CiVax™ Shows Protective Effects Against SARS-CoV-2 Variant in NHP
On September 28, 2021, Soligenix, Inc. (NASDAQ:SNGX) announced the publication of pre-clinical immunogenicity studies for CiVax™, the company’s heat-stable COVID-19 vaccine candidate (To et al., 2021). CiVax™ is composed of a recombinant pre-fusion spike subunit (based on the reference SARS-CoV-2 strain, Wuhan-Hu-1) adjuvanted with liquid or lyophilized CoVaccine HT™. Twelve cynomolgus monkeys were immunized twice with 5 (Group A, n=3) or 25 (Group B and C) μg of spike protein antigen formulated with either lyophilized (Group A and C) or liquid (Group B) CoVaccine HT™ adjuvant. Group D served as a control and received one dose of a co-lyophilized CoVaccine HT™-adjuvanted unrelated viral glycoprotein antigen. An overview of the different dosing groups and administration schedule is shown below.
The two doses of spike protein were administered three weeks apart and all macaques were then challenged with 1 x 106 TCID50 of the P.1 isolate (Gamma variant) of SARS-CoV-2 12 weeks post-boost (study week 15). The following figures show that all macaques immunized with S protein seroconverted following the boost at week 3 (one macaque from the C group seroconverted after the first dose), with peak serum IgG concentrations detected at week 5. By week 15, IgG concentrations had dropped 3.0 to 9.9-fold relative to the peak titer. Total S protein-specific IgG is shown on the lower left and neutralizing antibody titers are shown on the lower right.
To test whether the Wuhan-Hu-1 S protein could generate durable cross-variant neutralizing antibodies, a PRNT assay was performed using sera collected at week 6 and week 15 against the WA1/2020, B.1.351 (Beta), P.1 (Gamma), and B.1.617 (Delta) SARS-CoV-2 variants, as shown in the following figures. At week 6, potent neutralization of all variants was detected, although 10.7-, 10.7-, and 5.7-fold lower against the B.1.351, P.1, and B.1.617 variants compared to the WA1/2020 strain, respectively. By week 15, the gap between neutralization titers against the WA1/2020 and other strains narrowed, mostly due to waning of titers against WA1/2020.
To determine if the spike protein is capable of reducing viral load, all NHPs were challenged with a total of 1 x 106 TCID50 of the P.1 SARS-CoV-2 isolate using simultaneous intranasal and intratracheal inoculations. Consistent with previous studies of SARS-CoV-2 in NHPs, none of the challenged macaques showed visible clinical signs of respiratory distress throughout the study. Bronchioalveolar lavages (BAL) from the lower respiratory tract and nasal (NS) and oral swabs (OS) from the upper respiratory tract were collected at days 2, 4, 7, 10, and 14 after challenge. High levels of virus were recovered from control animals two days post-challenge from the NS and BAL (black lines in below figure 3A and 3D). Virus was detectable from both sites up through day 7 post challenge and then became undetectable on day 10. All S-immunized NHPs had viral titers 1-2 Log10 lower than control animals from both the upper and lower respiratory tract throughout the study. Infectious virus from the NS was recoverable from immunized animals throughout the study period, however it was also 1-2 Log10 below those of control animals. In the following figures, vgRNA = viral genomic RNA and sgRNA = subgenomic N RNA, indicating the presence of viral RNA and viral replication, respectively.
While NHPs show no outward visible signs of illness upon infection with SARS-CoV-2, infected animals are still susceptible to acute lung injury upon microscopic evaluation of lung tissue. Histopathological evaluation of lung lobe and bronchi following staining with hematoxylin and eosin showed significant differences in the cumulative average score (based on the presence/severity of edema, intraalveolar and interstitial inflammation, perivascular lymphocytic cuffing, and increased bronchiolar-associated lymphoid tissue) for each vaccine formulation compared to controls. The cumulative average histopathology scores for all animals are shown in the following figure. Group D macaques showed mild to moderate respiratory disease, while all animals except one from Groups B and C were completely protected from lung pathology. All Group A macaques appeared to develop mild disease despite having lower viral loads.
The data generated for the prefusion S protein formulated with CoVaccine HT™ is very encouraging and shows that it generates a high level of neutralizing antibodies against the SARS-CoV-2 virus while protecting NHPs from any type of lung pathology at the higher dose. While a number of different COVID-19 vaccines are currently available, their requirements for cold chain shipping have limited their availability in a number of areas around the world. Previous work with CoVaccine HT adjuvant shows it is thermostable in combination with multiple different types of antigens, thus CiVax™ would not require cold chain distribution or storage. We look forward to additional updates from the company as it plans to approach various funding agencies with these latest results to discuss funding options to advance the CiVax™ program. Our valuation remains at $6.00 per share.
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