The Next Likely COVID-19 Vaccine Has Its Advantages – Medscape

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Among the multiple vaccine candidates around the globe, next up in the arsenal against COVID-19 is likely the single-dose Ad26.COV2.S vaccine in development from Johnson & Johnson/Janssen, infectious disease experts predict.

And it got closer this week with promising interim phase 1/2a trial results, published online January 13 in The New England Journal of Medicine.

A single Ad26.COV2.S dose was associated with S-binding and neutralizing antibodies in more than 90% of the participants. The finding was observed in both adults age 18-55 years and participants 65 and older, as well as for participants given low-dose or high-dose vaccinations.

The results also suggest a durable vaccine response. "The take-home message [includes] a high neutralizing antibody responder rate to a single dose of our Ad26.COV2.S COVID-19 vaccine candidate. In addition, we see that these responses and antibody titers are stable for at least 71 days," senior study author Hanneke Schuitemaker, PhD, global head of viral vaccine discovery and translational medicine at Johnson & Johnson in Leiden, the Netherlands, told Medscape Medical News.

If the single-dose Johnson & Johnson product gains FDA emergency use authorization (EUA), it could significantly boost the number of overall immunizations available. Less stringent storage requirements only regular refrigeration vs a need to freeze the Pfizer/BioNTech and Moderna COVID-19 vaccines is another potential advantage. The Ad26.COV2.S vaccine can be refrigerated for up to 3 months at 36-46 F (2-8 C).

"Phase 1-2 trial data on the J&J vaccine. If it works as well as the mRNA options, it will have substantial advantages," Jeremy Faust, MD, an emergency room physician affiliated with Brigham & Women's Hospital and Harvard Medical School, tweeted on January 13.

Unlike the Pfizer/BioNTech and Moderna messenger RNA vaccines, the Johnson & Johnson product is a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike (S) protein.

Under normal circumstances, phase 3 trial results would not be anticipated within weeks of phase 1/2a trial findings. However, the urgency of the COVID-19 pandemic accelerated the vaccine development process, so preclinical trials were conducted simultaneously and not sequentially. For this reason, phase 3 interim results for the Johnson & Johnson vaccine are expected within weeks, and a company executive told Reuters that the rollout is on track for March.

"We hope to report data from our first phase 3 study, ENSEMBLE, in which we are testing the protective efficacy of a single dose of Ad26.COV2.S, by the end of this month or early February," Schuitemaker said.

In the meantime, the phase 1/2a ongoing, multicenter, randomized, double-blind, and placebo-controlled trial interim results have drawn positive reactions.

"Data is highly encouraging and supports the single inoculation approach that makes this vaccine unique," Carlos del Rio, executive associate dean for Emory University at Grady in Atlanta, Georgia, wrote in a tweet on January 13.

"Encouraging COVID vaccine data from J&J published today. Solid antibody, CD4 T cell, and CD8 T cell responses a nice trifecta of vaccine immune responses to see! And safe!" tweeted Shane Crotty, PhD, vaccine scientist and professor at the La Jolla Institute for Immunology in La Jolla, California.

At baseline for the phase 1/2a trial, 2% of the younger group and 1% of the 65+ group were seropositive for SARS-CoV-2 S-specific antibodies.

A total of 402 people in the younger age cohort and 403 in the 65 and older group received a first dose of the Johnson & Johnson vaccine. Many participants also received a second dose 56 days later for a separate trial, ENSEMBLE2, designed to compare safety and efficacy between single- and double-dose regimens. Results of that trial are still pending.

A single dose was associated with a higher incidence of solicited systemic adverse events in the higher vaccine dose group. They also found that grade 3 adverse events decreased with increasing age.

Injection site pain on the day of immunization or the next day was the most common local reaction. The pain generally resolved within 24 hours. Fever was reported by 15% of the low-dose vaccine group and 39% of the high-dose cohort. Fatigue, headache, and myalgia were the most common grade 1 or 2 solicited systemic adverse events reported.

Five serious adverse events were reported, includingfour that investigators deemed unrelated to vaccination: hypotension, bilateral nephrolithiasis, legionella pneumonia, and one case of worsening of multiple sclerosis. The vaccine-related serious adverse event was a fever that resulted in hospitalization because of suspicion of COVID-19. The patient recovered within 12 hours.

"These data confirm our previous experience with vaccine candidates based on our Ad26 viral vector platform in the younger age group. The almost similar performance in older adults is promising," Schuitemaker said.

A potential limitation of the phase 1/2a trial is "the lack of representation of minority groups," the researchers note. Johnson & Johnson is working on improving the diversity of study participants "with respect to groups that seem to be affected most by the COVID-19 pandemic."

The AstraZeneca/Oxford AZD1222 vaccine in development received approval for use in the United Kingdom on December 30. The approval came afterPublic Health England said the country was facing "unprecedented" levels of infections, the BBC reported. AstraZeneca applied for European Medical Agency approval earlier this week, which could lead to more widespread use across Europe.

The status of the vaccine remains uncertain in the United States. A phase 3 trial in the US that started in August was paused for about 6 weeks in September and October after an adverse event in a British volunteer halted studies worldwide. On October 23, the FDA permitted researchers to continue the trial with approximately 40,000 participants.

There was some suggestion in the clinical trials that a half dose of the AstraZeneca vaccine was more effective than a full dose, 90% vs 62%, but some irregularities in the research require further investigation.

Although the AstraZeneca vaccine is delivered to cells by an adenovirus similar to the Johnson & Johnson product it is designed to be delivered in two doses 28 days apart, similar to the administration schedule of the Moderna mRNA vaccine.

Regardless of which vaccine product is next to gain an EUA in the United States, many experts agree the COVID-19 vaccine rollouts so far have been problematic, at a time when cases are climbing to record-breaking levels, and likely more related to logistics overadministration of the vaccine than production of the doses.

"Lots of doses being manufactured. In December 20 million, January 40 million, February 80 million and J&J hopefully soon to add to the count. The shortage is the number arms not getting vaccinated. Freezers do not get COVID. They do not need all those vaccines," Daniel Griffin, MD, PhD, an infectious disease expert in Port Washington, New York, tweeted on January 12.

"Unfortunately, the rollout has not gone smoothly, partly due to a lack of resources for this distribution phase we're in," said Andrew T. Pavia, MD, chief of the Division of Pediatric Infectious Diseases of University of Utah School of Medicine in Salt Lake City, during amedia briefing today sponsored by the Infectious Diseases Society of America (IDSA).

"We're concerned about the mismatch between the number of people who are being told they are eligible and the amount of vaccine that is being distributed," he said.

Complicating the rollout is a directive from US Health and Human Services Secretary Alex Azar that states should start vaccinating everyone 65 and older as well as those with underlying conditions.

Expanding distribution to the 15% of Americans in just this age group is a big challenge, Pavia said. "We have enough vaccine maybe to vaccinate 40 million by the end of this month. There is a huge disconnect, and that creates a lot of problems."

"One of the biggest problems is we are trying to do this mass vaccination program in the middle of the biggest surge we've ever seen," Julie Vaishampayan, MD, MPH, chair of the IDSA Public Health Committee, said during the briefing. Without sufficient time for public health officials to plan for vaccinating a larger population, "people will come and stand in extremely long lines."

Trying to expand immunization access without a proportionate increase in available doses prompted Vaishampayan to share an analogy from a colleague: "We are trying to fill a lake with a garden hose. Rather than making the lake bigger, what we really need is more water."

Pavia emphasized that infectious disease experts "know the measures that work." Not using masks, physical distancing and hand hygiene, he said, "is a bit like knowing that really good shark repellents will be available in summer, so I'm going to jump into the ocean covered in blood while the great whites are swimming around."

An official at the World Health Organization (WHO) agreed. "Vaccines are coming online and I do believe vaccines will make a huge difference. But they are not here yet in enough quantities and in enough people to make that difference," said Michael Ryan, WHO executive director of health emergencies during an online media briefing January 13, held in conjunction with Emory University.

Ryan predicted that "we've got weeks if not months ahead of us in which our weapon is our knowledgewhat we know about this virus, its transmission, and stopping that transmission."

"And as the vaccines roll in, we can hopefully end this horrific pandemic."

Schuitemaker reports grants from BARDAduring the conduct of the study; personal fees and other from Janssen Vaccines and Prevention, a J&J company, outside the submitted work. Johnson & Johnson and the Biomedical Advanced Research and Development Authority of the Department of Health and Human Services funded the phase 1/2a study.

N Engl J Med. Published online January 13, 2021. Full text

Damian McNamarais astaffjournalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology and critical care.Follow Damian on Twitter: @MedReporter.

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The Next Likely COVID-19 Vaccine Has Its Advantages - Medscape