COVID-19 vaccines based on novel platforms show early promise in mice

Pfizer and BioNTech’s mRNA vaccine BNT162b2 has already become the first COVID-19 shot approved for widespread use in the Western world, with other late-stage candidates not so far behind. But researchers in the field are still moving ahead in the hopes of finding 

alternative—and possibly better—options.

Now, two teams from City of Hope and Canadian biotech Biovaxys Technology have reported positive data for their investigational COVID-19 vaccine products in animals.

The two products, based on vaccine platforms that are different from the mRNA technology, are designed to induce both antibody and T-cell immune responses. Their developers hope they will offer longer-lasting protection against COVID.

Many of the more advanced COVID vaccines, including AstraZeneca’s Oxford University-partnered AZD1222, use a viral vector to deliver the genetic information of SARS-CoV-2—the novel coronavirus that causes COVID-19. But unlike AZD1222, which uses a monkey adenovirus to perform the delivery task, the City of Hope shot, dubbed COH04S1, adopts Modified Vaccinia Ankara (MVA), which is an attenuated poxvirus that’s also frequently used as a viral vector for vaccines.

While most COVID vaccines solely target SARS-CoV-2’s spike (S) protein, COH04S1 adds another coronavirus gene for a protein called nucleocapsid (N). Both proteins are believed to facilitate immunity against the coronavirus, and the N protein “has the advantage of being more conserved than the S protein and could therefore contribute to the stimulation of broadly effective immune responses,” the researchers noted in reporting mouse data in Nature Communications.

The vaccine-induced abundant neutralizing antibodies, which could directly kill off the virus to prevent infection, the researchers said. But the team highlighted the strong T-cell response against both the virus’ S and N antigens. Based on previous observations with another coronavirus, SARS-CoV-1, T-cell responses are believed to be more durable than antibody responses.

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“Our investigational vaccine aims to address one of the challenges in combating coronavirus infections—immunity against these viruses can be short-lived, less than six months in some COVID-19 patients,” City of Hope's Don Diamond, Ph.D., the study’s co-senior author, said in a statement.

“We spurred the production of CD4 and CD8 T cells of various types, including memory T cells,” Diamond said. “These T cells can live in the blood for a longer time than antibodies and attack a pathogen should it appear at a later time.”

Encouraged by the animal results, City of Hope has launched a phase 1 clinical trial to examine if a single dose of the shot may be sufficient for triggering immune responses in humans. The trial aims to enroll at least 119 healthy participants, and a phase 2 could start in the second quarter of 2021.

Meanwhile, the German Center for Infection Research has also developed an MVA-vectored COVID candidate that targets the S protein. The center, along with several German universities, recently kicked off a phase 1 trial of the shot, dubbed MVA-SARS-2-S.

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By contrast, Biovaxys’ vaccine, dubbed BVX-0320, is based on a concept known as haptenization. It involves linking protein antigens with small molecules called haptens to make the target proteins more “visible” to the immune system.

In mouse studies, two injections of the vaccine, together with an adjuvant called QS21, elicited positive antibody response against the SARS-CoV-2 S protein in all animals except those that got the lowest of four doses, the company said Monday.

Biovaxys is still measuring the T-cell response. Based on previous experience with haptenized proteins, the company believes BVX-0320 could also induce potent T-cell activation. Once the data analysis is complete, the company expects to seek regulatory consent for a phase 1 study in humans.