30 Dec 2021 Episode 212 More on omicron: effect of booster, T cells and epidemiology

Episode 212 : Omicron : booster effect, T cell immunity and epidemiology  

Booster effect

Ep 212-1 : Very interesting study from South-Africa comparing a two dose Janssen Ad26.CoV2 (second dose 6-9 months after the first, just prior to omicron emergence) with unvaccinated individuals. 

Vaccine efficacy against hospital admission was 63 % 0-13 days after boost and then increased to 84-85 % up to 2 months.  Clearly, it is still a mixed delta-omicron viral population (no systematic genotyping), but the efficacy was similar in Gauteng (where omicron was already dominant) as in other provinces, where delta was still present or dominant.

Table 1 gives also a first idea on how “pathogenic” omicron may be: in unvaccinated 4 % of positively tested subjects was hospitalized.  There was a clear age gradient in hospitalizations (vacc and unvacc mixed): 30-39: 2.4%; 40-49: 3 %; 50-60: 5.4 %; 60-69: 11 %; 70-79: 23 % and 80+: 37%.

Ep 212-2: Perez-Then Immunogenicity of mRNA Pfizer 4 weeks after 2 doses of inactivated CoronaVac.

• 2 doses CoronaVac induced NO neutralizing Ab against omicron, weak responses to Wuhan and delta (as compared to 2 doses of Pfizer)
• Booster with Pfizer induced neut Ab to Wuhan > Delta > omicron. Levels almost equivalent to 2 doses of Pfizer.
• (No enhancing effect of previous infection on level of neut Ab against omicron).

T cell immunity

Ep 212-3:  Roanne Keaton et al show that CD4 and CD8 T cell responses to omicron Spike, Membrane and Nucleocapside peptide pools are similar as compared to ancestral, beta and delta.   This is shown for Pfizer or Janssen vaccinated or convalescent subjects (Fig 1) as well as in hospitalized subjects in the various epidemic waves (Fig 2).  The “quality” of the response is also controlled for by looking at “polyfunctionality” (simultaneous production of various cytokines).

Overall, these results demonstrate that vaccination and infection induce a robust CD4 and CD8 T cell response that largely cross-reacts with Omicron, consistent with … limited T cell escape

by Beta, Delta and other variants,

which is in sharp contrast with clear-cut and progressive escape in neutralizing antibody response.

However, this cross-sectional study give no direct evidence of protective immunity by T cells, as responses are apparently independent of vaccination or disease: they show “sensitization” to the viral antigens.

Ep 212-4: Very similar results presented by GeurtsvanKessel on HCW vaccinated with either AZ, Janssen, Pfizer or Moderna:

1. Antibody responses:

• High binding antibody levels against WT SARS-CoV-2 spike (S) were detected 28 days after vaccination with both mRNA vaccines (mRNA-1273 or BNT162b2), which significantly decreased after 6 months. In contrast, antibody levels were lower after Ad26.COV2.S vaccination but did not wane.
• Neutralization assays with live virus showed consistent cross-neutralization of the Beta and Delta variants in study participants, but Omicron-specific responses were significantly lower or absent.
• Booster partially restored neutralization of the Omicron variant, but responses were still up to-17-fold decreased compared to D614G.

2. T cell responses:

• CD4+ T-cell responses were detected up to 6 months after all vaccination regimens; S-specific T-cell responses were highest after mRNA-1273 vaccination. No significant differences were detected between D614G- and variant specific T-cell responses, including Omicron, indicating minimal escape at the T-cell level.

Epidemiology

Ep 212-5: Garret reports on a very high rate of asymptomatic omicron carriage in people living with HIV (31%) and in HCW (16%) in December 2021 in South-Africa, tested in the context of receiving a vaccine. The rate was the same in SARS-CoV-2 sero-positive and -negative subjects.  These figures are almost 10 times higher than in similar studies during the Delta wave. Clearly these data testify of the rapid spread of this variant, irrespective of previous infection.

Ep 212-6: Evidence of higher transmissibility of omicron compared to delta in Danish households:

• Secondary attack rate = 31 % for omicron and 21 % for delta.
• Omicron infected unvaccinated 1.17 x more than delta, but 2.6 X more in 2 dose vaccinated and 3.6 X more in 3 dose vaccinated!  Hence very clear immune escape   (See Table 1)

The good news: full vaccination protects against delta, but not omicron, while booster protects clearly against both delta and omicron (Table 2).

Ep 212-7: Waldstrom: Increased severity of Alpha and Delta variant, as compared to D614G in Swedish unvaccinated SARS-CoV-2 infected subjects 2020-2021:

After adjustment for age, sex, and socio-economic factors, and with November 2020 (non-

VOC period) as reference,

• Odds ratios (OR) for hospitalization were 1.6-1.7 in March-May 2021 (Alpha VOC dominance) and 2.4-3.0 in June-September 2021 (Delta VOC dominance)
• ORs for severe illness were 1.8-2.1 in March-May 2021 and 3.1-4.7 in June- Sept 2021.

This study shows that unvaccinated adults without risk factors, have had a gradually increased risk for hospital admission and severe illness when infected with the Alpha and Delta VOCs, respectively.

Ep 212-8: A new SARS-CoV-2 variant with spike substitutions N501Y and E484K in South-East France: apparently imported from Cameroon and found in 12 subjects. It contains 45 mutations and 37 deletions, spread over non-structural and structural genes, but with 14 mutations and 12 deletions in Spike.  Designated B.1.640.2  

Some conclusions:

• Clear evidence that booster vaccination provides some additional protection against infection and hospitalization with omicron.
• T cell responses against several VOC (including omicron) much better preserved than antibody responses, which become less efficient over the consecutive VOC. 
• Remember that because of their mechanism of action (recognition of cell-associated virus only) T cells are not likely to protect against first infection, but they can limit an established infection and hence protect against the pathology. 
• Why is there apparently no immune escape from T cells (while it is very evident for B cells)?
  • Either no immune pressure on SARS-CoV-2 by T cells (implying that T cells do not play a major role in defense)?
  • Or T cell epitopes are more “conserved” i.e. the virus cannot change them without serious loss in fitness?

Food for thought and to accumulate more longitudinal data on the relation between T cell responses and disease evolution in patients….

Best wishes,

Guido