Thread by @HelenBranswell

1. #ACIP is meeting today to decide on whether to recommend use of the the bivalent Covid vaccines. It was first posted as a 2-day meeting but they now expect it to be a 1-day meeting.
I will be live tweeting.
The meeting is being streamed here: video.ibm.com/channel/VWBXKB…

2. #ACIP chair Grace Lee noted that the committee didn't meet in August. She didn't say, but I think that might have been the first month since the fall of 2020 that ACIP hasn't met at least once in a month. These folks have worked so hard throughout the pandemic.

3. Lee is calling the roll call using her random approach (rather than going by alphabetic order). Hate this approach. Makes it hard to figure out if everyone is there.
Sounds like at least 1 member isn't currently on the call, Dr. Pablo Sanchez.

4. Dr. Sanchez is now in the #ACIP meeting.
I'm not clear if Drs. Kevin Ault or Sarah Long are on the call. Grace Lee just said ACIP has a quorum, which suggests to me that some of the 15 ACIP members are not present.

5. As #ACIP embarks on the discussion of whether to recommend use of the updated Pfizer & Moderna boosters, it bears noting that to date, more than 12.6B doses of Covid vaccines have been given around the globe since late 2020.
This is an extraordinary feat.
(source: Bloomberg)

6. @CDCgov's Heather Scobie is summing up for #ACIP how the pandemic has played out so far in the U.S., as well as vaccine uptake data & the apparent impact of vaccine, such as in this slide showing the rate at which unvaxed people were hospitalized compared to vaxed people.

7. As well, adults who had a primary series + 2 boosters had a 14 times lower risk of death from Covid than unvaxed people. And people who had a 2nd booster had a 3x lower risk of death than people who had only 1 booster. #ACIP

8. I'm told all #ACIP members are present except @kevinault. Unless he joins later, there should be 14 voting members when the votes are taken later this afternoon.

9. #ACIP looks like it could be off schedule already. There are meant to be 4 presentations from 10:15 to noon. Still taking questions on the first presentation. Three more to go, on immunology of the SARS-2 variants, updates on vaccine efficacy & vaccine safety.

10. @CDCgov's Natalie Thornburg is presenting on antigenic cartography -- how different strains are from one another in term of the immune system's ability to cross protect against them.

11. This is a complex presentation. I'm not going to try to sum it up other than to say that by @CDCgov's estimate, BA.4/BA.5 may be more antigenically different from the Wuhan strain than any other of the Omicron sub-variants. The updated boosters the US will use contain BA.4/5.

12. But Thornburg said that different results could be reached by different groups if they used different assays.
Interestingly, @WHO's vaccine experts, The SAGE, recommended using BA.1 in the bivalent boosters because they said it was the most genetically distinct subvariant.

13. @CDCgov's Ruth Link-Gelles is presenting on the vaccine efficacy of Covid vaccines. The waning of these vaccines is really profound and pretty quick.
This is against any symptomatic infection. Protection against severe disease is more durable.

14. Link-Gelles says the efficacy appears to be waning more slowly from dose 4 than previous doses, but the confidence intervals on this are wide so it isn't certain.

15. So #ACIP is speeding through the other presentations in this morning session. The final of 4 @CDCgov presentation is starting now. Tom Shimabukuro is talking about Covid vaccine safety. He's presented on this so often he could probably do it in his sleep.

16. But now Shimabukuro is now presenting on the safety data in children 6 months to 4 years — the first time I've heard data presented on this group since the vaccines were authorized for them. No reports of myocarditis in this age group.

17. Side-effect reporting in kids 6 to 23 months & 2 to 4 yrs shows slightly more reactogenicity in kids who got the Moderna vaccine after the 2nd dose.
Shimabukuro says there've been no unexpected safety findings in young children to this point.

17. Shimabukuro is also presenting data on side effects reported after the first booster dose in children aged 5 to 12. #ACIP

18. And side effects reported after the first booster dose in kids 12 and up. #ACIP

19. This is a glimpse at reported reactions & reactogenicity of both the Pfizer & Moderna vaccines in people who've had 4 doses. Reactions peak after dose 2 & decline with subsequent doses.
This was not my experience.
#ACIP

20. Shimabukuro sums up what the safety data show to date. Notations on the slide are mine.
#ACIP

21. Shimabukuro says there are no signals of problematic reactions to Covid vaccination in pregnant people.

22. #ACIP takes a 10 minute lunch break.

23. The public comment section of the #ACIP meeting is underway. The evaluation of the updated Covid boosters is scheduled to resume at 1 pm Eastern.

24. #ACIP resumes early. Moderna's Jacqueline Miller is now presenting data on her company's bivalent vaccine, which contains 50 micrograms of antigen, half of which targets the Wuhan strain & half an Omicron strain, BA.4/BA.5.
Can someone explain to me which it is? 4? 5?

25. Moderna's safety & immunogenicity data on bivalent Covid vaccines are based on earlier work on bivalents that targeted Wuhan & Beta, or Wuhan & BA.1. A study looking at Wuhan & BA4./BA.5 concluded enrollment yesterday, Miller said.

26. Thanks for the answers, folks. The spikes of BA.4 & BA.5 are identical. (Which I should know but I've been immersed in monkeypox and polio of late.)
nature.com/articles/s4159…

27. Moderna's Miller said (in the study of the bivalent containing BA.1) they were looking to show that the protection of the bivalent vaccine was superior to the monovalent vaccine in generating neutralizing antibodies to the Omicron strain. This was met, she said. #ACIP

28. Moderna's Miller said they also wanted to show that the bivalent vaccine induced neutralizing antibodies against the Wuhan strain that were at levels non-inferior to previous vaccinations. Also met, she said. #ACIP

29. Moderna's Miller said their bivalent vaccine targeting BA.1 (not the vaccine under consideration today) induced higher levels of binding antibodies to other variants of concerns.
Reading antibody titers isn't my specialty. But these improvements seem modest, no? #ACIP

30. Moderna's Miller says the company is studying boosters in kids 6 to 17 yo and expect to file to @US_FDA by the end of Sept. The study on children 6 months to 5 years is expected to be concluded by the end of the year. #ACIP

31. To my earlier tweet (#29), @SarahKarlin says:

32. Pablo Sanchez, who is often a voice of caution on #ACIP, asked if moving on these boosters isn't a bit premature, given that the human trial is just being done now.

33. Pfizer is now presenting its data. Kena Swanson is presenting. She notes the company has done a lot of work studying vaccines targeting earlier SARS-2 variants of concern. But as with Moderna, Pfizer's clinical trial of the booster authorized yesterday is still underway.

34. Swanson shows that with a bivalent vax with Wuhan + an Omicron strain (bars at the right) the breadth of the response to a variety of SARS-2 strains was greater than the original vax or an Omicron alone vaccine. Caveat: work done in naive mice. Most humans aren't Covid naive.

35. Swanson says similar breadth of response is seen when pre-vaccinated mice were given an Omicron-containing booster. #ACIP (notation on the slide is mine.)

36. #ACIP chair Grace Lee is concerned about the multiple products and the multiple colored caps, which distinguish adult formulations from the various pediatric formulations. It must be confusing.

37. @CDCgov's Sara Oliver is presenting now. She told #ACIP that going forward, attention will shift away from whether you've had a 3rd or 4th or 5th (if you are immunocompromised) shot, to whether you've had a primary series & a bivalent booster. (notation mine)

38. Oliver is currently going through what can be deduced about bivalent booster efficacy and accumulated safety data on Covid vaccines. This is repetitive of information presented earlier today.

39. Oliver notes that there is still no evidence that getting additional doses of Covid vaccine will trigger immune tolerance -- ie diminishing responses. #ACIP

40. Oliver also suggested that imprinting (a.k.a. original antigenic sin) doesn't appear to be a problem that would impede response to the bivalent vaccine.
There are scientists who would probably argue differently.
#ACIP

41. Oliver notes that the risk of reinfection fundamentally changed in the era of Omicron. #ACIP

42: Unknowns at the moment about the updated Covid boosters, per Sara Oliver's presentation. #ACIP

43. A @CDCgov survey, conducted in August, suggests 72% of people will definitely or probably get an updated booster. That would be a higher rate than for 3rd or 4th shots. #ACIP

44. Who will be eligible for a bivalent booster? People who are 12 and older who have had a primary series and have not had a shot in the past 2 months. People who have received a shot within the past 2 months will need to wait until they are outside that window. #ACIP

45. More labeling confusion: People giving Covid vaccines are really going to need to be on their toes when reaching into the fridge. Pfizer & Moderna vials have similar caps, but different injection volume.
Moderna's bivalent has a cap similar to the vax for kids 6-11. #ACIP

46. Estimates of benefits that may come from the bivalent boosters: modeling estimates of deaths, hospitalizations, infections & costs averted, based on uptake similar to seasonal flu shots (left) & if 80% of those eligible took the shot (right). #ACIP

47. The current presentation, which is about a simplification of the # of boosters people are entitled to, is going to confuse people before it simplifies things. Going forward, people are eligible for 1 bivalent booster after a primary series. #ACIP

48. But this doesn't mean that people who have had multiple boosters already — 2 if you're over 50 yo, 3 if you are immunocompromised — can't get this new booster. They can. This simplified approach is in effect going forward. #ACIP

48. @CDCgov is making a push for better use of Evusheld, the antibody prophylaxis which has been underused among immunocompromised people. (Not their fault!)

49. If you've recently had Covid, here's what you need to know about how to time receipt of a bivalent booster.
Covid vaccines can be given at the same time as other vaccines, with the exception of #monkeypox vaccine. #ACIP

50. @CDCgov is urging vaccine providers to give both Covid boosters & flu shots at the same time.
I understand that it makes things easier and may improve uptake of flu vaccine. But Sept is early to get a flu shot. CDC normally says get it by the end of Oct. #ACIP

51. More cap confusion:
People administering these vaccines are going to need to be so on guard. @CDCgov knows this and is planning information sessions to try to help providers avoid making errors. #ACIP

52. Seems like a situation providers will need to be on alert about is the similarities between Moderna's bivalent booster and the company's vaccine for kids 6-11 yo. #ACIP

53. #ACIP member Sybil Cineas asks what vaccine deliverers should do if they mix up the Pfizer primary series vial & the bivalent vial. Ie, if someone gets the bivalent vaccine as part of their primary series by mistake. @CDCgov said: Don't repeat the dose.

54. #ACIP is now starting the discussion of the voting questions, which is/are:
It's presented here as 1 Q, but I suspect there are going to be separate votes on each of the vaccines.

55. Lots of concerns voiced about the lack of human data for the bivalent vaccines that #ACIP has been presented — human data presented have been for a bivalent including a different Omicron strain. But some members acknowledge the impact of waiting 3 months to get BA.4/5 data.

56. @CDCgov's Melinda Wharton, who is #ACIP's executive secretary (or somesuch), is reminding the committee that this is the way flu vaccine is updated yearly.
@US_FDA's Doran Fink acknowledges this is a "leap" that hasn't been made before for Covid vaxes.

57. But @US_FDA's Fink says that a lot is now known about Covid vaccines & FDA felt comfortable authorizing the updated vaccines. #ACIP

58. Hearing a fair amount of fretting among #ACIP members. Sarah Long asked if there was discussion about limiting the new boosters to people 50+. Matt Daley said the ACIP's Covid Work Group did discuss it. Keipp Talbot said it was thought that would make things too complicated.

59. At the start of this meeting I thought these votes would be unanimous. Not sure now. A number of #ACIP members are very uncomfortable with the lack of human data. And quite a few are really worried about the prospect for making administration errors because of vial labeling.

60. #ACIP chair Grace Lee says that although the @US_FDA EUA allows these vaccines to be given 2 months after a previous Covid shot, she will recommend to patients that they wait 3 months. Could get better results from the longer interval & lower the myocarditis risk.

61. #ACIP votes 13 - 1 to recommend use of the Pfizer-BioNTech bivalent Covid vaccine for people 12 and older.

62. #ACIP votes 13 - 1 to recommend use of the Moderna bivalent Covid booster for people 18 and older.
The only person who voted against was Pablo Sánchez.

63. #ACIP is done!