Inovio COVID-19 vaccine data highlight questions about antibody versus T cell responses

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A chilly market reception for Inovio’s Phase I COVID-19 vaccine data suggests antibody titers are the key benchmark investors are looking for. The move raises questions about how to value vaccines when the correlates of protection are still unclear.

On Tuesday, Inovio Pharmaceuticals Inc. (NASDAQ:INO) announced 34 out of 36 (94%) trial participants showed “overall immune responses” at week six following two doses of INO-4800, a DNA vaccine encoding the SARS-CoV-2 spike protein.

Inovio also said participants experienced no serious adverse events through week 8. The company plans to expand its Phase I study to include patients over 50, and to launch a Phase II/III study this summer if it gets the go-ahead from regulators. Following the news, the company’s stock dropped $4.74 (15%) to $26.95 at market close.

The company did not report neutralizing antibody titers or quantitative measures of T cell responses, but said it observed both humoral and cellular immune responses, and plans to publish the full dataset in a peer-reviewed medical journal. In a May Nature Communications study, the company published preclinical data on neutralizing antibody titers and T cell responses in mice.

The dominant hypothesis is that neutralizing antibodies will be a critical component of protection from SARS-CoV-2 infection; as a result, clinical and preclinical vaccine performance has primarily been evaluated via neutralizing antibody titers (see “Making Sense of the Deluge of COVID-19 Vaccine Data”; “Comparing Titers in NHPs”).

But Inovio has long argued that DNA vaccines have a strong capacity to induce T cell responses, and its announcement suggests it will make the case that this will be an advantage against COVID-19.

The company highlighted recent Cell and Nature studies that respectively showed T cell responses are associated with COVID-19 convalescence, and patients can recover from COVID-19 in the absence of detectable neutralizing antibody levels.

Inovio also announced its vaccine had been selected for inclusion in Operation Warp Speed’s non-human primate (NHP) study, and said INO-4800 provided “full protection” from SARS-CoV-2 replication in the lungs of mice.

Sticking out from the competition

CanSino Biologics Inc. (HKEX:6185) has provided the crispest assessment of clinical performance for a COVID-19 vaccine thus far.

In a May Lancet study, the company reported mean neutralizing titers of 34 in its high-dose group -- well below FDA’s recommended titer for convalescent plasma -- and also provided readouts of T cell responses, noting that these were muted in study participants with pre-existing antibodies against the vaccine’s Ad5 vector.

On Monday, CanSino said it received “military specially-needed drug approval” in China for its Ad5-nCoV vaccine, making it the first vaccine to be authorized for use, albeit in a limited population.

Moderna Inc. (NASDAQ:MRNA) has not disclosed the neutralization titers for its vaccine mRNA-1273; instead, it said these were similar to mean titers from convalescent plasma. However, convalescent plasma titers are highly variable, and it’s not yet clear how they relate to patients’ disease severity or levels of protection.

The market rewarded both CanSino and Moderna for their preliminary clinical data.

Following the data release, CanSino rose HK$8 to HK$222 on a day most stocks on the Hong Kong exchange tumbled, taking its market cap to HK$49.4 billion ($6.4 billion).

Moderna rose $13.31 (20%) to $80 on its data report, raised $1.3 billion in a follow-on financing that evening, and finished the week at $69, with a market cap of $25.6 billion.

Targets

SARS-CoV-2 S - SARS-CoV-2 spike protein

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