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ACKNOWLEDGMENTS
We thank A. P. Carter and R. Tan for helpful discussions, L. Nocka
for SEC-MALS experiments, B. LaFrance for MT image analysis
advice, P. Grob, and J. Atherton for MT processing in RELION,
D. Toso, J. Remis, and A. Chintangal for microscopy and
computational support, the QB3 Macrolab for competent cell lines
and TEV protease purification, the UC Berkeley Cell Culture Facility
for providing the insect cells, the Cal-Cryo facility at UC Berkeley
for EM imaging, and the Marconi100 for MD simulations.
Funding:This work was supported by grants from the National
Institute of General Medical Sciences (GM094522 (A.Y.),
GM123655-03 (L.F.), GM051487 (E.N.), GM127018 (E.N.), and the
National Science Foundation (MCB-1617028 and MCB-1055017,
A.Y.), PRACE (2019215144, MG), and Istanbul Technical
University BAP (MGA-2021-42803, MG). E.N. is a Howard
Hughes Medical Institute Investigator.Author contributions:
L.F., L.E., Q.F., E.N., and A.Y. conceived the project and analyzed
the data. L.F. and J.F. purified the proteins and performed
single-molecule experiments. Q.F. and L.E. performed cryo-EM
sample preparation, data collection, and analysis. Q.F., D.P.F,
and F.D. performed Rosetta modeling. A.J. performed stepping
measurements. M. Go. and M. Gu. performed MD simulations.
T.H. collected and analyzed data for K490. K.C. created
scientific illustrations. L.F., Q.F., L.E., M. Gur, E.N., and A.Y.
wrote the manuscript, with further edits from all authors.
Competing interests:The authors declare no competing
interests.Data and materials availability:All data are available
in data S1. Materials are available from A.Y. under a material
agreement with the University of California, Berkeley. The
coordinates for MAP7 bound to tubulin are available at the
Protein Data Bank (PDB) with accession code 7SGS. All cryo-EM
maps are available at the EMDB with accession codes
EMD-25120 (FL MAP7), EMD-25119 (MAP7-MTBD and FL tau),
EMD-25118 (MAP7 and kinesin), EMD-25117 (MAP783-134).

SUPPLEMENTARY MATERIALS
science.org/doi/10.1126/science.abf6154
Materials and Methods
Figs. S1 to S16
Tables S1 and S2
References ( 27 – 57 )
MDAR Reproducibility Checklist
Movies S1 to S6
Data S1

7 November 2020; resubmitted 28 July 2021
Accepted 8 December 2021
10.1126/science.abf6154

CORONAVIRUS

SARS-CoV-2 vaccine protection and deaths among

US veterans during 2021

Barbara A. Cohn^1 †, Piera M. Cirillo1,2†, Caitlin C. Murphy^3 †,

Nickilou Y. Krigbaum1,2, Arthur W. Wallace2,4*

We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine effectiveness against

infection (VE-I) and death (VE-D) by vaccine type in 780,225 veterans in the Veterans Health

Administration, covering 2.7% of the US population. From February to October 2021, VE-I declined for all

vaccine types, and the decline was greatest for the Janssen vaccine, resulting in a VE-I of 13.1%.

Although breakthrough infection increased risk of death, vaccination remained protective against death

in persons who became infected during the Delta variant surge. From July to October 2021, VE-D for

age <65 years was 73.0% for Janssen, 81.5% for Moderna, and 84.3% for Pfizer-BioNTech; VE-D for age

≥65 years was 52.2% for Janssen, 75.5% for Moderna, and 70.1% for Pfizer-BioNTech. Findings support

continued efforts to increase vaccination, booster campaigns, and multiple additional layers of

protection against infection.

T

he mRNA vaccines BNT162b2 (Pfizer-

BioNTech) and mRNA-1273 (Moderna)

and the viral vector vaccine JNJ-78436735

(Janssen) have effectively prevented

clinically recognized disease caused by

severe acute respiratory syndrome coronavirus

2 (SARS-CoV-2) since their rollout in the United

States in late 2020 ( 1 , 2 ). Vaccines have also

reduced the incidence of asymptomatic infec-

tion and associated infectivity ( 3 ). However,

by July 2021, the United States experienced a

surge in cases of COVID-19, dominated by the

B.1.617.2 (Delta) variant ( 4 , 5 ). Initial reports,

including follow-up of the Pfizer-BioNTech

and Moderna trials ( 6 – 8 ), suggested sustained

vaccine protection ( 9 ), but three reports by the

US Centers for Disease Control and Prevention

(CDC) in August 2021 ( 10 – 12 ) demonstrated

that protection against infection had declined

in mid-summer as the Delta variant rose to

dominance; protection against hospitaliza-

tion and death remained high ( 13 – 15 ). Break-

through infections, illness, hospitalizations,

and deaths have since continued to emerge

in vaccine recipients.

This phenomenon has been most compre-

hensively monitored in Israel, where high

levels of transmission of the Delta variant led

to a resurgent outbreak in mid-June 2021 ( 16 )

despite a successful nationwide campaign to

vaccinate the population ( 17 ). Israel author-

ized boosters of the Pfizer-BioNTech vac-

cine for adults age≥60 years in July 2021 and

extended this authorization to adults age

≥50 years in August 2021 ( 18 ). Rates of infec-

tion and severe illness subsequently declined

in those who received a booster ( 19 ). Largely

on the basis of these data, as well as data

from the UK ( 20 , 21 ), the US Food and Drug

Administration (FDA) authorized boosters

of the Pfizer-BioNTech vaccine for older (age

≥65 years) and higher-risk adults in September

2021 ( 22 ); the FDA similarly authorized boos-

ters of the Moderna vaccine in October 2021, as

well as boosters for all recipients of the Janssen

vaccine ( 23 ).

The debate over boosters in the United

States ( 24 ) has laid bare the limitations of

its public health infrastructure: National

data on vaccine breakthrough are inadequate.

The CDC transitioned in May 2021 from moni-

toring all breakthrough infections to focus on

identifying and investigating only hospitalized

or fatal cases attributable to any cause, includ-

ing causes not related to COVID-19 ( 25 ). Some

data on vaccinations, infections, and deaths

are collected through a patchwork of local

health departments ( 10 ), but these data are

frequently out of date and difficult to aggregate

at the national level. We addressed this gap

and examined SARS-CoV-2 infection and deaths

by vaccination status in 780,225 veterans during

the period 1 February 2021 to 1 October 2021,

encompassing the emergence and dominance

of the Delta variant in the United States.

The distribution of SARS-CoV-2 infection by

demographics, comorbidity, and vaccination

status is shown in table S1 for 1 February 2021

to 1 October 2021 (n= 780,225 subjects). The

percentage of polymerase chain reaction (PCR)

test positivity is higher in veterans who were

unvaccinated (25.8%), female (15.8%), Hispanic

(13.9%), American Indian/Alaska Native (14.7%)

or Native Hawaiian/Pacific Islander (14.2%),

age <50 years at time of reverse transcription

PCR (RT-PCR) assay (19.1%), and had a lower

comorbidity score (16.2% for Charlson Comor-

bidity Index = 0) ( 26 ); 33,514 positive PCR

SCIENCEscience.org 21 JANUARY 2022¥VOL 375 ISSUE 6578 331

(^1) Public Health Institute, Oakland, CA, USA. (^2) San Francisco
Veterans Affairs Medical Center, San Francisco, CA, USA.
(^3) School of Public Health, University of Texas Health Science
Center at Houston, Houston, TX, USA.^4 Department of
Anesthesiology and Perioperative Care, University of
California, San Francisco, San Francisco, CA, USA.
*Corresponding author. Email: [email protected]
†These authors contributed equally to this work.
RESEARCH | REPORTS