Background The 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. Methods In 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 μg recombinant spike protein with 50 μg 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. Results A 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), 15 and 29 predominantly mild to moderate Covid-19 cases were noted 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; 38 (92.7%) of 41 sequenced cases 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. 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. Conclusions The NVX-CoV2373 vaccine was efficacious in preventing Covid-19, which was predominantly mild to moderate and due to the B.1.351 variant.

Background The 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. Methods In 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 micrograms recombinant spike protein with 50 micrograms Matrix-M1 adjuvant) or placebo. The primary endpoints were safety and vaccine efficacy greater than or equal to 7 days following the second dose against laboratory-confirmed symptomatic Covid-19 in previously SARS-CoV-2 uninfected participants. Results A 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. Conclusions The 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)

INSPIRE II: clinicaltrials.gov (NCT01190111) and INSPIRE III: EudraCT (No. 2010-019773-15) and clinicaltrials.gov (NCT01241643).

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and the *Bacteriology Laboratory, Bradford Royal Infirmary, Bradford SUMMARY Faeces or rectal swabs from 1527 subjects were examined for the presence of intestinal spirochaetes by anaerobic culture on blood agar incorporating spectinomycin (400 mg/l). Twenty three specimens (1-5%) were positive, and only one of these came from a patient with diarrhoea. All positive specimens came from either Asians or known homosexuals. Comparative tests showed a close phenotypic similarity between the human isolates and non-pathogenic porcine intestinal spirochaetes. These organisms differ from Brachyspira aalborgi, a spirochaete isolated from subjects with histologically confirmed intestinal spirochaetosis.Organisms similar to spirochaetes were first observed in faeces, using the light microscope, towards the end of the last century.' Associations were noted with cholera, dysentery, and other intestinal conditions, but later studies described the presence of spirochaetes in the faeces of normal healthy subjects, and similar organisms were found in the intestinal tracts of various animal species.2 A wide variation was noted in the incidence of spiral organisms in specimens collected in different geographical areas.2 4 Further interest was stimulated by the advent of electron microscopy. True spirochaetes with axial fibrils were shown in the intestinal tracts of man and animals.5