Dr. Paul Offit, MD, FDA advisor, said the i) bivalent boosters failed & came up with a bogus reason! ii) The science I have been reporting said it failed too; altogether, the bivalent booster BA 4/5

is a complete abject FAILURE!

i)Offit:

SOURCE:

https://www.nejm.org/doi/full/10.1056/NEJMp2215780?utm_source=substack&utm_medium=email

‘On October 24, 2022, David Ho and colleagues released the results of a study examining levels of neutralizing antibodies against BA.4 and BA.5 after receipt of a monovalent or bivalent booster dose. They found “no significant difference in neutralization of any SARS-CoV-2 variant,” including BA.4 and BA.5, between the two groups.³ One day later, Dan Barouch and colleagues released the results of a similar study, finding that “BA.5 [neutralizing-antibody] titers were comparable following monovalent and bivalent mRNA boosters.” Barouch and colleagues also noted no appreciable differences in CD4+ or CD8+ T-cell responses between participants in the monovalent-booster group and those in the bivalent-booster group.⁴ Neither research group found the bivalent boosters to elicit superior immune responses. The results are now published in the Journal.’

ii)my review of the failure:

62) Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants, Wang, 2022“BQ.1, BQ.1.1, XBB, and XBB.1 are the most resistant SARS-CoV-2 variants to date;
Serum neutralization was markedly reduced, including with the bivalent booster;
All clinical monoclonal antibodies were rendered inactive against these variants;
The ACE2 affinity of these variants were similar to their parental strains;
 
The BQ and XBB subvariants of SARS-CoV-2 Omicron are now rapidly expanding, possibly due to altered antibody evasion properties deriving from their additional spike mutations. Here, we report that neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 by sera from vaccinees and infected persons was markedly impaired, including sera from individuals boosted with a WA1/BA.5 bivalent mRNA vaccine. Titers against BQ and XBB subvariants were lower by 13-81-fold and 66-155-fold, respectively, far beyond what had been observed to date. Monoclonal antibodies capable of neutralizing the original Omicron variant were largely inactive against these new subvariants, and the responsible individual spike mutations were identified. These subvariants were found to have similar ACE2-binding affinities as their predecessors.

Together, our findings indicate that BQ and XBB subvariants present serious threats to current COVID-19 vaccines, render inactive all authorized antibodies, and may have gained dominance in the population because of their advantage in evading antibodies.”

63) Low neutralization of SARS-CoV-2 Omicron BA.2.75.2, BQ.1.1, and XBB.1 by parental mRNA vaccine or a BA.5-bivalent booster, Kurhade, 2022“The newly emerged SARS-CoV-2 Omicron sublineages, including the BA.2-derived BA.2.75.2 and the BA.5-derived BQ.1.1 and XBB.1, have accumulated additional spike mutations that may affect vaccine effectiveness. Here we report neutralizing activities of three human serum panels collected from individuals 23–94 days after dose 4 of a parental mRNA vaccine, 14–32 days after a BA.5-bivalent-booster from individuals with 2–4 previous doses of parental mRNA vaccine, or 15–32 days after a BA.5-bivalent-booster from individuals with previous SARS-CoV-2 infection and 2–4 doses of parental mRNA vaccine. The results showed that a BA.5-bivalent-booster elicited a high neutralizing titer against BA.4/5 measured at 14- to 32-day post-boost; however, the BA.5-bivalent-booster did not produce robust neutralization against the newly emerged BA.2.75.2, BQ.1.1, or XBB.1. Previous infection significantly enhanced the magnitude and breadth of BA.5-bivalent-booster-elicited neutralization. Our data support a vaccine update strategy that future boosters should match newly emerged circulating SARS-CoV-2 variants.”

64) Effectiveness of the Coronavirus Disease 2019 (COVID-19) Bivalent Vaccine, Shrestha, 2022 “A retrospective cohort study conducted at the Cleveland Clinic Health System (CCHS) in the United States.
Researchers included employees on the very day that the bivalent COVID-19 vaccine was first available. 
‘Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression.’
Findings focused on 51,011 employees of which 20,689 (41%) had a prior documented COVID-19 infection (episode), and whereby 42,064 (83%) received at least two doses of the vaccine. 
‘The majority of infections in Ohio were caused by the BA.4 or BA.5 lineages of the Omicron variant during the first 10 weeks of the study, based on SARS-CoV-2 variant monitoring data available from the Ohio Department of Health. By December, the BQ.1, BQ.1.1, and BF.7 lineages accounted for a substantial proportion of the infections.’
‘By the end of the study, 10804 (21%) were bivalent vaccine boosted. The bivalent vaccine was the Pfizer vaccine in 9595 (89%) and the Moderna vaccine in the remaining 1178. Altogether, 2452 employees (5%) acquired COVID-19 during the 13 weeks of the study.’
‘The calculated overall vaccine effectiveness from the model was 30% (95% C.I., 20% – 39%)…when the Omicron BA.4/BA.5 lineages were the predominant circulating strains.’
‘The multivariable analyses also found that, the more recent the last prior COVID-19 episode was the lower the risk of COVID-19, and that the greater the number of vaccine doses previously received the higher the risk of COVID-19.”

65) Effectiveness of second booster compared to first booster and protection conferred by previous SARS CoV-2 infection against symptomatic Omicron BA.2 and BA.4/5 in France, Tamandjou, 2023“We included symptomatic ≥60 years old individuals tested for SARSCoV-2 in March 21-October 30, 2022. Compared to a 181-210 days old first booster, a second booster restored protection with an effectiveness of 39% [95%CI: 38% – 41%], 7-30 days postvaccination This gain in protection was lower than the one observed with the first booster, at equal time points since vaccination.”

66) Extended SARS-CoV-2 RBD booster vaccination induces humoral and cellular immune tolerance in mice, Gao, 2023i) Our findings demonstrate potential risks with the continuous use of SARS-CoV-2 vaccine boosters, providing immediate implications for the global COVID-19 vaccination enhancement strategies.

ii) Whether such re-establishment of vaccine-induced immune response could be repeated by continued application of boosters is being questioned, yet largely unknown at present. Here, we compared the effects of repeated RBD vaccine boosters with a conventional immunization course to those with an extended vaccination strategy, in a Balb/c mice model.

iii) We found that the protective effects from the humoral immunity and cellular immunity established by the conventional immunization were both profoundly impaired during the extended vaccination course. Specifically, extended vaccination not only fully impaired the amount and the neutralizing efficacy of serum RBD-specific antibodies, but also shortened the long-term humoral memory.

iv) This is associated with immune tolerance in germinal center response, along with decreased numbers of spleen germinal center B and Tfh cells. Moreover, we demonstrated that extended immunization reduced the functional responses of CD4+ and CD8+T cells, restrained the population of memory T cells, and up-regulated the expression of PD-1 and LAG-3 in Te sub-type cells.

v) An increased percentile of Treg cells was also observed, accompanied by significant elevation of IL-10 production. Together, we provided crucial evidence that repetitive administration of RBD booster vaccines may negatively impact the immune response established by a conventional vaccination course and promote adaptive immune tolerance.’

vi) Continued vaccination promoted the formation of a prominent adaptive immune tolerance and profoundly impaired the established immune response with the conventional course, evidenced by significant reductions in antigen specific antibody and T cell response, a loss of immune memory and form of immunosuppression micro-environment.

67) Effect of prior infection, vaccination, and hybrid immunity against symptomatic BA.1 and BA.2 Omicron infections and severe COVID-19 in Qatar, Altarawneh, March 2022“Qatar researchers investigated SARS-CoV-2 Omicron symptomatic BA.1 infection, symptomatic BA.2 infection, BA.1 hospitalization and death, and BA.2 hospitalization and death, between December 23, 2021 and February 21, 2022. The researchers conducted 6 national, matched, test-negative case-control studies were conducted to examine effectiveness of BNT162b2 (Pfizer-BioNTech) vaccine, mRNA-1273 (Moderna) vaccine, natural immunity due to prior infection with pre-Omicron variants, and hybrid immunity from prior infection and vaccination. They found that “Effectiveness of only prior infection against symptomatic BA.2 infection was 46.1% (95% CI: 39.5-51.9%). Effectiveness of only two-dose BNT162b2 vaccination was negligible at -1.1% (95% CI: -7.1-4.6), but nearly all individuals had received their second dose several months earlier. Effectiveness of only three-dose BNT162b2 vaccination was 52.2% (95% CI: 48.1-55.9%). Effectiveness of hybrid immunity of prior infection and two-dose BNT162b2 vaccination was 55.1% (95% CI: 50.9-58.9%).” The key finding was “There are no discernable differences in the effects of prior infection, vaccination, and hybrid immunity against BA.1 versus BA.2.” 

68) Effectiveness of a fourth dose of mRNA COVID-19 vaccine against all-cause mortality in long-term care facility residents and in the oldest old: A nationwide, retrospective cohort study in Sweden, Nordström, 2022“From 7 days after baseline and onwards, there were 1119 deaths in the LTCF cohort during a median follow-up of 77 days and a maximum follow-up of 126 days. During days 7 to 60, the VE of the fourth dose was 39% (95% CI, 29-48), which declined to 27% (95% CI, -2-48) during days 61 to 126. In the cohort of all individuals aged ≥80 years, there were 5753 deaths during a median follow-up of 73 days and a maximum follow-up of 143 days. During days 7 to 60, the VE of the fourth dose was 71% (95% CI, 69-72), which declined to 54% (95% CI, 48-60) during days 61 to 143.”

69) Risk of infection, hospitalisation, and death up to 9 months after a second dose of COVID-19 vaccine: a retrospective, total population cohort study in Sweden, Nordström, 2022“For the outcome SARS-CoV-2 infection of any severity, the vaccine effectiveness of BNT162b2 waned progressively over time, from 92% (95% CI 92 to 93; p<0·001) at 15-30 days, to 47% (39 to 55; p<0·001) at 121-180 days, and to 23% (-2 to 41; p=0·07) from day 211 onwards. Waning was slightly slower for mRNA-1273, with a vaccine effectiveness of 96% (94 to 97; p<0·001) at 15-30 days and 59% (18 to 79; p=0·012) from day 181 onwards. Waning was also slightly slower for heterologous ChAdOx1 nCoV-19 plus an mRNA vaccine, for which vaccine effectiveness was 89% (79 to 94; p<0·001) at 15-30 days and 66% (41 to 80; p<0·001) from day 121 onwards. By contrast, vaccine effectiveness for homologous ChAdOx1 nCoV-19 vaccine was 68% (52 to 79; p<0·001) at 15-30 days, with no detectable effectiveness from day 121 onwards (-19% [-98 to 28]; p=0·49). For the outcome of severe COVID-19, vaccine effectiveness waned from 89% (82 to 93; p<0·001) at 15-30 days to 64% (44 to 77; p<0·001) from day 121 onwards. Overall, there was some evidence for lower vaccine effectiveness in men than in women and in older individuals than in younger individuals.”

70) Neutralization against BA.2.75.2, BQ.1.1, and XBB from mRNA Bivalent Booster, Davis-Gardner, 2023“Used the FRNT in a VeroE6/TMPRSS2 cell line¹ to compare the neutralizing activity in serum samples obtained from participants in three cohorts: the first cohort comprised 12 participants 7 to 28 days after one monovalent booster; the second, 11 participants 6 to 57 days after a second monovalent booster; and the third, 12 participants 16 to 42 days after a bivalent booster.
 
In all three cohorts, neutralization activity was lower against all omicron subvariants than against the WA1/2020 strain; neutralizing activity was lowest against the XBB subvariant (Figure 1 and Fig. S2). In the cohort that received one monovalent booster, the FRNT₅₀ GMTs were 857 against WA1/2020, 60 against BA.1, 50 against BA.5, 23 against BA.2.75.2, 19 against BQ.1.1, and below the limit of detection against XBB. In the cohort that received two monovalent boosters, the FRNT₅₀ GMTs were 2352 against WA1/2020, 408 against BA.1, 250 against BA.5, 98 against BA.2.75.2, 73 against BQ.1.1, and 37 against XBB. The results in both of these cohorts correspond with neutralization titers against BA.1 and BA.5 that were 5 to 9 times as low as that against WA1/2020 and neutralization titers against BA.2.75.2, BQ.1.1, and XBB that were 23 to 63 times as low as that against WA1/2020.”

71) Neutralization Escape by SARS-CoV-2 Omicron Subvariants BA.2.12.1, BA.4, and BA.5, Hachmann, 2022“Six months after the initial two BNT162b2 immunizations, the median neutralizing antibody pseudovirus titer was 124 against WA1/2020 but less than 20 against all the tested omicron subvariants. Two weeks after administration of the booster dose, the median neutralizing antibody titer increased substantially, to 5783 against the WA1/2020 isolate, 900 against the BA.1 subvariant, 829 against the BA.2 subvariant, 410 against the BA.2.12.1 subvariant, and 275 against the BA.4 or BA.5 subvariant.
 
Among the participants with a history of Covid-19, the median neutralizing antibody titer was 11,050 against the WA1/2020 isolate, 1740 against the BA.1 subvariant, 1910 against the BA.2 subvariant, 1150 against the BA.2.12.1 subvariant, and 590 against the BA.4 or BA.5 subvariant.”