The World Health Organization (WHO) COVID vaccine composition advisory group met to discuss the latest SARS-CoV-2 changes and impacts on the vaccine and recommended that vaccine makers drop the ancestral strain and switch to a monovalent (single-strain) vaccine that contains an XBB.1 descendant lineage such as XBB.1.5.

In other developments, the WHO said overall global cases and deaths continue to decline, but the situation still reflects a mixed picture at the regional level.

Better response needed against XBB lineages

In a statement, the advisory group said current vaccines continue to provide substantial protection against severe illness and death, but new formulations are needed to protect against symptomatic disease.

They noted that XBB descendant lineages, including XBB.1.5 and XBB.1.16, are highly immune-evasive, with XBB.1.5 as one of the variants with the highest magnitude of immune escape from neutralizing antibodies. They acknowledged, however, that vaccine efficacy (VE) estimates against circulating strains are limited, with some studies showing VE similar to BA.5 and others showing reduced VE against XBB.1 lineages.

Meanwhile, studies involving blood samples of people who had two to four mRNA vaccine doses showed substantially lower neutralization against XBB.1 lineages. But people with hybrid immunity—from both infection and vaccination—had higher antibody titers against XBB.1 viruses.

The group said there is in vitro evidence of immune imprinting—when memory B cells after initially encountering an antigen have a reduced response to new antigens. “However, based on observational epidemiological studies to date, the clinical impact remains unclear,” they wrote.

Preclinical data on XBB.1 candidate vaccines, shared confidentially by vaccine makers, showed a higher neutralizing antibody response to current subvariants compared with currently approved vaccines.

XBB.1.5 or XBB.1.16 as vaccine strains

Given that XBB.1 lineage viruses continue to predominate, the goal of new COVID formulations should be to neutralize XBB-descendent lineages, the advisory group said. They listed XBB.1.5 as an example to include, but said the XBB.1.16 could be an alternative, since the genetic and antigenic differences between the two are so small.

They had several reasons for recommending a switch to a monovalent vaccine, including that, because the index virus no longer circulates in people, it prompts—at best—very low levels of antibodies against current strains, it reduces the concentration of the new target antigen, and it may induce immune imprinting.

In April, the group set out a timeline for making new vaccine recommendations for 2023, once this month and again 6 months later.

The US Food and Drug Administration (FDA) vaccine advisory group will meet to consider COVID vaccine strain selections on June 15 for versions that will be used in the upcoming fall and winter.

Mixed global picture; continued XBB shifts

In its weekly COVID situation report today, the WHO said overall cases and deaths continued to decline over the past 4 weeks, but hot spots continue in two regions: Southeast Asia and the Western Pacific. Deaths were also up in Southeast Asia.

In the Southeast Asia region, cases continue to spike in Thailand, Indonesia, and India. And in the Western Pacific, COVID activity continues upward trends in Vietnam, the Philippines, Mongolia, and, to a lesser extent, Japan, South Korea, and Australia.

The WHO said cases are stable in Africa, but some countries reported spikes, including the Democratic Republic of the Congo, Cabo Verde, Uganda, and Mauritius.

In its snapshot of the latest Omicron subvariant activity, the WHO said that, as of the last week of April, the global proportion of XBB.1.5 declined from 51.9% to 43.8%. Meanwhile, the proportion of XBB.1.16 viruses rose from 4.9% to 11.6%.

The only other subvariants showing growth are XBB descendant lineages: XBB.1.9.1, XBB.1.9.2, and XBB.2.3.

Read more at CIDRAP – Center for Infectious Disease Research & Policy, University of Minnesota.