Two new vaccines deliver good and bad news for the pandemic

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Science‘s COVID-19 reporting is supported by the Heising-Simons Foundation

A volunteer in Soweto receives Novavax’s COVID-19 vaccine in a South African trial that showed how a mutant virus reduces vaccine efficacy.



Last week’s efficacy results from two new COVID-19 vaccines bolstered confidence that more of the world will soon be protected from the worst of the pandemic disease, but simultaneously challenged the hopes that this first generation of vaccines will offer a sturdy shield against mild and moderate symptoms.

The COVID-19 vaccines made by Novavax and Johnson & Johnson (J&J) joined six others in showing extremely good protection against severe disease and death caused by SARS-CoV-2. But the multicountry trials conducted by each company found that in some places, the efficacy of their vaccines against mild disease fell far below the 90% to 95% range reported for other vaccines. The lowest efficacy against mild disease—49% and 57%, respectively, for Novavax and J&J—was in South Africa, where almost every case of symptomatic COVID-19 is caused by a mutant of SARS-CoV-2 that can dodge antibodies triggered by natural infection or vaccine-induced immunity.

“The euphoria over the vaccines has certainly been tempered by the recent data on the new variants,” says Soumya Swaminathan, chief scientist for the World Health Organization. But she and others stress that the hope for perfection should not be the enemy of the good. Both of the new vaccines promise to prevent hospitalizations and deaths to the same degree as competitors, even against two of the most concerning viral variants.

In addition to increasing the world’s paltry supply of COVID-19 vaccines, the new options might also speed mass immunization campaigns because of a key logistical advantage: Unlike the two messenger RNA (mRNA) vaccines authorized for use in the United States, which require subzero conditions during transport, they can be stored at 2°C to 8°C—refrigerator temperature. The J&J product offers another major plus: It is the first COVID-19 vaccine shown to work with one dose rather than two.

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Company representatives and collaborating researchers revealed the new results within 16 hours of each other, in virtual press conferences and press releases that were often thin on data. First came Novavax, a small biotech firm once considered a dark horse in the COVID-19 vaccine race. In the mRNA vaccines that crossed the finish line first, a snippet of genetic code directs the recipient’s cells to produce the SARS-CoV-2 surface protein, spike. In contrast, the Novavax candidate followed a more established strategy, mixing a labmade version of the viral protein with an immune-boosting adjuvant. A trial in the United Kingdom in more than 15,000 people found the vaccine was 89.3% efficacious against mild disease.

“These are spectacular results,” says Clive Dix, chair of the U.K. Vaccine Taskforce. The vaccine also worked well against a highly transmissible SARS-CoV-2 variant, B.1.1.7, which accounted for more than half of the trial’s COVID-19 cases. But interim results from a trial in South Africa were sobering. Among the 4400 participants, the efficacy of Novavax’s vaccine plummeted to 49.4%—the first clinical evidence that a variant identified in South Africa can indeed sidestep vaccineinduced immunity to an extent, as lab evidence had suggested.

The South African trial also revealed that the variant readily evades natural immunity. Of the people in the placebo group who developed COVID-19, 30% had recovered from an earlier infection—a “really concerning” figure, says Shabir Madhi, dean of the medical school at the University of the Witwatersrand and the study’s lead investigator. “We would have expected a large percentage of the population to have developed immunity from that first exposure.”

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Still, the trial results put to rest fears that South Africa’s widespread variant might completely thwart the vaccine. “While there definitely is an impact, it’s perhaps not as bad as we all thought it might be,” says Lynn Morris, a virologist at the University of the Witwatersrand. And no one who was vaccinated died or was hospitalized, although there were only two cases of severe disease in the small trial’s placebo group. Novavax says it is now developing “bivalent” vaccines containing both the original spike and spikes altered to mimic variants of concern.

J&J reported similar bottom lines from a far larger study of its vaccine, made by its Janssen Pharmaceuticals division. The candidate, which like several two-dose COVID-19 vaccines uses a harmless adenovirus to deliver the gene for spike, was tested in 44,000 people in the United States, Latin America, and South Africa. The single-dose vaccine had an overall efficacy of 66% against symptomatic disease, rising to 85% against severe symptoms, regardless of a person’s age or underlying medical conditions, the firm said.

The vaccine’s efficacy against mild disease was 72% in the United States and 66% in Latin America, dropping to 57% in South Africa. But no one who received it anywhere required hospitalization for COVID-19 or died. “This represents a dream vaccine for a doctor,” says Glenda Gray, a co-chair of the J&J study and head of the South African Medical Research Council. In South Africa, COVID-19 now is the No. 1 cause of death, eclipsing HIV/AIDS and tuberculosis.

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J&J plans to file for emergency use authorization from the U.S. Food and Drug Administration (FDA) this week and projects it can produce 1 billion doses this year at about $10 per dose—one-sixth or less of the price of two doses of the mRNA vaccines. Novavax is discussing with FDA whether to wait for a readout from a larger efficacy trial underway in the United States, but says it can make 150 million doses per month as soon as May. It has not announced a price.

Gray and other researchers say the mRNA vaccines’ spectacular efficacy against any COVID-19 symptoms may have become a misleading benchmark for a successful vaccine given SARS-CoV-2’s evolution. Faced with mutant strains like the one in South Africa, those vaccines might not do much better than Novavax’s and J&J’s products did, they suspect. To many, solidly preventing severe disease, regardless of strain, is a significant win. “Do you want a vaccine that prevents coughs or do you want a vaccine that prevents death?” asks Lawrence Corey of the University of Washington, Seattle, who co-leads a trials network testing the J&J, Novavax, and other vaccines bankrolled by the U.S. government’s Operation Warp Speed.

And as the emerging variants show, delivering COVID-19 vaccines into more arms is urgent, and the more options, the better. “What I take away from this week,” says Nahid Bhadelia, an infectious disease physician at Boston Medical Center, “is that we have two more tools in our toolbox at a very precarious time.”

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