#160 - Paul Offit, MD: Latest on COVID-19 vaccines and their safety, herd immunity, & viral variants

KEYPOINTS

• 01

  Two vaccine platforms were in wide use by spring 2021

  The mRNA vaccines (Pfizer and Moderna) deliver instructions for the spike protein. The J&J vaccine uses a replication-defective adenovirus 26 vector, which had already been given to about 200,000 people in West Africa against Ebola. More than six million US doses of J&J had been given, and more than 20 million AstraZeneca doses in the UK and Europe. Russia's vaccine used Ad26 followed by Ad5. Offit traces the lineage back to cowpox in the late 1700s and Pasteur's killed rabies vaccine about 100 years later.

• 02

  Rare vaccine side effects show up within about six weeks

  Offit says serious vaccine side effects historically appear within weeks of a dose. Examples include narcolepsy from one adjuvanted 2009 pandemic flu vaccine (about 1 in 55,000) and Guillain-Barré after flu vaccine (about 1 per million). Others are vaccine-derived polio from Sabin's oral vaccine (about 1 per 2.4 million) and yellow-fever-like illness from the yellow fever vaccine (about 1 per million). That's why he discounts fears about '10 years of data' for mRNA, which cells translate into protein and can't reverse into DNA.

• 03

  Why HIV beat vaccine makers, and SARS-CoV-2 hasn't

  HIV mutates its surface glycoprotein again and again within a single infection, and it grows in T helper cells, the orchestrators of the immune system. Several billion dollars, including an adenovirus-vector vaccine that may have made things worse, failed to produce an HIV vaccine. SARS-CoV-2 mutates far more slowly, more like measles, whose 1960s vaccines still work 50 years later.

• 04

  Variants so far are close enough for current vaccines

  The original D614G strain killed about 570,000 Americans and is the target of every vaccine. B.1.1.7 (UK) is close enough to be covered. Offit watches whether a variant arises that natural or vaccine immunity can't touch, which would put us 'back to square one'. He thinks SARS-CoV-2 won't be a 'one and done' vaccine but needn't be yearly like flu.

• 05

  Sterilizing immunity is unlikely, but disease protection should last

  Viruses with short incubation periods, like this one, let infection get started before memory B and T cells can respond. Diseases like measles, with 10–14-day incubation, can be eliminated, as measles was in the US by 2000 and rubella by 2005. Offit expects antibody levels to fall over 6–18 months, while memory cells keep protecting against severe disease for a few years, not decades.

• 06

  Get the second mRNA dose

  One dose gives about 80% protection and two give 90–95%. Offit says the second dose also gives more complete immunity and more breadth against variants that have drifted from the original strain.

• 07

  Relative and absolute risk reduction were poorly communicated

  When J&J was authorized, headlines compared it with Pfizer's '96%' and Moderna's '95%' efficacy. In Pfizer's roughly 40,000-person trial there were about 165 cases among 20,000 placebo recipients versus 8 among vaccinated people, an absolute risk reduction of about 0.9%. J&J's absolute reduction was about 1.7% and Moderna's about 1.2%. By absolute measures, the 'weaker' J&J vaccine looked at least as good, and all three are great vaccines.

• 08

  The J&J pause was an overreaction that chilled confidence

  With about one case of cerebral venous sinus thrombosis per million doses, Offit estimates roughly 1,850 deaths prevented per million vaccinated. He understood the goal of warning doctors not to treat these clots with heparin, but believes the pause sent 'a chill' that would spill over to every COVID vaccine.

• 09

  Herd immunity needs about 80%, and hesitancy is the obstacle

  Offit estimates 22–30% of Americans had been infected and that about another 120 million people needed full vaccination. Surveys then showed about 30% of Christian evangelicals refusing, and about 14% of Black Americans saying they definitely wouldn't get vaccinated. He expected vaccines approved down to age 12 soon and to age 6 by early the next year.