First in Class “Semi-Live” RNA Vaccines against SARS-CoV-2, RSV and other Respiratory Viruses

Background

Lower Respiratory Tract Infections (LRTI) induced by Corona (SARS-CoV-2, SARS-CoV, MERS-CoV) or Para-influenza (RSV) viruses, pandemic strains of Influenza virus, and others often result in severe and life threatening conditions. Despite support by respiratory ventilation, extracorporeal membrane oxygenation (ECMO) and multiple supportive actions many hundred thousand of patients die each year. These respiratory viruses attach to, enter and destroy lung cells thereby causing airway destruction and high-grade bronchial inflammation. In this way, oxygen up-take in the lungs is severely impaired, which often is exacerbated by an immuno-pathological cytokine release syndrome (CRS).

Unfortunately, current approaches do NOT block the most important initial step of respiratory infections, i.e. viral attachment to mucosal cells and therefore have to be considered as non-protective; e.g., all anti-RSV vaccine approaches developed so far are “only” able to induce systemic, but not mucosal antibody responses and therefore have failed.

For this reason, “vir4vac” has set out a novel concept ensuring full mucosal protection by fully abrogating all initial contacts of respiratory viruses to the respiratory tract and lung cells ().

Technology Overview

Scientists from the MPI of Biochemistry in Martinsried have generated Sendai virus “Semi-live” RNA Vaccines (the “vir4vac” platform) which are characterized by highest safety features ensured by a full replication deficiency of the vaccine vectors, which guarantees prevention of any uncontrolled spread, amplification, persistence and potential mutations of these recombinant vaccines within vaccinated people.

This RNA-Vectored “Semi-live” Vaccines mimic the natural viral infection process of all respiratory viruses (see Figure above) and thereby achieves protection directly in the airways (via simple intranasal application of this safe RNA-Vectored Vaccines).

Current “vir4vac” Projects:

• PoC of the “vir4vac” platform was demonstrated pre-clinically with a vaccine candidate encoding the RSV-F protein. Efficient mucosal (and systemic) antibody responses and protection against challenge infections could be achieved. This RSV vaccine candidate is now ready for a phase I clinical trial.
• Based on the well-characterized “vir4vac” vector platform, Max Planck researchers are now also setting out to develop comparable vaccine candidates against the actual pandemic SARS-CoV-2 virus.

In summary, this novel first-in-class, intra-nasally applicable, safe recombinant “vir4vac” RNA vaccines constitute a very safe and efficacious way of preventing serious infections of respiratory corona and paramyxoviruses as well as other respiratory viruses.

Further Details

1. Stahlmann R, Lode H: Medication for COVID-19, an overview of approaches currently under study. Dtsch Arztebl Int 2020; 117: 213-9.DOI: 10.3238/arztebl.2020.0213 ( review on current vaccination approaches)
2. Wiegand MA, Gori-Savellini G, Gandolfo C, Papa G, Kaufmann C, Felder E, Ginori A, Disanto MG, Spina D, Cusi MG. Repiratory syncytial virus (RSV) vaccine vectored by a stable chimeric and replication-deficient Sendai virus protects mice without inducing enhanced disease. J Virol 2017; Apr 28;91(10).
3. Sealy RE, Surman SL, Hurwitz JL. CD4+ T cells support establishment of RSV-specific IgG and IgA antibody secreting cells in the upper and lower murine respiratory tract following RSV infection. Vaccine 2017; May 9;35(20):2617-2621. Doi:10.1016/j.vaccine.2017.03.073.
4. Wiegand M, Neubert WJ. Sendai Virus Vector: Advantages and Applications. Genome replication-incompetent Sendai virus vaccine vector against respiratory viral infections (Chapter 4: 91-126). Y Nagai (ed.), Springer Japan 2013. ISBN 978-4-431-54556-9 (eBook).
5. Wiegand M, Gori-Savellini G, Martorelli B, Bossow S, Neubert WJ, Cusi MG. Evaluation of a novel immunogenic vaccine platform based on a genome replication-deficient Sendai vector. Vaccine 2013; 31(37):3888-93.

Benefits

Further superior characteristics of these unique “SEMI-LIVE” Sendai virus vectors are

1. absence of any preformed anti-vector immunity or pre-immunity in humans
2. simple non-traumatic mucosal administration (≠ syringe for kids; see Figure 1), and
3. scalable manufacturing due to cell culture-based production platform (independence from eggs or animals)

Opportunity

Max Planck Innovation are now looking for either an investor and/or a licensing partner for this technology who is interested in the further clinical development of this state-of-the-art “Semi-live” RNA vaccine platform. Max Planck Innovation will be very pleased to share detailed information and scientific data.