Intravacc announces vaccine candidates for RSV, gonorrhoea

Intravacc, a Netherlands-based developer of viral and bacterial vaccines, has published the phase I study results of its vaccine candidate for respiratory syncytial virus (RSV) — a major cause of lower respiratory tract infections and the most common cold virus in children under the age of five. In general, the virus causes mild complaints; however, infants and the elderly can become seriously ill.

Yet despite many biotech and pharmaceutical companies having attempted the development of a vaccine since the 1960s, there is currently still no effective approved treatment for persistent RSV infections. Passive immunisation with humanised F-specific monoclonal antibodies (palivizumab) is limited to high-risk infants, and its use is mainly reserved for high-income countries due to its high cost. As a result, an estimated 120,000 children worldwide die of the virus every year — especially in developing countries.

“Worldwide, RSV is estimated to be the second cause of death after malaria in infants aged one to 12 months due to a single pathogen,” said Intravacc CEO Dr Jan Groen. “By the age of two, almost all infants have been exposed to RSV. However, immunity to RSV is incomplete and reinfections are common throughout life. A solution in the form of a vaccine therefore meets a great unmet medical need.”

Using reverse genetics, Intravacc constructed a live attenuated vaccine against RSV from which the coding sequence for the attachment protein (G) was removed from the RSV genome (RSVΔG). Live attenuated vaccines can be administered intranasally, mimicking the natural route of infection and thereby stimulating both local mucosal and systemic immunity. In preclinical studies, RSVΔG showed decreased host cell binding and infectivity. Intranasal immunisation of laboratory animals with the RSVΔG vaccine protected against replication of wild-type RSV, without aggravating the disease.

As described in the journal Vaccine, the company’s phase I study saw healthy adult volunteers (18–50 years) receive either one intranasal dose of vaccine or a placebo. The vaccine was said to show excellent induction of immunogenicity, with no measurable amounts of vaccine excreted after administration, indicating sufficient attenuation of the vaccine. The live attenuated vaccine also appeared to be safe and well tolerated, with side effects that were mild and comparable to the placebo group.

Since almost everyone is infected with the RSV almost every year, adults have a fairly high background immunity. That makes it difficult to evaluate efficacy in this group. Measured antibody levels were comparable before and after immunisation and between vaccine and placebo groups. In a subsequent study it must be demonstrated whether the vaccine is immunogenic to children; Intravacc is currently orienting on a suitable partner for further joint clinical development of this vaccine in a large paediatric setting.

“Although the development of an RSV vaccine is very complex, our live attenuated vaccine provides an important first step in the clinical development of an ultimately effective vaccine,” Dr Groen said. “We look forward to working with targeted industry partners for the further joint development of this promising vaccine.”

Meanwhile, Intravacc has separately announced a partnership with US biotech company Therapyx to further develop and optimise the world’s first prophylactic vaccine against gonorrhoea, NGoXIM. Therapyx received a $2.8 million Phase IIB grant for the vaccine and chose to partner with Intravacc for its capabilities and infrastructure for the optimisation of vaccines, vaccine processes and vaccine technologies.

Gonorrhoea is the second most common bacterial infectious disease in the US, with a reported incidence of more than 300,000 cases per year. There is currently no effective gonorrhoea vaccine available and the sexually transmitted disease is known to be contracted repeatedly, without apparently developing protective immunity as a result of previous infection. In addition, antibiotic resistance is increasingly common for the Neisseria gonorrhoeae bacterium.

NGoXIM is a microsphere vaccine with encapsulated interleukin-12 (IL-12) and outer bacterial membrane vesicles from Neisseria gonorrhoeae, developed with Intravacc’s OMV platform. The vaccine therefore consists of a combination of adjuvant and antigen, specifically designed for mucosal immunisation. Vaccination with NGoXIM has been shown to induce potent and persistent antibacterial activity in primates.

The collaborators will focus on enhancing and optimising the specific adaptive immune response in non-human primates as a prelude to testing in humans. This should ultimately lead to a vaccine that provides lasting protection against infection with Neisseria gonorrhoeae.

“We are proud to partner with Therapyx in the further optimisation and development of the world’s first gonorrhea vaccine,” Dr Groen said. “Vaccination with the candidate vaccine inducing a potent and lasting antibacterial activity in primates not only shows the proof of principle for NGoXIM, but also the potency of the mucosal vaccine platform in general.

“This rapidly adaptable platform for the engineering and development of mucosal vaccines has enormous potential for challenging respiratory viral infections, including influenza and COVID-19, among others. With our unique infrastructure and pilot plant for the optimisation of vaccines, vaccine processes and vaccine technologies, we can contribute to accelerated further development of this promising vaccine, for which there is a great worldwide medical need.”

Image credit: ©stock.adobe.com/au/zilvergolf

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