BioCentury is providing this content for free given the urgent need for information about the coronavirus crisis. Further analysis can be found in our COVID-19 Resource Center. For more, sign up for our daily email.
0114 data byte JNJ covid vax
BioCentury & Flourish

Product Development

Phase I/II antibody levels support single shot for J&J COVID-19 vaccine: Data Byte

Immune responses lasted at least two months with one dose, and antibodies against the vaccine’s viral vector did not block response to a second dose 

Immune responses lasted at least two months with one dose, and antibodies against the vaccine’s viral vector did not block response to a second dose.

Jan 15, 2021 | 2:48 AM GMT

Ahead of an imminent Phase III readout for a single shot of its COVID-19 vaccine, J&J’s updated Phase I/II data show neutralizing antibodies induced by a single dose last at least 10 weeks without decline.

Wednesday’s paper by Johnson & Johnson (NYSE:JNJ) in The New England Journal of Medicine also provides some reassurance that booster shots of JNJ-78436735 will be an option if needed. A second vaccination increased neutralizing antibody titers nearly threefold, despite the fact that the first vaccination induced antibodies against the vaccine’s adenovirus serotype 26 vector.

In the trial, 18-55 year-old volunteers given a single shot of 5x1010 viral particles, the dose being tested in Phase III, had a geometric mean titer (GMT) that rose from 224 at day 29 to 310 at day 57. The titers then began to level out, but they did not diminish. At day 71, GMT was up slightly to 321.

Among about 50 individuals ages ≥65 who received the Phase III dose, the neutralizing GMT at day 29 was 277, and 96% had detectable neutralizing titers.

The data suggest that if the vaccine is found to be effective in Phase III, the protection it confers should last a minimum of 10 weeks.

That may understate the durability because it’s not yet clear what role T cells will play in the durability of the immune response. The latest day for which J&J provided T cell data was day 15, at which 60% of subjects over age 65 had spike-reactive CD4+ T cells, and 36% had spike-reactive CD8+ T cells. For subjects aged18-55, the values were 76% and 51% for  CD4+ and CD8+ T cells, respectively. 

The antibody data suggest that antivector immunity won’t hurt the efficacy of the vaccine, which has been an outstanding question for the modality of viral vector vaccines.

In early clinical trials, CanSino Biologics Inc. (HKEX:618) found that about half of subjects had preexisting immunity against the adenovirus vector used in its Ad5-nCoV vaccine, and those subjects had substantially lower antibody and T cell responses to the vaccine. 

The lower protection rate seen with two full doses, versus two half doses, of the viral vector vaccine from AstraZeneca plc (LSE:AZN; NASDAQ:AZN) and University of Oxford may also arise from antivector immunity. Giving the full dose right away may induce stronger antivector immunity than initially giving a half dose, reducing the effect of the boost.

CanSino uses a human adenovirus 5 vector; AZ-Oxford use a simian adenovirus vector.

J&J, which uses an adenovirus 26 vector, saw almost no preexisting antivector immunity in its Phase I/II trial.

Virtually all of the subjects had developed antivector antibodies by day 57 after the first dose, indicating that exposure to the vaccine induces antivector antibodies.

The antibodies against the vector did not prevent response to a booster shot. Individuals who received a second immunization at day 57 exhibited a 2.9-fold boost in titers, with non-overlapping 95% confidence intervals, two weeks later.

There was no correlation between antivector antibody levels at day 57 and anti-SARS-CoV-2 neutralization titers across all subjects — single and prime-boost  at day 71 (Spearman correlation = -0.1). 

The findings suggest that, if necessary, a booster shot could be used to enhance efficacy of J&J’s vaccine. 

It’s still too early to know how well the the single-dose regimen’s immunogenicity translates to protection — efficacy data from the Phase III ENSEMBLE trial are expected in a few weeks. J&J is also running a second Phase III trial, ENSEMBLE 2, testing two immunizations separated by eight weeks. 

The Phase I/II trial also tested single and prime-boost administration of JNJ-78436735 at twice the Phase III dose, and enrolled subjects ages ≥65. Johnson & Johnson (NYSE:JNJ) presented preliminary two- and four-week cellular and humoral immunogenicity responses from both age groups in a September medRxiv preprint.

How to gain access

Continue reading with a
two-week free trial.