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Product Development

Inovio COVID vaccine leans toward T cell responses: Data Byte 

Dec 29, 2020 | 2:22 AM GMT

Phase I data for Inovio’s COVID-19 vaccine suggest INO-4800 may stimulate T cell responses more potently than neutralizing responses. The preliminary readout also provided evidence the DNA vaccine induces both CD4+ and CD8+ memory T cell responses.

The company, which announced the data Thursday, ticked up $0.19 to $10.07 Thursday before giving back the gains on Monday, when its shares fell $0.66 to $9.60. 

The tepid market reception suggests that, as in June when shares of Inovio Pharmaceuticals Inc. (NASDAQ:INO) lost 15% with the announcement of “overall immune responses” in 94% of trial participants at week six that investors see neutralization titers as the key benchmark of COVID-19 immunity.

The data, published on Dec. 24 in EClinicalMedicine, show prime-boost administration of 2 µg INO-4800 led to strong T cell responses against the SARS-CoV-2 spike protein at week eight vs. baseline in all 19 evaluable subjects, and induced neutralizing antibodies in 16 (84%) of them.

The study also evaluated prime-boost administration of 1 µg INO-4800. The lower dose led to lower humoral and cellular response rates but higher neutralization titers than the 2 µg dose. 

With a single exception, all trial participants produced either detectable neutralizing antibodies, detectable T cell responses or both. The one individual who generated neither response was in the low dose group.

Further characterization of volunteers’ T cell responses revealed that the proportions of anti-spike CD8+  T cells were balanced between effector, effector memory and central memory cells. Anti-spike CD4+  T cells predominantly had a central memory phenotype.

The assumption that humoral immunity will be key to protection from SARS-CoV-2 gained more traction via a Dec. 22 bioRxiv paper from Yale University’s Akiko Iwasaki and colleagues linking early generation of neutralizing responses with better patient outcomes.

Patients who produced neutralizing antibodies within 14 days of symptom onset were more like to clinically improve and survive than those who produced antibodies after that time window. 

Although the role of T cells in protecting against COVID-19 has been studied far less,  at least one non-human primate study has shown that robust antiviral CD8+ T cell responses can compensate for weak humoral immunity, indicating the T cell responses induced by Inovio’s vaccine may protect individuals who failed to mount a strong antibody response.

INO-4800 does have an advantage over COVID-19 vaccines that require storage at very cold temperatures: the intradermal vaccine is stable at 37° C for over a month and at room temperature for over a year. It has an expected 5-year shelf-life at normal refrigeration temperatures of 2-8° C, according to the company.

Another candidate that is stable at 2-8° C is NVX-CoV2373 from Novavax Inc. (NASDAQ:NVAX). The biotech announced Monday the start of the U.S. and Mexican Phase III PREVENT-19 trial testing intramuscular prime-boost administration of NVX-CoV2373 in up to 30,000 subjects. The primary endpoint of the placebo-controlled study is prevention of symptomatic COVID-19.

According to the complete protocol, the pivotal trial’s final analysis is expected to occur at 144 events; interim analyses are planned to occur when 50% and 75% of 144 events have accrued. A representative for Novavax told BioCentury the company cannot predict when it will have the data needed to apply for emergency use authorization; timing will depend on factors including enrollment speed and epidemiology.

Novavax, whose vaccine’s timeline is behind that of several others, lost $12.49 (10%) to $116.85 Monday.

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