Intranasal vaccine eliminates Covid-19 in mice

A team of Higher Council for Scientific Research (CSIC) has developed a novel intranasal vaccine which allows the SARS-CoV-2 virus to be eliminated in mice, “completely” blocking the infection and preventing its replication in the body, even in the most recent variants.

The essay, published in the magazine Proceedings of the National Academy of Sciences, has demonstrated the safety of these experimental vaccines and their effectiveness by producing sterilizing immunity in rodents genetically modified to have characteristics of the human immune system, based on RNA replicons from the Covid-19 virus.

“These replicons lack six important genes for viral pathogenesis and propagation, they can multiply inside the cell, amplifying more than a thousand times, they form particles similar to real viruses, but they are incapable of leaving and infecting other cells,” explained the research leader and member of the National Center for Biotechnology of the CSIC, Luis Enjuanes.

By eliminating several of the virus genes that contributed to its virulence, the replicons generated are “especially safe” as vaccines and, as several viral proteins are expressed beyond the S protein (the spike protein of SARS-CoV-2), multiple types of immune system defenses are activated, including antibodies, T cells and immunological memory.

“While with a single dose the protection in mice reaches 60 percent, the use of a double immunization intranasally reaches 100 percent protection against SARS-CoV-2 infection. Furthermore, the undetectable levels of virus in the nasal and lung samples indicate that immunization is sterilizing,” added Enjuanes.

The research team has pointed out that this intranasal system offers several advantages, such as the ability of the replicon to copy itself inside the cell, which would allow reduce vaccine dose necessary; either its ability to achieve greater induction of the immune response by containing different viral antigens and manages to block the infection in the nasal mucosa.

The vaccine acts directly on the respiratory mucous membranes

Likewise, he highlighted that this type of administration acts directly on the respiratory mucous membranes, the gateway of the virus to the bodywhich generates a “powerful” local response. Being a non-invasive and more comfortable route, it could also be easier to use in mass vaccination campaigns or in vulnerable people.

The vaccine has also induced robust activation of T cells (CD4+, CD8+), neutralizing antibodies against virus variants, and immunological memory cells.

Among its main benefits are also the production of several viral proteins that activate different types of defenses; and its multiplication within cells, which allows lower doses to be used.

The aforementioned replicons have been tested both in vitro to choose those that produced a high amount of particles similar to real viruses, with a low inflammatory response, and then test them in models in vivo. Besides, versions of the replicons have been included against the initial variants of the virus (Wuhan) and against the XBB.1.5 variant, which is currently used in commercial vaccines.

The effectiveness of each replicon is specific to the variant that causes the infection, so adaptation of the sequence to the variant circulating at all times would be necessary, although the researchers have stated that this update would be “easily doable” in two or three months.

All of this could result especially beneficial for older peoplea population group that usually shows weaker responses to conventional vaccines.

“The effectiveness of current vaccines among older people is limited. “The immune responses generated in this group after receiving current messenger RNA vaccines tend to be weaker,” the researchers concluded.