Neutralizing antibodies correlate with protection from SARS-CoV-2 in humans during a fishery vessel outbreak with high attack rate

Abstract

The development of vaccines against SARS-CoV-2 would be greatly facilitated by the identification of immunological correlates of protection in humans. However, to date, studies on protective immunity have only been performed in animal models and correlates of protection have not been established in humans. Here, we describe an outbreak of SARS-CoV-2 on a fishing vessel associated with a high attack rate. Predeparture serological and viral RT-PCR testing along with repeat testing after return to shore was available for 120 of the 122 persons on board over a median follow-up of 32.5 days (range 18.8 to 50.5 days). A total of 104 individuals had an RT-PCR positive viral test with Ct <35 or seroconverted during the follow-up period, yielding an attack rate on board of 85.2% (104/122 individuals). Metagenomic sequencing of 39 viral genomes suggested the outbreak originated largely from a single viral clade. Only three crewmembers tested seropositive prior to the boat's departure in initial serological screening and also had neutralizing and spike-reactive antibodies in follow-up assays. None of these crewmembers with neutralizing antibody titers showed evidence of bona fide viral infection or experienced any symptoms during the viral outbreak. Therefore, the presence of neutralizing antibodies from prior infection was significantly associated with protection against re-infection (Fisher's exact test, p=0.002).

Figure 1 –

Pre-departure serological assays. A) Abbott Architect index values for all 120 individuals assayed. The grey line indicates the cutoff for a positive Abbott reading (≥ 1.40). Individuals with negative Abbott index values are further classified by whether they subsequently became infected on the ship. Individuals with positive Abbott index values are further characterized by whether their pre-boarding serum was neutralizing. B) Neutralization curves for all 6 pre-boarding samples that were positive in the Abbott Architect assay. C) Titers of RBD- or Spike-binding IgG antibodies in all 6 Abbott positive pre-boarding samples as measured by ELISA. The negative control sample is pooled sera collected in 2017–2018 from 75 individuals (Gemini Biosciences, 100–110, lot H86W03J).

Figure 2 –

Return to shore testing. A) Abbott Architect SARS-CoV-2 index values over time (pre- and post-departure) are depicted for each individual with at least 2 serum draws. The dashed line denotes the seropositivity cutoff of the assay (1.40). Individuals who had a positive RT-PCR with Ct < 35 or who seroconverted during the follow-up period are shown in light blue. Individuals who were not infected by the above case definition criteria are shown in green. Individuals who screened positive by the Abbott Architect SARS-CoV-2 IgG assay but lacked neutralizing antibodies and were infected are shown in brown. Individuals who had pre-existing neutralizing antibodies and were not infected are shown in blue. B) SARS-CoV-2 whole genome sequencing of cases from the fishery vessel confirms outbreak. SARS-CoV-2 genomes from 39 cases with Ct < 26 were recovered and a phylogenetic tree was made using FastTree along with 109 other isolates reflective of global diversity. 38 cases are highlighted in red with a median pairwise difference of 1 single nucleotide variant, while one outlier case from the boat is shown 260 with a red dot. Clade A strains associated with early trans-Pacific transmission are shown in purple.