Monkey rechallenge data provide COVID-19 neutralizing antibody benchmark for vaccine developers
As IMV and Vaxart prepare to advance their COVID-19 vaccine candidates into the clinic, monkey data from a Harvard-led team provide not only evidence of protective immunity following COVID-19 resolution, but also an antibody benchmark for vaccine developers to meet or beat.
At least two COVID-19 vaccine developers have reported neutralizing antibody titers from immunized non-human primates: Sinovac Biotech Ltd. (NASDAQ:SVA) for PiCoVacc; and the University of Oxford for AZD1222 (formerly ChAdOx1 nCoV-19), which AstraZeneca plc (LSE:AZN; NYSE:AZN) licensed on April 30. Sinovac reported prechallenge mean neutralizing titers of 50 in a high dose group and 61 in a medium dose group; Oxford reported titers of 5-40 (see “Comparing Monkey Data” and “With AZ Deal, Operation Warp Speed Takes First Step”).
On Wednesday in Science, a group led by scientists at Harvard Medical School’s Beth Israel Deaconess Medical Center showed that nine rhesus macaques that had recovered from mild COVID-19 had neutralizing antibodies at titers of about 100 on day 35 after intranasal and intratracheal infection. Despite challenge with different SARS-CoV-2 doses -- 11,000, 110,000 or 1.1 million plaque-forming units -- titers were consistent across the monkey cohorts and ranged from 35-326 in a live virus neutralization assay and 83-197 in a pseudovirus neutralization assay.
The researchers also showed the monkeys had generated antispike CD4+ and CD8+ T cell responses, with a trend toward less reactivity in animals that had been infected with the lower viral doses.
Demonstrating protection from reinfection, the same nine monkeys exhibited a >10-fold boost in neutralizing antibody titers following rechallenge with initial infection doses 35 days after the first viral exposure.
Median peak viral RNA levels were more than 100,000 times lower in lung fluid during reinfection than initial infection; and more than 50 times lower in nasal samples. Moreover, across 14 days the monkeys had fewer symptomatic days and lower clinical scores after rechallenge compared with primary infection.
Separately, IMV Inc. (TSX:IMV; NASDAQ:IMV) and Vaxart Inc. (NASDAQ:VXRT) announced the selection of their clinical COVID-19 vaccines; and CanSino Biologics Inc. (HKEX:6185) and Precision NanoSystems Inc. partnered to develop an mRNA-lipid nanoparticle candidate. Precision will use its platform to formulate the vaccine and CanSino will be responsible for preclinical and clinical testing, regulatory approval and commercialization.
IMV plans to begin this summer a Canadian Phase I trial of DPX-COVID-19, which comprises multiple peptide antigens formulated within its DPX platform for lipid-based delivery.
Vaxart is slated to begin Phase I testing next half of its oral vaccine candidate from its adenovirus serotype 5 (Ad5)-based VAAST platform, and on Wednesday named Kindred Biosciences Inc. (NASDAQ:KIN) as its second vaccine manufacturing partner. Vaxart is also partnered with Emergent BioSolutions Inc. (NYSE:EBS) on COVID-19 vaccine manufacturing.