Views my own, but you can borrow them if you feel so inclined. Anti-disease. Big Nerd Energy. “A homework person.” Fun at parties. Antibody hoarder. he/him
New post in which I discuss a recent Perspective on post-authorization vaccine safety studies and how it's being misrepresented (and add in a few thoughts on what I think the perspective misses):
open.substack.com/pu...
At the previous ACIP meeting, preliminary data investigating this risk was shared showing no obvious imbalance in the risks of preterm births from VSD, based on about 10,000 pregnancies documented in the study interval:
jamanetwork.com/jour...
This new study adds to this data using a cohort of 2973 patients who delivered during the 2023 to 2024 recommended vaccination period, 34.5% had evidence of prenatal RSVpreF vaccination. In this study, no increased risk of preterm delivery or other select outcomes is noted.
In their studies, there was a small imbalance in preterm births that varied a lot across between trial sites, with the overwhelming majority of the imbalance in risks being driven by cases from South Africa.
www.cdc.gov/vaccines...
Pardon me as I scream into a pillow about the fact that Johnson & Johnson slashed Janssen's vaccine R&D and abandoned their adult RSV vaccine even though that protected older adults from severe RSV for *3 seasons* with a single dose:
www.sciencedirect.co...
Safety monitoring of Nirsevimab is monitored mainly through FAERS and Medwatch because it is technically a drug rather than a vaccine. Basically, allergic reactions have been seen which is not surprising, and some breakthrough infections have been seen. Safety is reassuring.
Also worth noting that some of the reactions to nirsevimab are probably startle/vasovagal reactions. Nirsevimab's effectiveness is phenomenal.
We don't yet have data on the effectiveness of maternal RSV vaccine though.
We do not yet know when/whether maternal RSV vaccines need boosters (I would guess probably with every pregnancy but no data right now to inform this). Second dose raises antibody titers above baseline but not to levels seen post-dose 1 in nonpregnant adults.
Okay now my favorite part: the data on the effectiveness of nirsevimab (a long-lasting RSV monoclonal antibody) in babies: www.cdc.gov/vaccines...
It is FANTASTIC news.
Like with vaccines, you can measure effectiveness by a test-negative design. To help us do this, first we have the VISION network. Using this design and study cohort, Nirsevimab had an effectiveness of 98% against RSV hospitalization and 77% against RSV-associated emergency visit
Next we have data from NVSN. The antibody became available at sites in the middle of RSV season. Similar to VISION, Nirsevimab was found to be 91% effective against RSV hospitalization and 89% effective at preventing medically-attended RSV in babies.
These results are similar to those reported in clinical trials and seen abroad. All described studies have some limitations such as the potential for residual confounding. Nonetheless, data on nirsevimab are incredibly positive.
EVERY baby should have access to this antibody.
that the incidence was really complex and varied a lot by trial site, and the effect of vaccination (if real) was delayed e.g., 4+ weeks to preterm birth. Given this, it was decided to restrict the use of the vaccine to 32-36 weeks instead of 28 weeks as in the trial.
Because of this, the first priority of safety monitoring was to confirm no increased risk of preterm birth from the Pfizer maternal RSV vaccine. Based on data from VSD, VSAFE, and VAERS, as of now, there does not appear to be a heightened risk of preterm birth (yay!).
Here's a summary of the VAERS data. Basically- there isn't any increased risk apparent here. Notably, of the preterm births here, nearly all were late preterm which generally has excellent outcomes. Most reports were filled out by pregnant individuals themselves.
V-SAFE was also used to monitor the vaccines. This is a form of active surveillance- the system regularly checks in with you to see what your experience is after vaccination. This addresses some of the weaknesses of VAERS (see previous slides).
VSD is perhaps the most powerful vaccine safety monitoring system the US has. This uses medical records to compare the risks of vaccinees to non-vaccinees. In VSD, about 10,000 vaccines were given in pregnancy, with about 4.1% associated with preterm birth. This is no greater...
Now come the presentations on RSV vaccinations (and nirsevimab) for maternal and pediatric patients:
www.cdc.gov/vaccines...
Here are the current recommendations. CRITICALLY: GSK's vaccine cannot be used in pregnant individual. Neither vaccine can be given to infants.
Next presentation: www.cdc.gov/vaccines...
1/5 people did take the RSV vaccines in pregnancy and about half of eligible infants did get protection from RSV- but that's still a lot less than we want (RSV is the leading cause of hospitalization in babies). Note racial disparities.
In terms of implementation... there were hiccups. The recommendation for nirsevimab ended up being a lot broader than Sanofi, the manufacturer, was prepared to accommodate. Hence accessing nirsevimab was really tough. There were also issues with cost and reimbursement.
Regarding maternal vaccination- there is no issue with supply vs. demand here. Nirsevimab however is tougher. To help reduce costs, more birthing facilities are being enrolled in the VFC program to get nirsevimab.
Work Group proposes some options for a vaccine recommendation. Work group supports a broad recommendation for all college students (this seems like an obviously correct move- dorms are key factors for outbreaks). They also suggest a permissive recommendation for meningococcal B.
The Work Group will now present on their assessments of GSK's pentavalent meningococcal vaccine:
www.cdc.gov/vaccines...
The three vaccines caused similar reactogenicity, although unsolicited AEs slightly more common with pentavalent. No obvious safety issues are noted.
With regard to serious adverse events and deaths, these were very rare, and in general look to be unrelated. Deaths were not related to vaccination (literally look at the causes).
Pentavalent vaccine was non-inferior to ACWY except 1 dose for serogroup A which is rare.
For menB, menB vaccine was slightly better than pentavalent but unclear whether this has any clinical relevance. Work Group expresses some concern about durability of antibodies at 24 months. I do think GSK addressed this reasonably well though previously.
Because meningococcal disease is so rare and such a catastrophic illness, testing vaccines is focused on evaluating immune responses. Notably, people do carry the bacteria in their nasopharynx and so you can look at carriage rates pre-/post-vaccination to get a sense of effect.
GSK basically combined ACWY and B vaccines into one vaccine. Their trial was smaller than is typical for vaccine trials but given that it's for meningococcal this is not unreasonable. Generally the vaccine was well-tolerated with typical vaccine reactogenicity.
The vaccine was compared to the other meningococcal vaccines (because they are standard of care- you cannot ethically give placebo). In terms of immunogenicity, it seemed to outperform ACWY when given as 2 doses compared to those who never received ACWY.
With regard to menB (historically a difficult pathogen for the human immune system to respond to effectively- the polysaccharide capsule which is the immunogen for other serogroups is not immunogenic for B), the pentavalent vaccine performed similarly to the MenB vaccine.
