9 Jan 2022 Episode 219 Protection against MISC and more on therapeutic antibodies or soluble ACE-2 against omicron

Episode 219 : Protection against MISC; therapeutic antibodies or soluble ACE-2 against omicron

Dear colleagues,

In today’s episode:

• More arguments to vaccinate children: protection against MISC syndrome.
• Potential for beta Spike as a vaccine
• Several more potentially therapeutic monoclonal antibodies against omicrom
• Potential use of the soluble ACE-2 receptor as an entry blocker against omicron and other sarbecoviruses.

VACCINES

1. Protection of adolescents against Multisystem Inflammatory Syndrome in Children (MISC)

Ep 219-1: Clear protection in French adolescents: Of  33 hospitalizations Sept-Oct 2021 (Delta VOC), none had been fully vaccinated with Pfizer, 7 had received 1 dose and 26 were unvaccinated.  

Ep 219-2:  The US study is larger done between July–December 2021, a period of Delta variant.  Amongst 102 MIS-C case-patients, five (5%) were fully vaccinated with 2 doses ≥28 days before hospitalization, and 97 (95%) were unvaccinated. Vaccine efficacy was 91 %.   No fully vaccinated patients with MIS-C required respiratory or cardiovascular life support, as opposed to 39% of unvaccinated MIS-C patients. 

2. Combined Wuhan Wild Type (WT) + Beta Variant vaccine candidate: 

Ep 219-3: MVC-COV1901 is a Taiwanese protein vaccine based on the prefusion SARS-CoV-2 spike protein (S-2P) and is adjuvanted with CpG 1018 and aluminum hydroxide (similar to the US Novavax and the Chinese Clover).

A vaccination scheme with 3 doses is proposed either 3 X wild type or 2 doses WT + one Beta S-2P:

Two doses of WT S-2P + 1 dose of Beta variant  induced highest neutralizing antibody titer

• against live SARS-CoV-2 of all current variants of concern VoCs,
• and improved neutralization against Omicron variant pseudovirus

compared to three doses of wildtype S-P.

All vaccine regimens:     protected hamsters from SARS-CoV-2 Delta variant challenge

and resulted in reduced lung live virus titer and pathology.

The proposed mechanism is immune refocusing:

POTENTIALLY THERAPEUTIC ANTIBODIES

Ep 219-4: Kang Wang (China): A subset of antibodies derived from memory B cells of volunteers vaccinated with 3 doses of an inactivated SARS-CoV-2 vaccine work individually as well as synergistically to keep variants, including Omicron, at bay.

In this experiment mice were pretreated with selected monoclonal Ab and challenged with SARS-CoV-2 beta: clear protection againsty replicative virus in the lung (subgenomic RNA) 

In vitro experiments also showed good activity against omicron.

Ep 219-5: Westendorf (Eli Lilly Co) LY-CoV1404 is a human monoclonal against the receptor binding domain and potently neutralizes all variants, including omicron, in vitro.

Ep 219-6:  Fangzhu Zoa (La Jolla Ca): another example of a broad neutralizing candidate

Ep 219-7: Biao Zhou (China):

• ZCB11 is a public broadly neutralizing Ab isolated from an “elite vaccinee” (after 2 X Pfizer).
• ZCB11 administration protected against lung infection by both Delta and Omicron variants in golden Syrian hamsters.

Ep 219-8: Daniel Steward: Structural basis of Omicron neutralization by affinity-matured public antibodies

• Starting from a public class of IGHV3-53-using SARS-CoV-2 neutralizing antibodies, which  typically fails to neutralize variants carrying mutations in the RBD, including Omicron.
• Nevertheless from an individual seven months after infection several of these IGHV3 antibodies  were capable of broad and potent neutralization, including Omicron.
• The “hypermutations” needed for this transition from weak to broad neut were identified.  

Ep 219-9: Tom Yuan  (Twist Biopharma USA):  A synthetic bispecific antibody capable of neutralizing SARS-CoV-2 Delta and Omicron

This brief report highlights RBT-0813 (also known as TB493-04), a synthetic, humanized, receptor-binding domain (RBD)-targeted bispecific antibody that retains picomolar affinity to the Spike (S) trimers of all major variants of concern and neutralizes both SARS-CoV-2 Delta and Omicron in vitro.

SOLUBLE ACE-2 as a THERAPEUTIC?

Ep 219-10: Vanessa Monteil:  Clinical grade ACE2 inhibits SARS-CoV-2 Omicron 1 infections

Nice in vitro results:

Ep 219-11: Like previous SARS-CoV-2 variants, Omicron and some other sarbecoviruses showed high sensitivity against engineered ACE2, confirming the therapeutic value against diverse variants, including those that are yet to emerge.

Clearly, we are not harmless against omicron, but time is not on our side….

Best wishes,

Guido