Episode 287: Epidemiology, vaccination in children and RBD vaccines
Don’t worry, this episode will be “lighter” than Ep 286…
- Slow re-emergence of the epidemic in Belgium and UK: which are the viruses, severity etc. Also data on infection- and vaccine seroprevalence from Canada
- Interesting Cuban and Chinese vaccines based on receptor-binding domain (RBD).
- Some nice papers from Hong-Kong, Canada and US on effectiveness of vaccination in children.
- As a bonus, two papers with a broader perspective….
PAR 1. Epidemiology
Ep 287-1: Sciensano report of last week (in Dutch, no Eng version): after declining figures, we see a first rise in new infections. BA.5 is dominant (94 %) and 2 “minority species BA.4 (4.3 %) and BA.2 (1.6 %). Second booster has started: already almost 50 % in 85+. (I got mine on Wednesday).
Ep 287-2: UK Health Security Agency Technical Briefing 45 of 9 Sept 2022
- While BA.5 is still dominant, with sublineages (BA.5.1; BA.5.2 and BA.5.3) and BA.4 well represented, there are two new variants in UK:
- BA.4.6 (additional mutation R346T) already 3.3 %
- BA.2.75 and sublineages still limited to 100 cases in total
- Especially BA.5.2 and BA.4.6 have growth advantage over BA.5
- Severity of BA.4 and BA.5 in UK patients (chance on hospitalization) is similar to BA.2
- Severity of BA.2.75 not evaluated in UK report, but may be higher.
Ep 287-3: in HAMSTER MODEL:
Higher lung titers (left graph) and lung lesions (right pictures) than BA.5, but lower than Delta (= B.1.617.2):
- More Inflammation in alveoli of BA.2.75 and Delta infected than BA.5 (see 4th row right)
- Also more virus (red dots) in BA.2.75 and Delta than BA.5 §see 2nd and 5th row)
Ep 287-4: Danuta Sowronski: Evolution of seroprevalence by infection and vaccination over time in Canada
Grey bars= vaccine effect; black bars = by infection
Infection-induced prevalence in younger people increases mainly between sept/Oct 21 and March 22 = Omicron BA.1/2, while in older people mainly between Mach and July/Aug = BA.5
Surveillance case reports under-estimated infections
- by 12-fold between the 6th-7th and
- 92-fold between the 7th-8th snapshots
PAR 2. RBD VACCINES
- Cuban vaccine ABDALA
Ep 287-5: Limonta-Fernandez in New Biotechnology Aug 2022: C-RBD-H6 PP = N331-K529 of the spike protein, (based on Wuhan strain) flanked by additional N- and C-terminal segments that contain polar and flexible linkers rich in Glycine and Serine, produced in Pichia pastoris yeast system, with Alum as adjuvant.
Sequence: NWSFFSNIGGSSGGSNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKGGSGGSSSSSSSSSSIEHHHHHH (residues in bold = N and C extension)
Purification and test scheme
Results of immunization of non-human primates: Induction of both higher neutralizing antibodies Convalescent serum (Fig 6 ) and strong Th1 type T cell responses in spleen and lungs (Fig 7.
Ep 287-6: Hernandez-Bernal medRxiv 10 Sept: Phase 3 with C-RBD-H6 PP = ABDALA-3
Set-up: 50 µg RBD intramuscular in 3 doses (0-14-28 days) with > 20,000 active and placebo each March-April 2021
Result: within 50 days after third dose
- 92 % effective against symptomatic disease;
- 5 critical patients: all in placebo: 4 died
- Chinese Vaccine NSVI-06-09
Ep 287-7: Yi Liang Cell Disc Feb 2022: A mutation-integrated trimeric RBD with broad protection against SARS-CoV-2
= Hybrid immunogen hetero-trimer RBD protein with sequences from prototype (Wuhan), Beta and Kappa
Immunization with hybrid immunogen compared to homo-trimer (prototype)
→ induces higher neutralization titres against prototype, delta and beta
Immunization with hybrid immunogen compared to saline
- Protects against challenge with all three SARS-CoV-3
Ep 287-8: Jin Zhang ELife Aug 2022 Mosaic trimeric RBD induces potent neutralization against omicron and other SARS-CoV-2 variants
In addition to the above “variant” trimer, the same group now developed a mosaic, where eight mutations, key to certain variants are introduced into the RBD trimer as follows
Applying this mosaic trimeric RBD as a booster to mice primed with BBIBP-CorV (inactivated vaccine) resulted in higher neutralization titers against a range of variants, including omicron subvariants. (as compared to a booster with homo-trimeric prototype RBD or BBIBP-CorV)
Ep 287-9: Nawal Al Kaabi medRxiv 6 Sept 2022: Safety and immunogenicity of a broad-spectrum mosaic vaccine as a booster dose against SARS-CoV-2 Omicron and other circulating variants
Set-up: NVSI-06-09 (20 µg mosaic trimeric RBD as in 287-7) and BBIBP-CorV are both produced by Sinopharm CNBG
They were used as a booster in subjects who received 2 or 3 doses of BBIBP at least 8 months before
Results: Safety = OK. Immunogenicity: clearly much higher neutralizing titers by the NVSI than BBIBP against prototype (Wuhan), Omicron (BA.1, BA.2, BA.4, BA.5), Beta and Delta.
- The Cuban RBD protein ABDALA is based on Wuhan strain and showed high protection during phase 3 in April 2021, when presumable alpha and beta (but not yet delta or omicron) were circulating.
- The Chinese RBD has evolved into a “mosaic” trimer protein NVSI-06-09, containing key mutations of several variants. Its efficacy has not yet been shown in people, but it is promising as a booster to the inactivated vaccine: it induces high cross-neutralizing titers, including against delta and omicron subvariants.
PAR 3. Effectiveness of vaccines in children
Ep 287-10: Dan Yu-Lin NEJM 7 Sept Effectiveness of vaccination and infection on OMICRON infection in children USA
887,193 children 5 to 11 years:
- 193,346 SARS-CoV-2 infections between March 11, 2020, and June 3, 2022;
- 309 were hospitalized,
- 7 have died
- 273,157 children at least one dose of the BNT162b2 (Pfizer) vaccine
15 hospitalizations and no known among the 273,157 vaccinated children: clearly better than in non-vaccinated
- Vaccination was less effective against the omicron variant than against delta
- Effectiveness of the vaccine was higher among previously infected children
- Waning of protection over time
The rapid decline in protection against omicron infection that was conferred by vaccination and previous infection
provides support for booster vaccination.
Ep 287-11: Rosa Duque medRxiv 8 Sept 2022: Effectiveness of BNT162b2 and CoronaVac against pediatric COVID-
19-associated hospitalization and moderate-to-severe disease in Hong-Kong.
Set-up: VE for children aged 3-11 years vs adolescents aged 12-18 years at the population level during the Omicron BA.2 wave (Jan – April 2022), using an “ecological design” leveraging the HK vaccination coverage statistics and public hospital records.
- VE higher for Pfizer than CoronaVac (= inactivated): min 2 doses of CoV needed
- VE in children and adolescents similarly high.
Estimate of averted hospitalization: 68 for children and 999 for adolescents.
PAR 4: BONUS
Par 287-12: Carina Sagau Imunity Oct 2022 The pre-exposure SARS-CoV-2-specific T cell repertoire determines the quality of the immune response to vaccination
This paper shows that the quality of pre-existing T cells in the “naïve” repertoire is predictive of the strength of the response to the vaccine: naïve T cells have a higher expansion potential, with higher avidity (= functional affinity for Spike) and more IL-21 production, which is needed for high quality antibody production.
Immune ageing is associated with expansion of a “memory” phenotype, which lacks those characteristics and therefore results in poor antibody quality, and rapidly waning immunity after vaccination.
Ep 287-13: Final Report of the Lancet Commission on COVID-19.
For most of us, it doesn’t contain a lot of surprises, but it is a good reference document.
That’s it for this week.
12 Sept 2022 Episode 286 Update and real world experience with Remdesivir, Paxlovid and Molnupiravir
> More info
3 Sept 2022 Episode 285: Further data and discussion on protection by infection and bivalent vaccines in in the omicron era.
> More info
9 August Episode 279: BA.2.75, novel monoclonal Ab, polymerase and anti-inflammatory treatment options
> More info