Experts encouraged by COVID-19 vaccine data but get ‘wakeup call’ from variants
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Experts were encouraged by new efficacy data from COVID-19 vaccine trials conducted in the United Kingdom, South Africa and elsewhere, even as they raised questions about the impact of SARS-CoV-2 variants.
“We’re learning not only that we have more vaccines, but we’re learning about the virus and how it interacts with our ability to protect with vaccines,” National Institute of Allergy and Infectious Diseases Director Anthony S. Fauci, MD, said during a White House briefing on the COVID-19 response.
Following the authorization of two COVID-19 vaccines in the United States — both messenger RNA (mRNA)-based vaccines developed by Pfizer-BioNTech and Moderna, which demonstrated better than 90% efficacy in phase 3 trials — attention turned toward other vaccines in development, namely two products developed by Novavax and Johnson & Johnson.
Both companies publicized clinical trial results of their vaccines in late January.
Novavax said its protein-based vaccine candidate, NVX-CoV2373, was nearly 90% efficacious in a phase 3 clinical trial in the U.K., during which most cases were attributed to the emerging B.1.1.7 variant, which has been widely reported in the U.S.
However, results of a phase 2b study in South Africa showed the vaccine was 60% efficacious (95% CI, 19.9%-80.1%) at preventing mild, moderate and severe cases among HIV-negative participants in that country, and 49% efficacious (95% CI, 6.1%-72.8%) when both HIV-positive and HIV-negative participants were included.
According to Novavax, more than 90% of cases during the South African trial were attributable to the B.1.351 variant, which has raised concerns over its ability to evade vaccines and therapies.
The variant was reported in the U.S. for the first time in January — first in two patients in South Carolina who were not epidemiologically linked and had no travel history, according to CDC Director Rochelle P. Walensky, MD, MPH, and then in Maryland.
Johnson & Johnson said its one-shot vaccine candidate was 85% efficacious at preventing severe disease in a phase 3 trial being conducted in eight countries, and 66% efficacious overall at preventing moderate to severe disease.
In a press release, the company reported that the vaccine’s efficacy was 72% in the United States, 66% in Latin America and 57% in South Africa, where 95% of COVID-19 cases that occurred during the trial were from the B.1.351 variant.
‘Very encouraging’ results
Fauci characterized the results of the trials as “really very encouraging” because they showed virtually no hospitalizations or death in the vaccination arms.
In particular, he said the Johnson & Johnson results demonstrated that there is at least a third viable vaccine candidate for the U.S. — one that is given in one dose, is less expensive and does not require the cold chain management of the other vaccines.
The vaccinee can be kept for 2 years at –4°F, including at least 3 months at a normal refrigeration temperature of 36°F to 46°F, unlike some of the other vaccines, which require extremely cold storage.
“Even though the long-range effect in the sense of severe disease is still handled reasonably well by the vaccines, this is a wakeup call to all of us that we ... will continue to see the evolution of mutants,” Fauci said on another teleconference with reporters, adding that manufacturers can continue to make versions of the vaccines to address the mutants.
The takeaway, Fauci suggested, is that the vaccines — even if they do not have a 95% overall efficacy, as the first two messenger RNA vaccines approved in the U.S. did — have demonstrated a “profoundly positive effect” on diminishing advanced disease and hospitalization from COVID-19, even though the overall effect of the vaccine is diminished.
The variant first identified in the U.K., which CDC scientists have predicted will become the dominant SARS-CoV-2 virus in the U.S. by March, had “little impact” in a trial assessing the efficacy of the Novavax vaccine, said Fauci, who is also the White House’s chief medical advisor on COVID-19.
The variant first reported in South Africa demonstrated that “antigenic variation does have clinical consequences,” Fauci said, although the findings from the Johnson & Johnson trial showed that immunization with that vaccine “was still within the cushion level of providing some protection.”
Scientists in South Africa said tests showed that the variant first reported in that country “is largely resistant to neutralizing antibodies elicited by infection with previously circulating lineages.”
“This suggests that, despite the many people who have already been infected with SARS-CoV-2 globally and are presumed to have accumulated some level of immunity, new variants ... pose a significant reinfection risk,” the scientists wrote in a non-peer-reviewed paper that was published on the preprint server bioRxiv.
Moreover, they said the findings “may foreshadow reduced efficacy of current spike-based vaccines.”
During an Infectious Diseases Society of America press briefing, Kathryn Edwards, MD, who heads the Vanderbilt Vaccine Research Program, said some tests have been modified because of mutations in the virus’ spike protein.
“We will be evolving and responding to these issues,” she said.
Pfizer and Moderna have both reported the results of laboratory tests which showed that their vaccines appear to be protective against emerging variants. Still, Moderna reported that, out of “an abundance of caution,” it would launch a clinical program to boost immunity to the emerging variants and will test an additional booster dose of the vaccine to study the possibility of increasing the neutralizing titers against emerging strains beyond the existing primary vaccination series.
Currently, the Moderna vaccine is given in two doses 28 days apart. The Pfizer vaccine is administered in two doses 21 days apart.
“We continue to remain concerned about the emergence of variants in the United States and are rapidly ramping up surveillance and sequencing activities as we work to closely monitor and identify variants as they emerge,” Walensky said during a White House briefing.
“We know viruses mutate, and they tend to mutate in ways that are advantageous to the virus. We expected this,” she said, reiterating that the emergence of variants underscores the need to be “steadfast” in prevention measures such as wearing masks and avoiding crowds.
‘Get vaccinated’
Walensky said there were more than 90,000 deaths from COVID-19 in January — the most in any month of the pandemic. U.S. deaths approached a half-million in the early days of February, as the case count climbed above 26 million — more than a quarter of global cases, according to tracking by Johns Hopkins University.
As of Jan. 31, there were nearly 500 cases of COVID-19 in the U.S. that were attributed to one of several emerging variants, mostly the U.K. variant. In addition to the cases of the variant first identified in South Africa, there also was at least one case of a variant first reported in Brazil, which was recorded in Minnesota.
The U.K. variant, which has been reported to be more transmissible than the wild-type SARS-CoV-2 virus, will become the predominant SARS-CoV-2 variant circulating in the U.S. by March, according to a report by CDC researchers that was published in MMWR, which warned that the emergence of the variant could “threaten strained health care resources, require extended and more rigorous implementation of public health strategies, and increase the percentage of population immunity required for pandemic control.”
Fauci said the best countermeasure to the emergence of variants in the U.S. and globally is already available.
“You need to get vaccinated when it becomes available as quickly as possible, because viruses cannot mutate if they do not replicate,” Fauci said. “If you stop their replication by vaccinating widely and not giving the virus an open playing field to continue to respond to the pressures that you put on it, you will not get mutations.”
- References:
- Galloway SE, et al. MMWR Morbid Mortal Wkly Rep. 2021;doi:10.15585/mmwr.mm7003e2.
- Wibmer CK, et al. bioRxiv. 2021;doi:10.1101/2021.01.18.427166.
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