SARS-CoV-2 vaccine--May not be possible

[Petros2015]

Depends on what you mean by 'strain'. There have been lots of mutations; which ones, if any, cause the virus to behave differently is still largely an open question.

Some take away your sense of smell; one lets you smell the color red.
Most of the others just make you really bad at math.

 

[tall73]

Some highlights from one of the traditional route trials:

Development of an inactivated vaccine candidate for SARS-CoV-2
Qiang Gao


Development of an inactivated vaccine candidate for SARS-CoV-2

To assess the immunogenicity of PiCoVacc, groups of BALB/c mice (n=10) were injected at day 0 and day 7 with various doses of PiCoVacc mixed with alum adjuvant (0, 1.5 or 3 or 6 μg per dose, 0 μg in physiological saline as the sham group). No inflammation or other adverse effects were observed. Spike-, receptor binding domain (RBD)-, and N-specific antibody responses were evaluated by enzyme-linked immunosorbent assays (ELISAs) at weeks 1-6 after initial immunization (fig. S2). SARS-CoV-2 S- and RBD-specific immunoglobulin G (Ig G) developed quickly in the serum of vaccinated mice and peaked at the titer of 819,200 (>200 μg/ml) and 409,600 (>100 μg/ml), respectively, at week 6 (Fig. 2A). RBD-specific IgG accounts for half of the S-induced antibody responses, suggesting RBD is the dominant immunogen, which closely matches the serological profile of the blood of recovered COVID-19 patients (Fig. 2, A and B) (11). Surprisingly, the amount of N-specific IgG induced is ~30-fold lower than the antibodies targeting S or RBD in immunized mice (Fig. 2A). Interestingly, previous studies have shown that the N-specific IgG is largely abundant in the serum of COVID-19 patients and serves as one of the clinical diagnostic markers (11). It’s worthy to note that PiCoVacc could elicit ~10-fold higher S-specific antibody titers in mice than those of the serum from the recovered COVID-19 patients (Fig. 2, A and B). Although this observation is currently not indicative of PiCoVacc’s ability to produce similar results in humans, it highlights the potential of PiCoVacc to induce a strong and potent immune response. Taken together, our findings - coupled with the fact that the antibodies targeting N of SARS-CoV-2 do not provide protective immunity against the infection (12) - suggest that PiCoVacc might be capable of eliciting more effective antibody responses (Fig. 2, A and B).

PiCoVacc immunization elicits neutralizing antibody response against ten representative SARS-CoV-2 isolates.

We next evaluated the immunogenicity and protective efficacy of PiCoVacc in rhesus macaques (Macaca mulatta), a non-human primate species that shows a COVID-19-like disease caused by SARS-CoV-2 infection (13).

Subsequently, we conducted a challenge study by a direct inoculation of 106 TCID50 of SARS-CoV-2 CN1 into the animal lung through the intratracheal route at day 22 (one week after the third immunization) in vaccinated and control macaques to verify the protective efficacy. Expectedly, all control (sham and placebo) macaques showed excessive copies (104-106/ml) of viral genomic RNA in the pharynx, crissum and lung by day 3-7 post-inoculation (dpi) and severe interstitial pneumonia (Fig. 3, C to F). By contrast, all vaccinated macaques were largely protected against SARS-CoV-2 infection with very mild and focal histopathological changes in a few lobes of lung, which probably were caused by a direct inoculation of 106 TCID50 of virus into the lung through intratracheal route, that needed longer time (more than one week) to recover completely (Fig. 3F).

Based on previous SARS and MERS experience all of the above was likely to be accomplished. However, the good news is that short term there was no ADE or major organ damage. Longer tests still need to be done, as that is the hurdle that the SARS and MERS vaccines struggled with.

No antibody-dependent enhancement (ADE) of infection was observed for the vaccinated macaques despite the observation that relatively low NAb titer existed within the medium dose group before infection, offering partial protection. The possibility of manifestation of ADE after antibody titers wane could not be ruled out in this study. Further studies involving observation of challenged animals at longer periods of time post vaccination are warranted to address this.

Previous reports on the development of SARS and MERS vaccine candidates raised concerns about pulmonary immunopathology, either directly caused by a type 2 helper T-cell (Th2) response or as a result of ADE (4, 14, 15). Although T-cell responses elicited by many vaccines have been demonstrated to be crucial for acute viral clearance, protection from subsequent coronavirus infections is largely mediated by humoral immunity (16, 17). The “cytokine storm” induced by excessive T-cell responses have been actually shown to accentuate the pathogenesis of COVID19 (18, 19). Therefore, T-cell responses elicited by any SARS-CoV-2 vaccine(s) would have to be well controlled in order to avoid immunopathology. In this context, we systematically evaluated safety of PiCoVacc in macaques by recording a number of clinical observations and biological indices.

In addition, histopathological evaluations of various organs, including lung, heart, spleen, liver, kidney and brain, from the 4 groups at day 29 demonstrated that PiCoVacc did not cause any notable pathology in macaques (Fig. 4C and fig. S6).