%) and Covid-19 attributable deaths based on excess mortality estimates (0.03% vs. 0.67%). ConclusionsGauteng province experienced high levels of infections in the BA.1 -dominant wave against a backdrop of high (73%) sero-prevalence. Covid-19 hospitalizations and deaths were further decoupled from infections during BA.4/BA.5 dominant wave than that observed during the BA.1 dominant wave. (Funded by the Bill and Melinda Gates Foundation.)
BackgroundThe rapid development of vaccines in response to the COVID-19 pandemic has provided an effective tool for the management of COVID-19. However, in Africa there has been a poor uptake of COVID-19 vaccines with only 15% vaccine coverage compared to the WHO global target of 70%. One of the important drivers has been vaccine hesitancy, understanding late adopters of vaccination can provide insights into the attitudes, motivations and influences that can enhance vaccine uptake. MethodsBetween January 4 - February 11, 2022, we conducted a survey among adults presenting for their first dose of a COVID-19 vaccine almost 12-months after the vaccination program began. Vaccines were free and provided at clinics and outreach centers in Harare, Zimbabwe. The questionnaire assessed environmental and individual factors (attitudes, barriers, motivations, key influencers, and information sources) that influenced the decision to present for vaccination. Baseline socio-demographic data and responses to survey questions were summarized using descriptive statistics. Binary logistic regression models were developed to understand factors associated with vaccine confidence. Results1016 adults were enrolled into the study, 508 (50%) were female, 126 (12.4%) had HIV co-infection. The median age was 30 years (IQR 22 - 39). Women were more likely to have negative views about the COVID-19 vaccine compared to men (OR 1.51 (95%CI 1.16, 1.97, p=0.002). Women compared to men and older adults ([≥] 40 years) compared with youth (18-25 years) were more likely to have major concerns about vaccines. Most concerns were about safety with 602 (59.3%) concerned about immediate and 520 (51.2%) about long-term health effects of vaccines. People living with HIV (PLWH) were more likely to perceive vaccines as safe (OR 1.71 (95%CI: 1.07, 2.74, p=0.025), effective (1.68 (95%CI: 1.07, 2.64, p=0.026) and to trust regulatory systems for approving vaccines (OR 1.79 (95% CI: 1.11, 2.89, p=0.017) compared to those without HIV. Internet users were less likely to perceive vaccines as safe (OR 0.72 (95% CI: 0.55, 0.95, p=0.021), effective (OR 0.61 (95% CI: 0.47, 0.80, p<0.001) or trust regulatory processes for approving vaccines (OR 0.64 (95% CI: 0.48, 0.85, p=0.002) compared to non-internet users. Social influence was a key factor in the decision to be vaccinated with family members being the primary key influencers for 560 (55.2%) participants. The most important reason for receiving the COVID-19 vaccine today for 715 (70.4%) participants was the protection of individual health. The most trusted source of information regarding the vaccine was the Ministry of Health (79.7%) and the radio, television and social media were the preferred sources for obtaining this information. Social media was a more likely source for youth and those with higher levels of education. ConclusionImproving vaccine coverage will need targeted communication strategies that address negative perceptions of vaccines and associated safety and effectiveness concerns. Leveraging normative behavior as a social motivator for vaccination will be important as close social networks are key influences of vaccination. Traditional media remains important for health communication in Africa and should be strengthened to counter social media-based misinformation that drives concerns about safety and effectiveness particularly among internet users.
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.
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.
BackgroundWe conducted a seroepidemiological survey from October 22 to December 9, 2021, in Gauteng Province, South Africa, to determine SARS-CoV-2 immunoglobulin G (IgG) seroprevalence primarily before the fourth wave of coronavirus disease 2019 (Covid-19), in which the B.1.1.529 (Omicron) variant was dominant. We evaluated epidemiological trends in case rates and rates of severe disease through to January 12, 2022, in Gauteng. MethodsWe contacted households from a previous seroepidemiological survey conducted from November 2020 to January 2021, plus an additional 10% of households using the same sampling framework. Dry blood spot samples were tested for anti-spike and anti-nucleocapsid protein IgG using quantitative assays on the Luminex platform. Daily case, hospital admission, and reported death data, and weekly excess deaths, were plotted over time. ResultsSamples were obtained from 7010 individuals, of whom 1319 (18.8%) had received a Covid-19 vaccine. Overall seroprevalence ranged from 56.2% (95% confidence interval [CI], 52.6 to 59.7) in children aged <12 years to 79.7% (95% CI, 77.6 to 81.5) in individuals aged >50 years. Seropositivity was more likely in vaccinated (93.1%) vs unvaccinated (68.4%) individuals. Epidemiological data showed SARS-CoV-2 infection rates increased and subsequently declined more rapidly than in previous waves. Infection rates were decoupled from Covid-19 hospitalizations, recorded deaths, and excess deaths relative to the previous three waves. ConclusionsWidespread underlying SARS-CoV-2 seropositivity was observed in Gauteng Province before the Omicron-dominant wave. Epidemiological data showed a decoupling of hospitalization and death rates from infection rate during Omicron circulation.
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.
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)
