An experimental intranasal vaccine eliminates the COVID-19 virus in mice and is able to completely block the infection.

A novel, new-generation, intranasally administered experimental vaccine for SARS-CoV-2 ( Covid-19 ), developed by Spanish researchers, shows 100% protection with the second dose against the most recent variants of the virus , in preclinical trials with mice. The group led by virologist Luis Enjuanes, from the National Center for Biotechnology (CNB-CSIC), which publishes its results in the journal PNAS , has demonstrated its safety and efficacy.

With a single dose, protection against SARS-CoV-2 infection in mice reaches 60%, and with double immunization, it reaches 100%, the Spanish National Research Council ( CSIC ) notes in a statement. Intranasal administration allows it to act directly on the respiratory mucosa, which are the entry point for the virus, thereby generating "a potent local immune response."

Since this is a noninvasive and more convenient route of administration, it could facilitate its use in mass vaccination campaigns or in vulnerable populations. The team highlights, among other aspects, "the potential greater efficacy" in older people, a group that tends to show weaker responses to current RNA vaccines.

The vaccine candidate aims to produce several viral proteins that activate different types of defenses that multiply within cells, allowing for the use of lower doses. It is also administered through the nose, helping to generate defenses immediately upon entry of the virus. Furthermore, "the undetectable levels of virus in nasal and lung samples indicate that the immunization is sterilizing ," that is, capable of completely blocking infection, preventing the virus from replicating in the body, explain Enjuanes and her collaborators, researchers Sonia Zúñiga and Isabel Sola.

The study is "a significant advance" in the development of next-generation vaccines against COVID-19. Its safe design, its ability to generate complete immunity, its potential usefulness in older people, and its flexibility to adapt to new variants make it "a promising candidate" for future vaccination campaigns, the statement adds.

The study was conducted with rodents genetically modified to have characteristics of the human immune system , called humanized mice. The experimental vaccine is based on "defective RNA replicons" from SARS-CoV-2, which lack six important genes, Enjuanes notes.

By eliminating several genes from the original virus that contributed to its virulence, the generated replicons "are especially safe as vaccines," the note adds. Furthermore, they express several viral proteins beyond the S (the SARS-CoV-2 spike protein), enabling the activation of multiple types of immune system defenses.

The experimental vaccine induced robust activation of T cells (CD4+, CD8+), neutralizing antibodies against virus variants, and immune memory cells. All this without detecting "significant adverse effects, weight loss, or significant lung inflammation in the rodents."

Cell culture experiments allowed us to select replicons that produce a high number of virus-like particles with a low inflammatory response, and, with this selection, we began the mouse experiments. The study included versions of the replicons against both the initial virus variants (Wuhan) and the XBB.1.5 variant currently used in commercial vaccines.

The researchers observed that the efficacy of each replicon is preferentially specific to the variant causing the infection, so it would be necessary to adapt the sequence to the circulating variant at any given time, which would be "easily achievable in two or three months."