Special Issue 5: Two More Vaccines Found Effective, but Less So Against New Variants

Feb 01, 2021

By Kristen Jill Abboud

Science Writer & Editor

Last week both Novavax and Johnson & Johnson reported data from Phase III trials of their COVID-19 vaccine candidates. Both were effective at preventing disease and will be valuable tools in controlling the pandemic, but the results were more nuanced than previous efficacy results for Pfizer/BioNTech’s and Moderna’s mRNA-based vaccines. This was largely because both Novavax and Johnson & Johnson tested their vaccines in the context of emerging viral variants in both the U.K. and South Africa.

The B.1.1.7 SARS-CoV-2 variant that was first identified in the U.K. is associated with increased transmissibility. Another variant, known as 501Y.V2 or B.1.351, is now predominant in South Africa. In laboratory studies, the 501Y.V2 variant has been shown to escape from neutralizing antibodies, raising concerns about how well COVID-19 vaccines will perform against this variant (see the interview with Penny Moore, below). These concerns were substantiated by the recently reported results of the Novavax and Johnson & Johnson trials.

The U.S. company Novavax reported that their protein-based vaccine was 90% effective at preventing symptomatic COVID-19 disease in its Phase III efficacy trial involving more than 15,000 volunteers in the U.K., where the B.1.1.7 variant has become predominant. Meanwhile in a Phase IIb trial of Novavax’s vaccine in South Africa, efficacy was only 49% amongst the entire study population, and 60% in volunteers who were not infected with HIV.

Results from Johnson & Johnson’s Phase III trial showed that a single shot of their human adenovirus-based vaccine developed at Janssen Pharmaceutical Companies was 66% effective at protecting against moderate to severe cases of COVID-19, and 85% effective overall in preventing severe cases of disease, including complete protection against hospitalizations and deaths from COVID-19 in all regions.

“In my view, the best news from the latest vaccine trials is that the efficacy was high against severe disease, hospitalization, and death in the Johnson & Johnson trial in South Africa,” says Marc Lipsitch, a Professor in the Department of Epidemiology at the Harvard T.H. Chan School of Public Health. “This suggests that existing vaccines can still have major effects on the most severe outcomes, even with the variant.”

However, efficacy did vary geographically. At 28 days post vaccination with the Johnson & Johnson vaccine, the efficacy was 72% in the U.S., 66% in Latin America, and 57% in South Africa. Notably, 95% of the COVID-19 cases in South Africa were due to the 501Y.V2 variant.

Although the Novavax and Johnson & Johnson vaccines were less effective against the 501Y.V2 variant, many researchers are quick to point out, that even at this level of efficacy, these vaccines could still play a significant and even vital role in controlling the pandemic. “I am encouraged that they remained partially effective, about as good as seasonal flu vaccines,” says David Montefiori, Professor and Director of the Laboratory for AIDS Vaccine Research and Development at Duke University Medical Center.

An obvious advantage of the Johnson & Johnson vaccine is that it is a single shot, and given the spread of these viral variants, accelerating the rollout of vaccines will be crucial. The company plans to seek an Emergency Use Authorization from the U.S. Food and Drug Administration early this month.

“It looks like we have two more vaccines in the armamentarium to battle this pandemic, each of which has its advantages in terms of efficacy, cost, logistics, and ease of administration,” says Jonathan Carapetis, Director at Telethon Kids Institute and an Australian pediatric physician who specializes in infectious diseases. “The announcements from Novavax and Johnson & Johnson are overall good news, but also something of a reality check.”

John Moore, Professor of microbiology and immunology at Weill Cornell Medical College, is less convinced that a single shot of Johnson & Johnson’s vaccine is enough. “The potency of the Novavax vaccine is at least on par with the two mRNA vaccines and, once approved, will become very useful. Although it also requires two doses, it can be shipped and stored at four degrees Celsius, which is beneficial,” he says. “I’m significantly less enthusiastic about the Johnson & Johnson vaccine, which is clearly weaker than the others. A second dose may overcome some of its limitations.”

Meanwhile, Moderna announced that laboratory studies indicate that its two-shot mRNA vaccine induced six-fold lower levels of neutralizing antibodies against the B.1.351 variant. This finding prompted the company to explore strategies for enhancing immunity against B.1.351 and other emerging viral variants, even though they say the antibody levels induced by their vaccine are still likely to be protective.

Moderna will test an additional dose of its vaccine to try to boost neutralizing antibody levels in vaccinated volunteers. The company will also develop a booster candidate specifically against the B.1.351 variant. The mRNA technology that both the Moderna and Pfizer/BioNTech vaccines employ offers great flexibility, and this may prove to be an asset in the battle against COVID-19. “I believe the vaccine manufacturers will have a boost to increase protection against 501Y.V2 in the near future,” says Montefiori.

Given how the COVID-19 vaccine landscape and the virus itself are evolving, scientists are also increasingly concerned about future variants that may emerge. “My greater concern, shared by many others, is that the virus will continue to evolve to escape the vaccine more completely,” says Montefiori. “Scientists need to be monitoring and studying new variants in real time to provide an early warning and to facilitate next generation vaccines if necessary.”

Stanley Plotkin, veteran vaccine developer, Emeritus Professor of Pediatrics at the University of Pennsylvania, and founding board chair of the Human Vaccines Project, predicts routine updates to COVID-19 vaccines may be necessary. “It certainly appears that the prospect is yearly changes to vaccines or multivalent vaccines. We need a system identical to influenza, with regional labs surveying the landscape on an ongoing basis,” he says.

Carapetis agrees. “While it is important to note that both vaccines do prevent against the 501Y.V2 variant, it signals a critical need to be working now on next-generation vaccines that can be adapted to the inevitable further mutations that will be seen in SARS-CoV-2. But perhaps the most critical messages are that vaccines alone will not be a panacea—ongoing public health measures, such as those that Australia has implemented with extraordinary success, are essential—and also that we are likely to be living with this virus for many years to come.”

By Kristen Jill Abboud

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